884:
1749:
872:
436:
1641:
1794:
1948:. The procedure begins actually with redox chemistry at the protected phosphorus atom. A tricoordinate phosphorus, used on account of the high reactivity, is tagged with a cyanoethyl protecting group on a free oxygen. After the coupling step follows an oxidation to phosphate, whereby the protecting group stays attached. Free OH-groups, which did not react in the coupling step, are acetylated in an intermediate step. These additionally-introduced protecting groups then inhibit, that these OH-groups might couple in the next cycle.
1712:
396:
1808:
1422:
529:
236:
22:
1857:
157:
255:
1914:
1697:
1273:
389:
1265:
502:
858:
1952:
1895:
224:
regarding the reaction conditions such as reaction time, temperature and reagents can be standardized so that they are carried out by a machine, while yields of well over 99% can be achieved. Otherwise, the separation of the resulting mixture of reaction products is virtually impossible (see also
1477:
Many groups can suffice for the alcoholic component, and the specific cleaving conditions are contrariwise generally quite similar: each ester can be hydrolyzed in a basic water-alcohol solution. Instead, most ester protecting groups vary in how mildly they can be formed from the original acid.
3028:
András Lipták, János Imre, János
Harangi, Pál Nánási, András Neszmélyi: "Chemo-, stereo- and regioselective hydrogenolysis of carbohydrate benzylidene acetals. Synthesis of benzyl ethers of benzyl α-D-, methyl β-D-mannopyranosides and benzyl α-D-rhamnopyranoside by ring cleavage of benzylidene
1636:: the transformation of an alkene with a diene leads to a cyclic alkene, which is nevertheless similarly endangered by electrophilic attack as the original alkene. The cleavage of a protecting diene proceeds thermically, for the Diels-Alder reaction is a reversible (equilibrium) reaction.
3524:
John N. Haseltine, Maria Paz Cabal, Nathan B. Mantlo, Nobuharu
Iwasawa, Dennis S. Yamashita, Robert S. Coleman, Samuel J. Danishefsky, Gayle K. Schulte: "Total synthesis of calicheamicinone: new arrangements for actuation of the reductive cycloaromatization of aglycon congeners", in:
2281:
Morris J. Robins, Vicente Samano, Mark D. Johnson: "Nucleic acid-related compounds. 58. Periodinane oxidation, selective primary deprotection, and remarkably stereoselective reduction of tert-butyldimethylsilyl-protected ribonucleosides. Synthesis of 9-(β-D-xylofuranosyl)adenine or
1782:
does not employ protective groups. As an alternative, Baran presented a novel protective-group free synthesis of the compound hapalindole U. The previously published synthesis according to Baran, contained 20 steps with multiple protective group manipulations (two confirmed):
1310:
Cyclic acetals are very much more stable against acid hydrolysis than acyclic acetals. Consequently acyclic acetals are used practically only when a very mild cleavage is required or when two different protected carbonyl groups must be differentiated in their liberation.
147:
As a rule, the introduction of a protecting group is straightforward. The difficulties honestly lie in their stability and in selective removal. Apparent problems in synthesis strategies with protecting groups are rarely documented in the academic literature.
2757:
Karel F. Bernady, M. Brawner Floyd, John F. Poletto, Martin J. Weiss: "Prostaglandins and congeners. 20. Synthesis of prostaglandins via conjugate addition of lithium trans-1-alkenyltrialkylalanate reagents. A novel reagent for conjugate 1,4-additions", in:
1944:‑butyl group (acidic cleavage) and diverse protecting groups for functional groups on the amino acid side-chains are used. Up to four different protecting groups per nucleobase are used for the automated synthesis of DNA and RNA sequences in the
107:
Protecting groups are more common in small-scale laboratory work and initial development than in industrial production because they add additional steps and material costs. However, compounds with repetitive functional groups – generally,
1887:'s research group. Here 42 functional groups (39 hydroxyls, one diol, an amine group, and a carboxylic acid) required protection. These proceeded through 8 different protecting groups (a methyl ester, five acetals, 20 TBDMS esters, nine
3619:
Yves Rubin, Carolyn B. Knobler, Francois
Diederich: "Precursors to the cyclocarbons: from 3,4-dialkynyl-3-cyclobutene-1,2-diones and 3,4-dialkynyl-3-cyclobutene-1,2-diols to cyclobutenodehydroannulenes and higher oxides of carbon", in:
1759:
for deprotection of the right-side ester group is reduced and it stays intact. Significantly by placing the deuterium atoms next to the left-side ester group or by changing the wavelength to 254 nm the other monoarene is obtained.
2363:
Leo A. Paquette, Annette M. Doherty, Christopher M. Rayner: "Total synthesis of furanocembranolides. 1. Stereocontrolled preparation of key heterocyclic building blocks and assembly of a complete seco-pseudopterane framework", in:
4180:
Martin
Banwell, David Hockless, Bevyn Jarrott, Brian Kelly, Andrew Knill, Robert Longmore, Gregory Simpson: "Chemoenzymatic approaches to the decahydro-as-indacene cores associated with the spinosyn class of insecticide", in:
1689:) and subsequently reaction with chlorotrimethylsilane to a terminally TMS-protected alkyne. Cleavage follows hydrolytically – with potassium carbonate in methanol – or with fluoride ions like for example with
3000:
R.E. Ireland, D.W. Norbeck: "Convergent synthesis of polyether ionophore antibiotics: the synthesis of the monensin bis(tetrahydrofuran) via the
Claisen rearrangement of an ester enolate with a β-leaving group", in:
1244:
The most common protecting groups for carbonyls are acetals and typically cyclic acetals with diols. The runners-up used are also cyclic acetals with 1,2‑hydroxythiols or dithioglycols – the so-called
1676:
For alkynes there are in any case two types of protecting groups. For terminal alkynes it is sometimes important to mask the acidic hydrogen atom. This normally proceeds from deprotonation (via a strong base like
1769:
The use of protective groups is pervasive but not without criticism. In practical terms their use adds two steps (protection-deprotection sequence) to a synthesis, either or both of which can dramatically lower
341:; thus silicon protecting groups are almost invariably removed by fluoride ions. Each type of counterion, i.e. cleavage reagent, can also selectively cleave different silicon protecting groups depending on
524:
Aliphatic methyl ethers cleave with difficulty and only under drastic conditions, so that these are in general only used with quinonic phenols. However, hemiacetals and acetals are much easier to cleave.
91:
groups, and cannot be discouraged by any means. When an ester must be reduced in the presence of a carbonyl, hydride attack on the carbonyl must be prevented. One way to do so converts the carbonyl into an
4152:
Hideyuki Tanaka, Takashi
Kamikubo, Naoyuki Yoshida, Hideki Sakagami, Takahiko Taniguchi, Kunio Ogasawara: "Enantio- and Diastereocontrolled Synthesis of (−)-Iridolactone and (+)-Pedicularis-lactone", in:
698: — Comparable stability to MOM, MEM und SEM, but also admits reductive removal: sodium in liquid ammonia, catalytic hydrogenation (palladium hydroxide on activated carbon), or Raney nickel in ethanol
2138:
Tod K Jones, Robert A. Reamer, Richard
Desmond, Sander G. Mills: "Chemistry of tricarbonyl hemiketals and application of Evans technology to the total synthesis of the immunosuppressant (−)-FK-506", in:
2920:
Toshiyuki Kan, Masaru
Hashimoto, Mitsutoshi Yanagiya, Haruhisa Shirahama: "Effective deprotection of 2-(trimethylsilylethoxy)methylated alcohols (SEM ethers). Synthesis of thyrsiferyl-23 acetate", in:
4125:
Antonius J. H. Klunder, Jie Zhu, Binne
Zwanenburg: "The Concept of Transient Chirality in the Stereoselective Synthesis of Functionalized Cycloalkenes Applying the Retro-Diels-Alder Methodology", in:
2688:
Serge David, Annie
Thieffry, Alain Veyrières: "A mild procedure for the regiospecific benzylation and allylation of polyhydroxy-compounds via their stannylene derivatives in non-polar solvents", in:
3159:
Robert M. Williams, Peter J. Sinclair, Dongguan Zhai, Daimo Chen: "Practical asymmetric syntheses of α-amino acids through carbon-carbon bond constructions on electrophilic glycine templates", in:
1902:
The introduction or modification of a protecting group occasionally influences the reactivity of the whole molecule. For example, diagrammed below is an excerpt of the synthesis of an analogue of
1385:-acetals with acid catalysis from a dithiol and the carbonyl compound. Because of the greater stability of thioacetals, the equilibirum lies on the side of the acetal. In contradistinction to the
761: — More labile than MEM and MOM to acid hydrolysis: 0.1 M hydrochloric acid in methanol, concentrated hydrofluoric acid in acetonitrile, boron trifluoride etherate in dichloromethane, or
3862:
Tainejiro Hiyama, Akihiro Kanakura, Hajime Yamamoto, Hitosi Nozaki: "General Route to α,β-unsaturated Aldehydes of Homoterpenoid and terpenoid Structure. Sythesis of JH-II and β-Sinensal", in:
1411:-acetals. Their formation follows analogously from the thioalcohol. Also their cleavage proceeds under similar conditions and predominantly through mercury(II) compounds in wet acetonitrile.
3377:
Juji Yoshimura, Shigeomi Horito, Hiroriobu Hashimoto: "Facile Synthesis of 2,3,4,6-Tetra-O-benzyl-D-glucopyranosylidene Acetals Using Trimethylsilyl Trifluoromethanesulfonate Catalyst", in:
766:
2730:
Paul A. Wender, Carlos R. D. Correia: "Intramolecular photoinduced diene-diene cyaloadditions: a selective method for the synthesis of complex eight-membered rings and polyquinanes", in:
758:
3497:
Samuel J. Danishefsky, Nathan B. Mantlo, Dennis S. Yamashita, Gayle. Schulte: "Concise route to the calichemicin-esperamicin series: the crystal structure of an aglycone prototype", in:
3565:
Peter Mohr, Nada Waespe-Šarčević, Christoph Tamm, Krystyna Gawronska, Jacek K. Gawronski: "A Study of Stereoselective Hydrolysis of Symmetrical Diesters with Pig Liver Esterase", in:
864:
An exceptional case appears with the benzylideneprotecting group,which also admits reductive cleavage. This proceeds either through catalytic hydrogenation or with the hydride donor
4009:
Timothy S. Butcher, Feng Zhou, Michael R. Detty: "Debrominations of vic-Dibromides with Diorganotellurides. 1. Stereoselectivity, Relative Rates, and Mechanistic Implications", in:
2467:
M.L. García, J. Pascual, L. Borràs, J.A. Andreu, E. Fos, D. Mauleón, G. Carganico, F. Arcamone: "Synthesis of new ether glycerophospholipids structurally related to modulator", in:
2947:
Joseph P. Marino, Scott L. Dax: "An efficient desilylation method for the generation of o-quinone methides: application to the synthesis of (+)- and (−)-hexahydrocannabinol", in:
3955:
Ahmed M. Tafesh, Jens Weiguny: "A Review of the Selective Catalytic Reduction of Aromatic Nitro Compounds into Aromatic Amines, Isocyanates, Carbamates, and Ureas Using CO", in:
609:-Butyldimethylsilyl (TBDMS or TBS) — Cleaved with acetic acid in tetrahydrofuran/water, Pyridinium tosylate in methanol, trifluoroacetic acid in water, hydrofluoric acid in
4522:
Synthetic studies of marine alkaloids hapalindoles. Part 2. Lithium aluminum hydride reduction of the electron-rich carbon-carbon double bond conjugated with the indole nucleus
3674:
G. Bauduin, D. Bondon, Y. Pietrasanta, B. Pucci: "Reactions de transcetalisation – II: Influence des facteurs steriques et electroniques sur les energies de cetalisation", in:
2446:
220:
A common example for this application, the Fmoc peptide synthesis, in which peptides are grown in solution and on solid phase, is very important. The protecting groups in
213:-butyl ether on the phenol group. The benzyl ester can be removed by hydrogenolysis, the fluorenylmethylenoxy group (Fmoc) by bases (such as piperidine), and the phenolic
1280:
Overall, trans-acetalation plays a lesser role in forming protective acetals; they are formed as a rule from glycols through dehydration. Normally a simple glycol like
2547:
H. Nagaoka, W. Rutsch, G. Schmidt, H. Ito, M.R. Johnson, Y. Kishi: "Total synthesis of rifamycins. 1. Stereocontrolled synthesis of the aliphatic building block", in:
1932:
Protecting group chemistry finds itself an important application in the automated synthesis of peptides and nucleosides. The technique was introduced in the field of
3728:
M.P. Bosch, M. Pilar Bosch, Francisco Camps, Jose Coll, Angel Guerrero, Toshio Tatsuoka, Jerrold Meinwald: "A stereoselective total synthesis of (±)-muzigadial", in:
4100:
3431:
Kwan Soo Kim, Yang Heon Song, Bong Ho Lee, Chi Sun Hahn: "Efficient and selective cleavage of acetals and ketals using ferric chloride adsorbed on silica gel", in:
4349:
Rosa F. Lockwood, Kenneth M. Nicholas: "Transition metal-stabilized carbenium ions as synthetic intermediates. I. α- carbenium ions as propargylating agents", in:
1073:
695:
235:
868:(DIBAL). The cleavage with DIBAL deprotects one alcohol group, for the benzyl moiety stays as a benzyl ether on the second, sterically hindered hydroxy group.
1748:
3781:
Ulrich Schmidt, Thomas Beuttler, Albrecht Lieberknecht, Helmut Griesser: "Aminosäuren und peptide – XXXXII. Synthese von Chlamydocin + epi-Chlamydocin", in:
1418:
ions is shown below. Here it is applied, that aldehydes are very much more activated carbonyls than ketones and that many addition reactions are reversible.
1211:
592:
3982:
Evan L. Allred, Boyd R. Beck, Kent J. Voorhees: "Formation of carbon-carbon double bonds by the reaction of vicinal dihalides with sodium in ammonia", in:
851:
630:‑Butyldiphenylsilyl (TBDPS) — Similar conditions to TBS but even longer reaction times (100–250× slower than TBS and 5–10× slower than TIPS)
4742:
4063:
Corrado Malanga, Serena Mannucci, Luciano Lardicci: "Carbon-halogen bond activation by nickel catalyst: Synthesis of alkenes, from 1,2-dihalides", in:
3592:
Théophile Tschamber, Nada Waespe-Šarčević, Christoph Tamm: "Stereocontrolled Synthesis of an Epimer of the C(19)-to-C(27) Segment of Rifamycin S", in:
847:
4443:
Baran, Phil S.; Maimone, Thomas J.; Richter, Jeremy M. (22 March 2007). "Total synthesis of marine natural products without using protecting groups".
1225:
1198:
4804:
2785:
Elias J. Corey, Haruki Niwa, Jochen Knolle: "Total synthesis of (S)-12-hydroxy-5,8,14-cis,-10-trans-eicosatetraenoic acid (Samuelsson's HETE)", in:
273:
exhibit very similar reactivities, a transformation that protects or deprotects a single hydroxy group must be possible for a successful synthesis.
490:
486:
281:
Many reaction conditions have been established that will cleave protecting groups. One can roughly distinguish between the following environments:
1285:
1010:
352:
2193:
David A. Evans, Stephen W. Kaldor, Todd K. Jones, Jon Clardy, Thomas J. Stout: "Total synthesis of the macrolide antibiotic cytovaricin", in:
3274:
Festphasensynthese eines tumorassoziierten Sialyl-Tn-Antigen-Glycopeptids mit einer Partialsequenz aus dem "Tandem Repeat" des MUC-1-Mucins
3404:
Bruce H. Lipshutz, Daniel Pollart, Joseph Monforte, Hiyoshizo Kotsuki: "Pd(II)-catalyzed acetal/ketal hydrolysis/exchange reactions", in:
3064:
James A. Marshall, Joseph D. Trometer, Bruce E. Blough, Thomas D. Crute: "Stereochemistry of SN2' additions to acyclic vinyloxiranes", in
807:
Methyl ethers – Cleavage is by TMSI in dichloromethane or acetonitrile or chloroform. An alternative method to cleave methyl ethers is BBr
4815:
A user site excerpting the classic Greene and Wuts text regarding stability of a few key groups, from this reference's extensive tables.
1342:, which one begins with to form these acetals, have a very unpleasant stench and are poisonous, which severely limit their applications.
1167:
71:, specific parts of the molecules cannot survive the required reagents or chemical environments. These parts (functional groups) must be
2711:
Kaoru Fuji, Shigetoshi Nakano, Eiichi Fujita: "An Improved Method for Methoxymethylation of Alcohols under Mild Acidic Conditions", in:
205:
is a strategy allowing the specific deprotection of one protective group in a multiply-protected structure. For example, the amino acid
2309:
R. Roger F. Newton, Derek P. Reynolds, Colin F. Webb, Stanley M. Roberts: "A short and efficient total synthesis of (±) prostaglandin D
254:
4829:
4654:
Merrifield, R. B.; Barany, G.; Cosand, W. L.; Engelhard, M.; Mojsov, S. (1977). "Proceedings of the 5th American Peptide Symposium".
1654:
1108:
686:
661:
2417:
Michel Bessodes, Dimitri Komiotis, Kostas Antonakis: "Rapid and selective detritylation of primary alcohols using formic acid", in:
830:) present for protecting-group chemistry a special class of alcohols. One can exploit the adjacency of two hydroxy groups, e.g. in
3186:
Glenn L. Stahl, Roderich Walter, Clarck W. Smith: "General procedure for the synthesis of mono-N-acylated 1,6-diaminohexanes", in:
2628:
W. Clark Still, Shizuaki Murata, Gilbert Revial, Kazuo Yoshihara: "Synthesis of the cytotoxic germacranolide eucannabinolide", in:
100:
for the carbonyl. After the hydride step is complete, aqueous acid removes the acetal, restoring the carbonyl. This step is called
3647:
Sunggak Kim, Yong Gil Kim, Deog-il Kim: "A novel method for selective dioxolanation of ketones in the presence of aldehydes", in:
2220:
James A. Marshall, Richard Sedrani: "A convergent, highly stereoselective synthesis of a C-11-C-21 subunit of the macbecins", in:
685:, (DMT) — Removed by weak acid. DMT group is widely used for protection of 5'-hydroxy group in nucleosides, particularly in
1827:
Although the use of protecting groups is not preferred in industrial syntheses, they are still used in industrial contexts, e.g.
1288:
is used for acetalation.Modern variants also use glycols, but with the hydroxyl hydrogens replaced with a trimethylsilyl group.
4693:
Serge L. Beaucage, Radhakrishman P. Iyer: "Advances in the Synthesis of Oligonucleotides by the Phosphoramidite Approach", in:
1130:
1023:
345:. The advantage of fluoride-labile protecting groups is that no other protecting group is attacked by the cleavage conditions.
4036:
C. J. Li, David N. Harpp: "Bis(triphenylstanyl)telluride a mild and selective reagent for telluration and debromination", in:
2170:-Di-O-methylelaiophylidene – preparation from elaiophylin and total synthesis from (R)-3-hydroxybutyrate and (S)-malate", in:
1621:‑1,2‑dibromoalkane: the regeneration of the alkene then follows with preservation of conformation via elemental
4268:
Barry J. Teobald: "The Nicholas reaction: the use of dicobalt hexacarbonyl-stabilised propargylic cations in synthesis", in:
4226:
2038:
1982:
4090:
Byung Woo Yoo, Seo Hee Kim, Jun Ho Kim: "A Mild, Efficient, and Selective Debromination of vic-Dibromides to Alkenes with Cp
359:(30–40 °C). Because enzymes have very high substrate specificity, the method is quite rare, but extremely attractive.
1362:-acetals, very much stabler against acid hydrolysis. This enables the selective cleavage of the latter in the presence of
2893:
Steven D. Burke, Gregory J. Pacofsky: "The ester enolate claisen rearrangement. Total synthesis of (±)-ethisolide", in:
209:
could be protected as a benzyl ester on the carboxyl group, a fluorenylmethylenoxy carbamate on the amine group, and a
1582:– Removed by strong hot acid (pH < 1, T > 100 °C) or alkali (pH > 12, T > 100 °C), but not e.g.
1560:
Allyl esters — As with allyl ethers, also removed by diverse platinum complexes – connected with acid workup
2494:
Yuji Oikawa, Tadao Yoshioka, Osamu Yonemitsu: "Specific removal of o-methoxybenzyl protection by DDQ oxidation", in:
2166:
Dieter Seebach, Hak-Fun Chow, Richard F.W. Jackson, Marius A. Sutter, Suvit Thaisrivongs, Jürg Zimmermann: "(+)-11,11
563:(Piv) – Removed by acid, base or reductant agents. It is substantially more stable than other acyl protecting groups.
4626:
J.M. McClure, Samuel J. Danishefsky: "A novel Heck arylation reaction: rapid access to congeners of FR 900482", in:
970:
or Birch reduction, but have a decided drawback relative to the carbamates or amides: they retain a basic nitrogen.
2866:
Robert C. Gadwood, Renee M. Lett, Jane E. Wissinger: "Total synthesis of (±)-poitediol and (±)4-epipoitediol", in:
1605:
Alkenes rarely need protection or are protected. They are as a rule only involved in undesired side reactions with
1393:‑acetal case, it is not needed to remove water from the reaction mixture in order to shift the equilibrium.
493:, for these exhibit differential removal. Sterically hindered esters are less susceptible to nucleophilic attack:
3213:
Naomi Sakai, Yasufumi Ohfune: "Total synthesis of galantin I. Acid-catalyzed cyclization of galantinic acid", in:
3889:
F. Huet, A. Lechevallier, M. Pellet, J.M. Conia: "Wet Silica Gel; A Convenient Reagent for Deacetalization", in:
3808:
Elias J. Corey, Plato A. Magriotis: "Total synthesis and absolute configuration of 7,20-diisocyanoadociane", in:
1940:
in 1977. For peptide synthesis via automated machine, the orthogonality of the Fmoc group (basic cleavage), the
4825:
1291:
Acetals can be removed in acidic aqueous conditions. For those ends, the mineral acids are appropriate acids.
883:
4772:
4322:
Richard E. Connor, Kenneth M. Nicholas: "Isolation, characterization, and stability of α- carbonium ions", in:
4183:
2690:
2315:
707:
428:, which is activated through radiation with an appropriate wavelength and so can be removed. For examples the
1917:
Part of the synthesis of an analogue of Mitomycin C with modified reactivity through protecting-group exchange
4805:
A further set of study notes in tutorial form, with guidance and comments, from Profs. Grossman and Cammers.
1724:
1068:
1034:
4847:
1835:
1690:
1554:
1232:
865:
762:
614:
382:
3290:
1891:‑methoxybenzyl ethers, four benzoates, a methyl hemiacetal, an acetone acetal and an SEM ester).
783:
442:
The rare double-layer protecting group is a protected protecting group, which exemplify high stability.
4852:
4820:
3350:
T. Tsunoda, M. Suzuki, R. Noyori: "A facile procedure for acetalization under aprotic conditions", in:
1739:
804:
in methanol, palladium on activated carbon, or diverse platinum complexes – conjoined with acid workup.
373:
Only a few protecting groups can be detached oxidatively: the methoxybenzyl ethers, which oxidize to a
133:
4548:
Synthetic studies of marine alkaloids hapalindoles. Part 3 Total synthesis of (±)-hapalindoles H and U
4496:
Synthetic studies of marine alkaloids hapalindoles. Part I Total synthesis of (±)-hapalindoles J and M
2812:
Elias J. Corey, Mark G. Bock: "Protection of primary hydroxyl groups as methylthiomethyl ethers", in:
1921:
The exchange of a protecting group from a methyl ether to a MOM-ether inhibits here the opening of an
514:
4708:
4372:
K.M. Nicholas, R. Pettit: "On the stability of α-(alkynyl)dicobalt hexacarbonyl carbonium ions", in:
4360:
4337:
4310:
4283:
4078:
4051:
3877:
3796:
3662:
3419:
3365:
3121:
2935:
2908:
2827:
2509:
2482:
2432:
1945:
1876:
1583:
752:
618:
76:
4799:
4387:
4113:
3689:
3052:
2839:
Elias J. Corey, Duy H. Hua, Bai Chuan Pan, Steven P. Seitz: "Total synthesis of aplasmomycin", in:
2336:
Kyriacos C. Nicolaou, R. A. Daines, T. K. Chakraborty: "Total synthesis of amphoteronolide B", in:
917:. These characteristics imply that new protecting groups for amines are always under development.
517:
byproduct. The trimethylsilyl ethers are also extremely sensitive to acid hydrolysis (for example
4241:
Wenzel E. Davidsohn, Malcolm C. Henry: "Organometallic Acetylenes of the Main Groups III–V", in:
4218:
4214:
4207:
2030:
1937:
1678:
1546:
967:
3318:
Moussa, Ziad; D. Romo (2006). "Mild deprotection of primary N-(p-toluenesufonyl) amides with SmI
2066:
Michael Schelhaas, Herbert Waldmann: "Schutzgruppenstrategien in der organischen Synthese", in:
1997:
Michael Schelhaas, Herbert Waldmann: "Schutzgruppenstrategien in der organischen Synthese", in:
946:, which admit reductive cleavage, and the trifluoroacetamides, which hydrolyze easily in base.
939:-butoxycarbonyl, benzoxycarbonyl, fluorenylmethylenoxycarbonyl, and allyloxycarbonyl compounds.
4617:, 4th Ed., John Wiley & Sons Inc., Hoboken, New Jersey, pp. 10–13; ISBN 0-471-69754-0.
1865:
1845:
An important example of industrial applications of protecting group theory is the synthesis of
1743:
1296:
1053:
733:
378:
3835:
Elias J. Corey, Kyriacos C. Nicolaou, Takeshi Toru: "Total synthesis of (±)-vermiculine", in:
1441:– Removed by acid. Normally, the cleavage of acyclic acetals is easier than of cyclic acetals.
1133:(trichloroethyl chloroformate ) group – Removed by Zn insertion in the presence of acetic acid
674:‑Dimethoxybenzyl ether — Removed via oxidation with DDQ or ceric ammonium chloride
521:
suffices as a proton donator) and are consequently rarely used nowadays as protecting groups.
4550:
4524:
4498:
2181:
1832:
1705:
1704:
In order to protect the triple bond itself, sometimes a transition metal-alkyne complex with
1696:
1626:
1590:
510:
221:
2313:
methyl ester involving a new method for the cleavage of a dimethyl-t-butylsilyl ether", in:
1295:
is a common cosolvent, used to promote dissolution. For a non-acidic cleavage technique, a
624:
Triisopropylsilyl (TIPS) ethers) — Similar conditions to TBS but longer reaction times.
4760:
4588:
4573:
T. Reichstein, A. Grüssner: "Eine ergiebige Synthese der L-Ascorbinsäure (C-Vitamin)", in:
4454:
3607:
3580:
3254:
2081:
2012:
1779:
1633:
1518:
1470:
are the esters of various alcohols. Occasionally, esters are protected as ortho-esters or
1156:
741:
871:
8:
4374:
4324:
3891:
2713:
2095:
1735:
1179:
1171:
717:
583:
84:
61:
4458:
334:
Various groups are cleaved in acid or base conditions, but the others are more unusual.
4478:
2674:
2657:
2172:
2093:
V.N. Rajasekharan Pillai: "Photoremovable Protecting Groups in Organic Synthesis", in:
1907:
1850:
1494:
1414:
For aldehydes, a temporary protection of the carbonyl group the presence of ketones as
1300:
575:
241:
Schematic diagram of a solid-state peptide synthesis with orthogonal protecting groups
4562:
4536:
4510:
4401:
1872:
and then deprotected after the oxidation of the primary alcohols to carboxylic acids.
595: — 10–100× stabler than a TMS group. Cleaved with trifluoroacetic acid in water/
4814:
4747:
4667:
4628:
4470:
4425:
4351:
4297:
4222:
4038:
3915:
3864:
3837:
3810:
3783:
3703:
3649:
3622:
3527:
3499:
3406:
3352:
3215:
3161:
3108:
3003:
2922:
2895:
2868:
2841:
2814:
2787:
2732:
2630:
2603:
2549:
2496:
2419:
2366:
2338:
2256:
2195:
2141:
2068:
2034:
1999:
1978:
1933:
1686:
1531:
1498:
1049:
906:
723:
702:
600:
2658:"Metabolism of 3,4-dimethoxycinnamyl alcohol and derivatives by Coriolus versicolor"
1793:
1338:-acetals also have an application, albeit scant, as carbonyl protecting groups too.
751:
Tris(isopropyl)silyloxymethyl (TOM) — Commonly protects 2'-hydroxy function in
4724:
4663:
4604:, VCH Verlagsgesellschaft mbH, Weinheim 1996, pp. 711–729, ISBN 3-527-29284-5.
4575:
4558:
4532:
4506:
4482:
4462:
4445:
4417:
3923:
3594:
3567:
3333:
2699:
2669:
2324:
1728:
1594:
1004:
787:
356:
342:
309:
125:
68:
57:
53:
4794:
4641:
4256:
3997:
3928:
3910:
3850:
3823:
3743:
3716:
3635:
3540:
3512:
3446:
3392:
3228:
3201:
3174:
3077:
3016:
2962:
2881:
2854:
2800:
2773:
2745:
2643:
2616:
2589:
2562:
2379:
2351:
2297:
2269:
2235:
2208:
2154:
1467:
1281:
843:
814:
682:
596:
117:
25:
660:(PMB) — Removed by acid, hydrogenolysis, or oxidation – commonly with
4738:, 4th Ed., John Wiley & Sons Inc., Hoboken, New Jersey, ISBN 0-471-69754-0.
1775:
1771:
1613:
or catalytic hydration. For alkenes two protecting groups are basically known:
1567:
1403:-Acetals are hydrolyzed a factor of 10,000 times faster than the corresponding
1215:
1205:
1193:
1017:
992:
932:
745:
642:
571:
505:
Trimethylsilyl chloride, activated with imidazole, protects a secondary alcohol
464:
324:
270:
195:
183:
1807:
1774:. Crucially, added complexity impedes the use of synthetic total synthesis in
1640:
509:
Triorganosilyl sources have quite variable prices, and the most economical is
395:
4841:
4809:
4767:
4168:
4140:
4024:
4011:
3984:
3970:
3730:
3433:
3188:
2949:
2760:
2576:
2284:
2222:
1884:
1846:
1756:
1732:
1711:
1610:
1064:
988:
548:
482:
406:
363:
137:
1509:‑dimethylformamide, or methanol and catalytic trimethylsilyl chloride
21:
4781:
4474:
4429:
4402:"Isotope Effects in Photochemistry: Application to Chromatic Orthogonality"
4192:
2601:
Masahiro Hirama, Mitsuko Uei: "A chiral total synthesis of compactin", in:
1787:
Protected and unprotected syntheses of the marine alkaloid, hapalindole U.
1682:
1606:
839:
720:(MOM) — Removed by 6 M hydrochloric acid in tetrahydrofuran/water
711:
701:
Ethoxyethyl ethers (EE) – Cleavage more trivial than simple ethers e.g. 1N
610:
374:
367:
266:
4557:, Pages 6351–6360 Hideaki Muratake, Harumi Kumagami and Mitsutaka Natsume
3337:
1856:
4695:
4270:
4205:
Clayden, Jonathan; Greeves, Nick; Warren, Stuart; Wothers, Peter (2000).
4065:
3701:
John E. McMurry, Stephen J. Isser: "Total synthesis of longifolene", in:
3676:
3379:
3039:
2469:
2251:
1903:
1839:
1573:
1538:
1124:
1029:(Boc) group — Removed by concentrated strong acid (such as HCl or CF
943:
920:
914:
910:
793:
737:
579:
467:
460:
425:
410:
402:
291:
175:
156:
141:
109:
16:
Group of atoms introduced into a compound to prevent subsequent reactions
4466:
962:‑sulfonylamides,which are far too stable with aliphatic amines.
4409:
4243:
4155:
4127:
3957:
1811:
1530:
esters – Also removed by acid and some reductants. Can be formed from
1524:
1448:
1415:
1343:
1304:
1175:
1060:
1045:
518:
435:
414:
121:
4421:
1421:
265:
A further important example of orthogonal protecting groups occurs in
124:– may require protecting groups to order their assembly. Also, cheap
3909:
Romanski, J.; Nowak, P.; Kosinski, K.; Jurczak, J. (September 2012).
1880:
1828:
1579:
1471:
1000:
982:
955:
928:
924:
654:
315:
160:
Orthogonal protection of L-Tyrosine (Protecting groups are marked in
4800:
Senior undergraduate study notes on this subject, from Prof. Rizzo.
1913:
260:
Fmoc solid state peptide synthesis with orthogonal protecting groups
4731:, 1st ed., Georg Thieme Verlag, Stuttgart 1994, ISBN 3-13-135601-4.
1926:
1542:
1454:
1264:
1112:
1076:
group — Removed with complexes of metals like palladium(0) or
996:
587:
560:
481:
The most important esters with common protecting-group use are the
388:
297:
206:
88:
4295:
Kenneth M. Nicholas, R. Pettit: "An alkyne protection group", in:
3259:(PDF; 663 kB) In: Michael W. Pennington, Ben M. Dunn (eds.):
1972:
1272:
321:
Protecting groups cleaved by heavy metal salts or their complexes.
217:-butyl ether cleaved with acids (e.g. with trifluoroacetic acid).
96:, which does not react with hydrides. The acetal is then called a
3911:"High-pressure transesterification of sterically hindered esters"
3324:
1922:
1875:
A very spectacular example application of protecting groups from
1869:
1653:
2-cyanoethyl – removed by mild base. The group is widely used in
1292:
1152:
1120:
1116:
1098:
951:
888:
554:
501:
418:
338:
113:
60:
in a subsequent chemical reaction. It plays an important role in
2574:
W. Clark Still, Dominick Mobilio: "Synthesis of asperdiol", in:
1708:
is used. The release of the cobalt then follows from oxidation.
4653:
1951:
1660:
1512:
1490:
1487:
1444:
1434:
1363:
1189:
1148:
1088:
1077:
947:
835:
834:, in that one protects both hydroxy groups codependently as an
831:
827:
710:(MEM) — Removed by hydrobromic acid in tetrahydrofuran or
651:(triphenylmethyl, Tr) — Removed by acid and hydrogenolysis
648:
638:
544:
471:
348:
303:
93:
33:
29:
4795:
Introduction of protecting group and mechanism of deprotection
958: — verily any aza-heterocycle — admit protection as
726:(THP) — Removed by acetic acid in tetrahydrofuran/water,
4745:: "Schutzgruppenstrategien in der organischen Synthese", in:
1864:
In order to prevent oxidation of the secondary alcohols with
1798:
1563:
1438:
1339:
1163:
1136:
857:
801:
475:
456:
80:
37:
4684:. Reprint 2004, Oxford University Press, ISBN 0-19-963724-5.
3908:
1894:
645:. Bn group is widely used in sugar and nucleoside chemistry.
52:
is introduced into a molecule by chemical modification of a
4204:
1622:
1041:
285:
3759:, Ferdinand Enke Verlag, Stuttgart 1965, pp. 127–133.
1557:-catalyzed high-pressure methanolysis at room temperature.
692:
Methoxytrityl (MMT) – Removed by acid and hydrogenolysis.
557:(Bz) – Removed by acid or base, more stable than Ac group.
528:
4602:
Classics in Total Synthesis: Targets, Strategies, Methods
4531:, Pages 6343–6350 Hideaki Muratake and Mitsutaka Natsume
4505:, Pages 6331–6342 Hideaki Muratake and Mitsutaka Natsume
2250:
James D. White, Motoji Kawasaki: "Total synthesis of (+)-
3263:
volume 35, 1995, ISBN 978-0-89603-273-6, pp. 17–27.
474:, deprotected by weak acids. In rarer cases, a carbon
1127:. Too stable to readily remove from aliphatic amides.
1814:'s protecting-group free synthesis, reported in 2007.
1497:. Can be formed from diazomethane in diethyl ether,
1044:) group — Removed by base, such as 20–50 %
786:(tBu) – Removed with anhydrous trifluoroacetic acid,
1671:
1461:
4442:
1752:
Orthogonal protection Application in Photochemistry
1033:COOH), or by heating to >80 °C. Common in
497:
Chloroacetyl > acetyl > benzoyl > pivaloyl
79:is a highly reactive reagent that usefully reduces
4206:
3104:An Exceptionally Mild Deprotection of Phthalimides
2246:
2244:
1576:– Converted to standard ester by mild aqueous acid
1534:: isobutene in dioxane and catalytic sulfuric acid
1521:esters — Same as benzyl, but easier to cleave
780:-Methoxyphenyl ether (PMP) – Removed by oxidation.
617:in THF. Commonly protects 2'-hydroxy function in
1139:(Ts) group – Removed by concentrated acid (HBr, H
966:‑benzylated amines can be removed through
455:The classical protecting groups for alcohols are
4839:
4831:Schutzgruppen in der organischen Synthesechemie
3280:volume 109, 1997, pp. 629–631 (in German).
2655:
2241:
4736:Green's Protective Groups in Organic Synthesis
4615:Green's Protective Groups in Organic Synthesis
4400:Blanc, Aurélien; Bochet, Christian G. (2007).
3102:John O. Osby, Michael G. Martin, Bruce Ganem:
1647:
470:, deprotected by acids and fluoride ions; and
370:: ethers, esters, urethanes, carbonates, etc.
40:reduction, vs. unprotected reduction to a diol
3317:
1973:Theodora W. Greene; Peter G. M. Wuts (1999).
1731:orthogonal deprotection is demonstrated in a
1515:esters — Also removed by hydrogenolysis.
1457:– Removed by metal salts or oxidizing agents.
1377:-acetals normally follows analogously to the
1239:
1119:. Removed by base, often aqueous or gaseous
790:in acetic acid, or 4 N hydrochloric acid
1747:
1307:can be performed with workup in chloroform.
942:Other, more exotic amine protectors are the
527:
450:
434:
394:
387:
226:
4399:
1860:The Reichstein synthesis (of ascorbic acid)
931:. When a carbamate deprotects, it evolves
599:, acetic acid in water/tetrahydrofuran, or
445:
2282:3'-deuterioadenosine from adenosine", in:
1868:, they are protected via acetalation with
1822:
878:
613:, pyridinium fluoride in tetrahydrofuran,
276:
3927:
2673:
2024:
1617:Temporary halogenation with bromine to a
1466:The most important protecting groups for
1007:, or lithium or sodium in liquid ammonia.
985:group – Removed by acid and mild heating.
935:. The commonest-used carbamates are the
4766:Krzysztof Jarowicki, Philip Kocieński: "
1950:
1912:
1893:
1855:
1806:
1797:Hideaki Muratake's 1990 synthesis using
1792:
1271:
1263:
882:
730:‑toluenesulfonic acid in methanol
500:
432:-nitrobenzylgroup ought be listed here.
421:(resp. amine) hydrolyzes in light acid.
337:Fluoride ions form very strong bonds to
155:
151:
20:
2025:Chan, Weng C.; White, Peter D. (2004).
1428:
4840:
4674:
1975:Protecting Groups in Organic Synthesis
1663:(Me) – removed by strong nucleophiles
4734:Peter G.M. Wuts, Theodora W. Greene:
4613:Peter G.M. Wuts, Theodora W. Greene:
1178:or other soft thiol nucleophiles, or
759:β‑(Trimethylsilyl)ethoxymethyl
424:Photolabile protecting groups bear a
3256:Methods for Removing the Fmoc Group.
1481:
905:Amines have a special importance in
547:(Ac) – Removed by acid or base (see
409:to a vinyl group in the presence of
3292:Fmoc Solid Phase Peptide Synthesis.
2656:Kamaya, Yasushi; T Higuchi (2006).
2018:
1955:Automatic oligonucleotide synthesis
1595:Grignard (organomagnesium) reagents
1299:acetonitrile complex in acetone or
838:. Common in this situation are the
767:Hexamethyl phosphoric acid triamide
351:and other enzymes cleave ethers at
13:
4718:
4682:Fmoc Solid Phase Peptide Synthesis
3242:Fmoc Solid Phase Peptide Synthesis
2675:10.1111/j.1574-6968.1984.tb01309.x
2055:Fmoc Solid Phase Peptide Synthesis
2027:Fmoc Solid Phase Peptide Synthesis
1801:protecting groups (shown in blue).
1710:
1695:
1639:
1566:esters – Also removed by base and
1420:
895:-butyloxycarbonyl group is marked
870:
856:
14:
4864:
4788:
4709:doi:10.1016/S0040-4020(01)88752-4
4361:doi:10.1016/S0040-4039(01)83455-9
4338:doi:10.1016/S0022-328X(00)89454-1
4311:doi:10.1016/S0040-4039(01)97209-0
4284:doi:10.1016/S0040-4020(02)00315-0
4079:doi:10.1016/S0040-4020(97)10203-4
4052:doi:10.1016/S0040-4039(00)97045-X
3878:doi:10.1016/S0040-4039(01)94936-6
3797:doi:10.1016/S0040-4039(00)88171-X
3663:doi:10.1016/S0040-4039(00)92243-3
3420:doi:10.1016/S0040-4039(00)89114-5
3366:doi:10.1016/S0040-4039(00)74575-8
3322:following trifluoroacetylation".
3122:doi:10.1016/S0040-4039(01)81169-2
2936:doi:10.1016/S0040-4039(00)82883-X
2909:doi:10.1016/S0040-4039(00)85501-X
2828:doi:10.1016/S0040-4039(00)91422-9
2510:doi:10.1016/S0040-4039(00)86974-9
2483:doi:10.1016/S0040-4020(01)96051-X
2433:doi:10.1016/S0040-4039(00)84045-9
1672:Terminal alkyne protecting groups
1462:Carboxylic acid protecting groups
1016:(Moz or MeOZ) group – Removed by
67:In many preparations of delicate
4687:
4647:
4620:
4607:
4594:
4567:
4541:
4515:
4489:
4436:
4393:
4388:doi:10.1016/0022-328X(72)80037-8
4366:
4343:
4114:doi:10.5012/bkcs.2010.31.10.2757
3690:doi:10.1016/0040-4020(78)80243-9
3053:doi:10.1016/0040-4020(82)80083-5
1537:2,6‑Dialkylphenols (e.g.
1493: — Also removed by acid or
1147:) & strong reducing agents (
1107:) groups — common in
923:are primarily protected through
330:Double-layered protecting groups
269:chemistry. As carbohydrates or
253:
234:
194:-butyl ether protected phenolic
4316:
4289:
4262:
4235:
4198:
4174:
4146:
4119:
4084:
4057:
4030:
4003:
3976:
3949:
3936:
3902:
3883:
3856:
3829:
3802:
3775:
3762:
3749:
3722:
3695:
3668:
3641:
3613:
3586:
3559:
3546:
3518:
3491:
3478:
3465:
3452:
3425:
3398:
3371:
3344:
3311:
3298:
3283:
3266:
3247:
3234:
3207:
3180:
3153:
3140:
3127:
3096:
3083:
3058:
3022:
2994:
2981:
2968:
2941:
2914:
2887:
2860:
2833:
2806:
2779:
2751:
2724:
2705:
2682:
2649:
2622:
2595:
2568:
2541:
2528:
2515:
2488:
2461:
2438:
2411:
2398:
2385:
2357:
2330:
2303:
2275:
2214:
2187:
2160:
1879:is the 1994 total synthesis of
796: — Removed with potassium
4773:J. Chem. Soc., Perkin Trans. 1
4680:Weng C. Chan, Peter D. White:
4600:K.C. Nicolaou, E.J. Sorensen:
4184:J. Chem. Soc., Perkin Trans. 1
3240:Weng C. Chan, Peter D. White:
2691:J. Chem. Soc., Perkin Trans. 1
2316:J. Chem. Soc., Perkin Trans. 1
2132:
2119:
2106:
2087:
2060:
2053:Weng C. Chan, Peter D. White:
2047:
1991:
1966:
1354:-acetals are, unlike the pure
1040:9-Fluorenylmethyloxycarbonyl (
991:(Cbz) group — Removed by
740:metal oxidants: base-buffered
417:(from a protected alcohol) or
227:§ Industrial applications
1:
4810:A review by Prof. Kocienski.
4563:10.1016/S0040-4020(01)96007-7
4537:10.1016/S0040-4020(01)96006-5
4511:10.1016/S0040-4020(01)96005-3
2182:doi:10.1002/jlac.198619860714
1959:
1842:(Tamiflu, an antiviral drug)
1725:Photolabile protecting groups
1069:solid phase peptide synthesis
1035:solid phase peptide synthesis
166:, the amino acid is shown in
4761:doi:10.1002/ange.19961081805
4668:10.1016/0307-4412(79)90078-5
4589:doi:10.1002/hlca.19340170136
3929:10.1016/j.tetlet.2012.07.094
3608:doi:10.1002/hlca.19860690311
3581:doi:10.1002/hlca.19830660815
2082:doi:10.1002/ange.19961081805
2013:doi:10.1002/ange.19961081805
1764:
1366:-protected carbonyl groups.
973:
821:
377:. They can be removed with
7:
3295:retrieved 16 November 2013.
3261:Peptide Synthesis Protocols
1691:tetrabutylammonium fluoride
1648:Phosphate protecting groups
1233:ammonium cerium(IV) nitrate
1170:) groups — Removed by
913:and also relatively strong
866:diisobutyl aluminum hydride
763:tetrabutylammonium fluoride
736: — Removed by acid or
615:tetrabutylammonium fluoride
383:dichlorodicyanobenzoquinone
62:multistep organic synthesis
10:
4869:
3029:derivatives with the LiAlH
2447:Carbonhydr. Chem. Biochem.
1805:
1740:trimethylsilyldiazomethane
1240:Carbonyl protecting groups
366:removes a wide variety of
134:enantioselective synthesis
2662:FEMS Microbiology Letters
1946:oligonucleotide synthesis
1877:natural product synthesis
1655:oligonucleotide synthesis
1600:
1553:) — Also removed in
1231:(PMP) group – Removed by
1208:, more labile than benzyl
1109:oligonucleotide synthesis
1014:-Methoxybenzyloxycarbonyl
909:, but are a quite potent
753:oligonucleotide synthesis
708:Methoxyethoxymethyl ether
687:oligonucleotide synthesis
619:oligonucleotide synthesis
451:Alcohol protecting groups
318:-labile protecting groups
312:-labile protecting groups
306:-labile protecting groups
300:-labile protecting groups
294:-labile protecting groups
288:-labile protecting groups
182:) benzyl ester protected
77:lithium aluminium hydride
2700:doi:10.1039/P19810001796
2481:, pp. 10023–10034;
2325:doi:10.1039/P19810002055
1977:(3 ed.). J. Wiley.
1718:
1192:(Bn) group – Removed by
817:(THF) – Removed by acid.
446:Common protecting groups
126:chiral protecting groups
87:. It always reacts with
4642:doi:10.1021/ja00067a026
4553:, Volume 46, Issue 18,
4527:, Volume 46, Issue 18,
4501:, Volume 46, Issue 18,
4257:doi:10.1021/cr60245a003
4215:Oxford University Press
4101:Bull. Korean Chem. Soc.
3998:doi:10.1021/jo00926a024
3851:doi:10.1021/ja00841a058
3824:doi:10.1021/ja00235a052
3757:Katalytische Hydrierung
3744:doi:10.1021/jo00356a002
3717:doi:10.1021/ja00775a044
3636:doi:10.1021/ja00160a047
3541:doi:10.1021/ja00010a030
3513:doi:10.1021/ja00228a051
3447:doi:10.1021/jo00353a027
3393:doi:10.1246/cl.1981.375
3229:doi:10.1021/ja00029a031
3202:doi:10.1021/jo00405a045
3175:doi:10.1021/ja00213a031
3078:doi:10.1021/jo00253a020
3017:doi:10.1021/ja00297a038
2963:doi:10.1021/jo00193a051
2882:doi:10.1021/ja00325a032
2855:doi:10.1021/ja00388a074
2801:doi:10.1021/ja00474a058
2774:doi:10.1021/jo01323a017
2746:doi:10.1021/ja00242a053
2644:doi:10.1021/ja00341a055
2617:doi:10.1021/ja00379a037
2590:doi:10.1021/jo00172a070
2563:doi:10.1021/ja00547a037
2380:doi:10.1021/ja00036a045
2352:doi:10.1021/ja00241a063
2298:doi:10.1021/jo00289a004
2270:doi:10.1021/ja00168a071
2236:doi:10.1021/jo00019a004
2209:doi:10.1021/ja00175a038
2155:doi:10.1021/ja00164a023
2031:Oxford University Press
1938:Robert Bruce Merrifield
1823:Industrial applications
1755:Due to this effect the
1679:methylmagnesium bromide
1111:for protection of N in
968:catalytic hydrogenation
879:Amine protecting groups
769:) or in tetrahydrofuran
744:in wet acetonitrile or
641:(Bn) — Removed by
535:
277:Cleavage categorization
4819:Organic-Reaction.com:
4780:, pp. 4005–4037;
4759:, pp. 2192–2219;
4707:, pp. 2223–2311;
4640:, pp. 6094–6100;
4359:, pp. 4163–4166;
4309:, pp. 3475–3478;
4282:, pp. 4133–4170;
4191:, pp. 3555–3558;
4139:, pp. 1163–1190;
4112:, pp. 2757–2758;
4077:, pp. 1021–1028;
4050:, pp. 6291–6293;
3996:, pp. 1426–1427;
3969:, pp. 2035–2052;
3876:, pp. 3051–3054;
3849:, pp. 2287–2288;
3795:, pp. 3573–3576;
3715:, pp. 7132–7137;
3688:, pp. 3269–3274;
3661:, pp. 2565–2566;
3634:, pp. 1607–1617;
3579:, pp. 2501–2511;
3539:, pp. 3850–3866;
3511:, pp. 6890–6891;
3364:, pp. 1357–1358;
3200:, pp. 2285–2286;
3120:, pp. 2093–2096;
3051:, pp. 3721–3727;
3015:, pp. 3279–3285;
2961:, pp. 3671–3672;
2934:, pp. 5417–5418;
2880:, pp. 3869–3870;
2853:, pp. 6818–6820;
2826:, pp. 3269–3270;
2799:, pp. 1942–1943;
2772:, pp. 1438–1447;
2744:, pp. 2523–2525;
2698:, pp. 1796–1801;
2615:, pp. 4251–4253;
2588:, pp. 4785–4786;
2561:, pp. 7962–7965;
2525:‑methoxybenzyl.
2378:, pp. 3910–3926;
2350:, pp. 2208–2210;
2323:, pp. 2055–2058;
2268:, pp. 4991–4993;
2234:, pp. 5496–5498;
2207:, pp. 7001–7031;
2180:, pp. 1281–1308;
2153:, pp. 2998–3017;
2080:, pp. 2195–2200;
1956:
1918:
1899:
1866:potassium permanganate
1861:
1815:
1802:
1753:
1744:kinetic isotope effect
1715:
1701:
1644:
1591:organolithium reagents
1425:
1297:palladium(II) chloride
1277:
1269:
1020:, more labile than Cbz
902:
875:
861:
826:The 1,2‑diols (
748:in wet tetrahydrofuran
734:Methylthiomethyl ether
532:
506:
439:
399:
392:
379:ceric ammonium nitrate
199:
41:
4656:Biochemical Education
4169:doi:10.1021/ol0070029
4141:doi:10.1021/cr9803840
4025:doi:10.1021/jo9713363
3971:doi:10.1021/cr950083f
3338:10.1055/s-2006-951530
3227:, pp. 998–1010;
3173:, p. 1547–1557;
3076:, pp. 4274–4282
1954:
1916:
1897:
1859:
1810:
1796:
1751:
1714:
1706:dicobalt octacarbonyl
1700:Alkyne TMS protection
1699:
1643:
1632:Protection through a
1627:titanocene dichloride
1543:2,6-diisopropylphenol
1501:and methyl iodide in
1424:
1275:
1267:
1063:in DMF for sensitive
1057:-Methyl-2-pyrrolidone
886:
874:
860:
531:
511:chlorotrimethylsilane
504:
438:
398:
391:
222:solid-phase synthesis
203:Orthogonal protection
159:
152:Orthogonal protection
24:
4782:doi:10.1039/A803688H
4587:, pp. 311–328;
4193:doi:10.1039/b006759h
4167:, pp. 679–681;
4023:, pp. 169–176;
3822:, pp. 287–289;
3742:, pp. 773–784;
3606:, pp. 621–625;
3445:, pp. 404–407;
3418:, pp. 705–708;
3391:, pp. 375–376;
2907:, pp. 445–448;
2642:, pp. 625–627;
2508:, pp. 885–888;
2431:, pp. 579–580;
2296:, pp. 410–412;
1780:biomimetic synthesis
1634:Diels-Alder reaction
1429:Types of protectants
1276:1,3‑Propadiol
1214:(DMPM) – Removed by
1157:sodium naphthalenide
658:-Methoxybenzyl ether
603:in water or pyridine
4826:Universität Marburg
4741:Michael Schelhaas,
4725:Philip J. Kocieński
4467:10.1038/nature05569
4459:2007Natur.446..404B
4375:J. Organomet. Chem.
4325:J. Organomet. Chem.
4255:, pp. 73–106;
3946:, pp. 139–142.
3488:, pp. 178–180.
3308:, pp. 199–201.
3272:B. Liebe, H. Kunz:
3137:, pp. 220–227.
2721:, pp. 276–277.
2521:See literature for
1831:(sweetener) or the
1788:
1736:transesterification
1685:in tetrahydrofuran/
1218:, more labile than
1212:3,4-Dimethoxybenzyl
1204:(PMB) – Removed by
1180:tributyltin hydride
1162:Other sulfonamide (
718:Methoxymethyl ether
584:potassium carbonate
4848:Chemical synthesis
3755:F. Zymalkokowski:
3462:, S. 167–170.
2173:Liebigs Ann. Chem.
1957:
1919:
1900:
1862:
1816:
1803:
1786:
1754:
1716:
1702:
1667:. thiophenole/TEA.
1645:
1539:2,6-dimethylphenol
1495:pig liver esterase
1426:
1301:iron(III) chloride
1278:
1270:
903:
876:
862:
714:in dichloromethane
576:Potassium fluoride
533:
507:
440:
400:
393:
200:
42:
4853:Protecting groups
4768:Protecting groups
4748:Angewandte Chemie
4729:Protecting Groups
4629:J. Am. Chem. Soc.
4453:(7134): 404–408.
4422:10.1021/ol070820h
4416:(14): 2649–2651.
4352:Tetrahedron Lett.
4298:Tetrahedron Lett.
4228:978-0-19-850346-0
4209:Organic Chemistry
4098:/Ga System", in:
4039:Tetrahedron Lett.
3944:Protecting Groups
3922:(39): 5287–5289.
3916:Tetrahedron Lett.
3899:, pp. 63–64.
3865:Tetrahedron Lett.
3838:J. Am. Chem. Soc.
3811:J. Am. Chem. Soc.
3784:Tetrahedron Lett.
3770:Protecting Groups
3704:J. Am. Chem. Soc.
3650:Tetrahedron Lett.
3623:J. Am. Chem. Soc.
3554:Protecting Groups
3528:J. Am. Chem. Soc.
3500:J. Am. Chem. Soc.
3486:Protecting Groups
3473:Protecting Groups
3460:Protecting Groups
3407:Tetrahedron Lett.
3353:Tetrahedron Lett.
3332:(19): 3294–3298.
3306:Protecting Groups
3253:Gregg B. Fields:
3244:, pp. 27–30.
3216:J. Am. Chem. Soc.
3162:J. Am. Chem. Soc.
3148:Protecting Groups
3135:Protecting Groups
3109:Tetrahedron Lett.
3091:Protecting Groups
3004:J. Am. Chem. Soc.
2989:Protecting Groups
2978:, pp. 59–60.
2976:Protecting Groups
2923:Tetrahedron Lett.
2896:Tetrahedron Lett.
2869:J. Am. Chem. Soc.
2842:J. Am. Chem. Soc.
2815:Tetrahedron Lett.
2788:J. Am. Chem. Soc.
2733:J. Am. Chem. Soc.
2631:J. Am. Chem. Soc.
2604:J. Am. Chem. Soc.
2550:J. Am. Chem. Soc.
2536:Protecting Groups
2497:Tetrahedron Lett.
2420:Tetrahedron Lett.
2408:, pp. 46–49.
2406:Protecting Groups
2393:Protecting Groups
2367:J. Am. Chem. Soc.
2339:J. Am. Chem. Soc.
2257:J. Am. Chem. Soc.
2196:J. Am. Chem. Soc.
2142:J. Am. Chem. Soc.
2127:Protecting Groups
2114:Protecting Groups
2069:Angewandte Chemie
2040:978-0-19-963724-9
2011:, pp. 2194;
2000:Angewandte Chemie
1984:978-0-471-16019-9
1934:peptide synthesis
1849:(Vitamin C) à la
1820:
1819:
1687:dimethylsulfoxide
1532:carboalkoxylation
1499:caesium carbonate
1482:Protecting groups
1369:The formation of
1074:Allyloxycarbamate
1050:dimethylformamide
1027:-Butyloxycarbonyl
927:, typically as a
907:peptide synthesis
800:‑butoxide
784:Tert-butyl ethers
742:mercuric chloride
724:Tetrahydropyranyl
703:hydrochloric acid
601:hydrogen fluoride
459:, deprotected by
327:protecting groups
174:) Fmoc-protected
69:organic compounds
4860:
4821:Protecting Group
4743:Herbert Waldmann
4712:
4691:
4685:
4678:
4672:
4671:
4651:
4645:
4624:
4618:
4611:
4605:
4598:
4592:
4576:Helv. Chim. Acta
4571:
4565:
4545:
4539:
4519:
4513:
4493:
4487:
4486:
4440:
4434:
4433:
4406:
4397:
4391:
4370:
4364:
4347:
4341:
4320:
4314:
4293:
4287:
4266:
4260:
4239:
4233:
4232:
4212:
4202:
4196:
4178:
4172:
4150:
4144:
4123:
4117:
4088:
4082:
4061:
4055:
4034:
4028:
4007:
4001:
3980:
3974:
3953:
3947:
3942:P.J. Kocieński:
3940:
3934:
3933:
3931:
3906:
3900:
3887:
3881:
3860:
3854:
3833:
3827:
3806:
3800:
3779:
3773:
3768:P.J. Kocieński:
3766:
3760:
3753:
3747:
3726:
3720:
3699:
3693:
3672:
3666:
3645:
3639:
3617:
3611:
3595:Helv. Chim. Acta
3590:
3584:
3568:Helv. Chim. Acta
3563:
3557:
3552:P.J. Kocieński:
3550:
3544:
3522:
3516:
3495:
3489:
3484:P.J. Kocieński:
3482:
3476:
3471:P.J. Kocieński:
3469:
3463:
3458:P.J. Kocieński:
3456:
3450:
3429:
3423:
3402:
3396:
3375:
3369:
3348:
3342:
3341:
3315:
3309:
3304:P.J. Kocieński:
3302:
3296:
3287:
3281:
3270:
3264:
3251:
3245:
3238:
3232:
3211:
3205:
3184:
3178:
3157:
3151:
3146:P.J. Kocieński:
3144:
3138:
3133:P.J. Kocieński:
3131:
3125:
3100:
3094:
3089:P.J. Kocieński:
3087:
3081:
3062:
3056:
3026:
3020:
2998:
2992:
2987:P.J. Kocieński:
2985:
2979:
2974:P.J. Kocieński:
2972:
2966:
2945:
2939:
2918:
2912:
2891:
2885:
2864:
2858:
2837:
2831:
2810:
2804:
2783:
2777:
2755:
2749:
2728:
2722:
2709:
2703:
2686:
2680:
2679:
2677:
2668:(2–3): 225–229.
2653:
2647:
2626:
2620:
2599:
2593:
2572:
2566:
2545:
2539:
2534:P.J. Kocieński:
2532:
2526:
2519:
2513:
2492:
2486:
2465:
2459:
2442:
2436:
2415:
2409:
2404:P.J. Kocieński:
2402:
2396:
2391:P.J. Kocieński:
2389:
2383:
2361:
2355:
2334:
2328:
2307:
2301:
2279:
2273:
2248:
2239:
2218:
2212:
2191:
2185:
2169:
2164:
2158:
2136:
2130:
2125:P.J. Kocieński:
2123:
2117:
2112:P.J. Kocieński:
2110:
2104:
2103:, pp. 1–26.
2091:
2085:
2064:
2058:
2057:, S. 10–12.
2051:
2045:
2044:
2022:
2016:
1995:
1989:
1988:
1970:
1789:
1785:
1729:proof of concept
1468:carboxylic acids
1106:
1105:
1096:
1095:
1005:activated carbon
900:
852:cyclopentylidene
788:hydrogen bromide
413:. The residual
343:steric hindrance
257:
238:
165:
118:oligosaccharides
98:protecting group
58:chemoselectivity
54:functional group
50:protective group
46:protecting group
4868:
4867:
4863:
4862:
4861:
4859:
4858:
4857:
4838:
4837:
4791:
4721:
4719:Further reading
4716:
4715:
4692:
4688:
4679:
4675:
4652:
4648:
4625:
4621:
4612:
4608:
4599:
4595:
4572:
4568:
4546:
4542:
4520:
4516:
4494:
4490:
4441:
4437:
4404:
4398:
4394:
4371:
4367:
4348:
4344:
4321:
4317:
4294:
4290:
4267:
4263:
4240:
4236:
4229:
4203:
4199:
4179:
4175:
4151:
4147:
4124:
4120:
4097:
4093:
4089:
4085:
4062:
4058:
4035:
4031:
4008:
4004:
3981:
3977:
3954:
3950:
3941:
3937:
3907:
3903:
3888:
3884:
3861:
3857:
3834:
3830:
3807:
3803:
3780:
3776:
3772:, pp. 136.
3767:
3763:
3754:
3750:
3727:
3723:
3700:
3696:
3673:
3669:
3646:
3642:
3618:
3614:
3591:
3587:
3564:
3560:
3556:, pp. 119.
3551:
3547:
3523:
3519:
3496:
3492:
3483:
3479:
3475:, pp. 176.
3470:
3466:
3457:
3453:
3430:
3426:
3403:
3399:
3376:
3372:
3349:
3345:
3321:
3316:
3312:
3303:
3299:
3288:
3284:
3271:
3267:
3252:
3248:
3239:
3235:
3212:
3208:
3185:
3181:
3158:
3154:
3145:
3141:
3132:
3128:
3101:
3097:
3088:
3084:
3063:
3059:
3036:
3032:
3027:
3023:
2999:
2995:
2986:
2982:
2973:
2969:
2946:
2942:
2919:
2915:
2892:
2888:
2865:
2861:
2838:
2834:
2811:
2807:
2784:
2780:
2756:
2752:
2729:
2725:
2710:
2706:
2687:
2683:
2654:
2650:
2627:
2623:
2600:
2596:
2573:
2569:
2546:
2542:
2533:
2529:
2520:
2516:
2493:
2489:
2466:
2462:
2443:
2439:
2416:
2412:
2403:
2399:
2390:
2386:
2362:
2358:
2335:
2331:
2312:
2308:
2304:
2280:
2276:
2249:
2242:
2219:
2215:
2192:
2188:
2167:
2165:
2161:
2137:
2133:
2124:
2120:
2111:
2107:
2092:
2088:
2065:
2061:
2052:
2048:
2041:
2023:
2019:
1996:
1992:
1985:
1971:
1967:
1962:
1825:
1767:
1721:
1674:
1650:
1603:
1587:
1484:
1464:
1431:
1282:ethylene glycol
1268:Ethylene glycol
1242:
1172:samarium iodide
1146:
1142:
1103:
1102:
1093:
1092:
1032:
976:
896:
881:
848:cyclohexylidene
824:
815:Tetrahydrofuran
810:
696:Benzyloxymethyl
683:Dimethoxytrityl
634:Benzyl ethers:
597:tetrahydrofuran
538:
491:pivalate esters
478:might be used.
453:
448:
403:Allyl compounds
279:
271:hydroxyl groups
261:
258:
249:
239:
161:
154:
75:. For example,
26:Ethylene glycol
17:
12:
11:
5:
4866:
4856:
4855:
4850:
4836:
4835:
4823:
4817:
4812:
4807:
4802:
4797:
4790:
4789:External links
4787:
4786:
4785:
4764:
4739:
4732:
4720:
4717:
4714:
4713:
4686:
4673:
4646:
4619:
4606:
4593:
4566:
4540:
4514:
4488:
4435:
4392:
4365:
4342:
4315:
4288:
4261:
4234:
4227:
4197:
4173:
4145:
4118:
4095:
4091:
4083:
4056:
4029:
4002:
3975:
3948:
3935:
3901:
3882:
3855:
3828:
3801:
3774:
3761:
3748:
3721:
3694:
3667:
3640:
3612:
3585:
3558:
3545:
3517:
3490:
3477:
3464:
3451:
3424:
3397:
3370:
3343:
3319:
3310:
3297:
3289:ChemPep Inc.:
3282:
3265:
3246:
3233:
3206:
3179:
3152:
3150:, p. 195.
3139:
3126:
3095:
3093:, p. 186.
3082:
3057:
3037:reagent", in:
3034:
3030:
3021:
2993:
2980:
2967:
2940:
2913:
2886:
2859:
2832:
2805:
2778:
2750:
2723:
2704:
2681:
2648:
2621:
2594:
2567:
2540:
2527:
2514:
2487:
2460:
2458:, pp. 79.
2444:B. Helferich:
2437:
2410:
2397:
2384:
2356:
2329:
2310:
2302:
2274:
2240:
2213:
2186:
2159:
2131:
2118:
2105:
2086:
2059:
2046:
2039:
2017:
1990:
1983:
1964:
1963:
1961:
1958:
1824:
1821:
1818:
1817:
1804:
1778:. In contrast
1776:drug discovery
1772:chemical yield
1766:
1763:
1762:
1761:
1742:utilizing the
1720:
1717:
1673:
1670:
1669:
1668:
1658:
1649:
1646:
1638:
1637:
1630:
1602:
1599:
1598:
1597:
1585:
1577:
1571:
1568:organometallic
1561:
1558:
1535:
1522:
1516:
1510:
1483:
1480:
1463:
1460:
1459:
1458:
1452:
1442:
1430:
1427:
1346:and the mixed
1322:-acetals, the
1241:
1238:
1237:
1236:
1229:-Methoxyphenyl
1223:
1222:-methoxybenzyl
1216:hydrogenolysis
1209:
1206:hydrogenolysis
1202:-Methoxybenzyl
1196:
1194:hydrogenolysis
1185:Benzylamines:
1183:
1182:
1160:
1144:
1140:
1134:
1128:
1084:Other amides:
1082:
1081:
1071:
1038:
1030:
1021:
1018:hydrogenolysis
1008:
993:hydrogenolysis
989:Carbobenzyloxy
986:
975:
972:
933:carbon dioxide
880:
877:
844:isopropylidene
823:
820:
819:
818:
812:
808:
805:
791:
781:
773:Other ethers:
771:
770:
756:
749:
746:silver nitrate
731:
721:
715:
705:
699:
693:
690:
676:
675:
665:
652:
646:
643:hydrogenolysis
632:
631:
625:
622:
604:
590:
572:Trimethylsilyl
567:Silyl ethers:
565:
564:
558:
552:
537:
534:
515:Direct Process
499:
498:
465:triorganosilyl
452:
449:
447:
444:
332:
331:
328:
322:
319:
313:
307:
301:
295:
289:
278:
275:
263:
262:
259:
252:
250:
240:
233:
196:hydroxyl group
184:carboxyl group
153:
150:
15:
9:
6:
4:
3:
2:
4865:
4854:
4851:
4849:
4846:
4845:
4843:
4833:
4832:
4827:
4824:
4822:
4818:
4816:
4813:
4811:
4808:
4806:
4803:
4801:
4798:
4796:
4793:
4792:
4783:
4779:
4775:
4774:
4769:
4765:
4762:
4758:
4754:
4750:
4749:
4744:
4740:
4737:
4733:
4730:
4726:
4723:
4722:
4710:
4706:
4702:
4698:
4697:
4690:
4683:
4677:
4669:
4665:
4661:
4657:
4650:
4643:
4639:
4635:
4631:
4630:
4623:
4616:
4610:
4603:
4597:
4590:
4586:
4582:
4578:
4577:
4570:
4564:
4560:
4556:
4552:
4549:
4544:
4538:
4534:
4530:
4526:
4523:
4518:
4512:
4508:
4504:
4500:
4497:
4492:
4484:
4480:
4476:
4472:
4468:
4464:
4460:
4456:
4452:
4448:
4447:
4439:
4431:
4427:
4423:
4419:
4415:
4412:
4411:
4403:
4396:
4389:
4385:
4381:
4377:
4376:
4369:
4362:
4358:
4354:
4353:
4346:
4339:
4335:
4331:
4327:
4326:
4319:
4312:
4308:
4304:
4300:
4299:
4292:
4285:
4281:
4277:
4273:
4272:
4265:
4258:
4254:
4250:
4246:
4245:
4238:
4230:
4224:
4220:
4216:
4211:
4210:
4201:
4194:
4190:
4186:
4185:
4177:
4170:
4166:
4162:
4158:
4157:
4149:
4142:
4138:
4134:
4130:
4129:
4122:
4115:
4111:
4107:
4103:
4102:
4087:
4080:
4076:
4072:
4068:
4067:
4060:
4053:
4049:
4045:
4041:
4040:
4033:
4026:
4022:
4018:
4014:
4013:
4012:J. Org. Chem.
4006:
3999:
3995:
3991:
3987:
3986:
3985:J. Org. Chem.
3979:
3972:
3968:
3964:
3960:
3959:
3952:
3945:
3939:
3930:
3925:
3921:
3918:
3917:
3912:
3905:
3898:
3894:
3893:
3886:
3879:
3875:
3871:
3867:
3866:
3859:
3852:
3848:
3844:
3840:
3839:
3832:
3825:
3821:
3817:
3813:
3812:
3805:
3798:
3794:
3790:
3786:
3785:
3778:
3771:
3765:
3758:
3752:
3745:
3741:
3737:
3733:
3732:
3731:J. Org. Chem.
3725:
3718:
3714:
3710:
3706:
3705:
3698:
3691:
3687:
3683:
3679:
3678:
3671:
3664:
3660:
3656:
3652:
3651:
3644:
3637:
3633:
3629:
3625:
3624:
3616:
3609:
3605:
3601:
3597:
3596:
3589:
3582:
3578:
3574:
3570:
3569:
3562:
3555:
3549:
3542:
3538:
3534:
3530:
3529:
3521:
3514:
3510:
3506:
3502:
3501:
3494:
3487:
3481:
3474:
3468:
3461:
3455:
3448:
3444:
3440:
3436:
3435:
3434:J. Org. Chem.
3428:
3421:
3417:
3413:
3409:
3408:
3401:
3394:
3390:
3386:
3382:
3381:
3374:
3367:
3363:
3359:
3355:
3354:
3347:
3339:
3335:
3331:
3327:
3326:
3314:
3307:
3301:
3294:
3293:
3286:
3279:
3275:
3269:
3262:
3258:
3257:
3250:
3243:
3237:
3230:
3226:
3222:
3218:
3217:
3210:
3203:
3199:
3195:
3191:
3190:
3189:J. Org. Chem.
3183:
3176:
3172:
3168:
3164:
3163:
3156:
3149:
3143:
3136:
3130:
3123:
3119:
3115:
3111:
3110:
3105:
3099:
3092:
3086:
3079:
3075:
3071:
3067:
3066:J. Org. Chem.
3061:
3054:
3050:
3046:
3042:
3041:
3025:
3018:
3014:
3010:
3006:
3005:
2997:
2991:, p. 62.
2990:
2984:
2977:
2971:
2964:
2960:
2956:
2952:
2951:
2950:J. Org. Chem.
2944:
2937:
2933:
2929:
2925:
2924:
2917:
2910:
2906:
2902:
2898:
2897:
2890:
2883:
2879:
2875:
2871:
2870:
2863:
2856:
2852:
2848:
2844:
2843:
2836:
2829:
2825:
2821:
2817:
2816:
2809:
2802:
2798:
2794:
2790:
2789:
2782:
2775:
2771:
2767:
2763:
2762:
2761:J. Org. Chem.
2754:
2747:
2743:
2739:
2735:
2734:
2727:
2720:
2716:
2715:
2708:
2701:
2697:
2693:
2692:
2685:
2676:
2671:
2667:
2663:
2659:
2652:
2645:
2641:
2637:
2633:
2632:
2625:
2618:
2614:
2610:
2606:
2605:
2598:
2591:
2587:
2583:
2579:
2578:
2577:J. Org. Chem.
2571:
2564:
2560:
2556:
2552:
2551:
2544:
2538:, p. 77.
2537:
2531:
2524:
2518:
2511:
2507:
2503:
2499:
2498:
2491:
2484:
2480:
2476:
2472:
2471:
2464:
2457:
2453:
2449:
2448:
2441:
2434:
2430:
2426:
2422:
2421:
2414:
2407:
2401:
2395:, p. 40.
2394:
2388:
2381:
2377:
2373:
2369:
2368:
2360:
2353:
2349:
2345:
2341:
2340:
2333:
2326:
2322:
2318:
2317:
2306:
2299:
2295:
2291:
2287:
2286:
2285:J. Org. Chem.
2278:
2271:
2267:
2263:
2259:
2258:
2253:
2247:
2245:
2237:
2233:
2229:
2225:
2224:
2223:J. Org. Chem.
2217:
2210:
2206:
2202:
2198:
2197:
2190:
2183:
2179:
2175:
2174:
2163:
2156:
2152:
2148:
2144:
2143:
2135:
2129:, p. 31.
2128:
2122:
2116:, p. 29.
2115:
2109:
2102:
2098:
2097:
2090:
2083:
2079:
2075:
2071:
2070:
2063:
2056:
2050:
2042:
2036:
2032:
2028:
2021:
2014:
2010:
2006:
2002:
2001:
1994:
1986:
1980:
1976:
1969:
1965:
1953:
1949:
1947:
1943:
1939:
1935:
1930:
1928:
1924:
1915:
1911:
1909:
1905:
1896:
1892:
1890:
1886:
1885:Yoshito Kishi
1882:
1878:
1873:
1871:
1867:
1858:
1854:
1852:
1848:
1847:ascorbic acid
1843:
1841:
1837:
1834:
1830:
1813:
1809:
1800:
1795:
1791:
1790:
1784:
1781:
1777:
1773:
1758:
1757:quantum yield
1750:
1745:
1741:
1737:
1734:
1733:photochemical
1730:
1726:
1723:
1722:
1713:
1709:
1707:
1698:
1694:
1692:
1688:
1684:
1680:
1666:
1662:
1659:
1656:
1652:
1651:
1642:
1635:
1631:
1628:
1624:
1620:
1616:
1615:
1614:
1612:
1611:isomerization
1608:
1607:electrophilic
1596:
1592:
1588:
1581:
1578:
1575:
1572:
1569:
1565:
1562:
1559:
1556:
1552:
1550:
1544:
1540:
1536:
1533:
1529:
1527:
1523:
1520:
1517:
1514:
1511:
1508:
1504:
1500:
1496:
1492:
1489:
1486:
1485:
1479:
1475:
1473:
1469:
1456:
1453:
1450:
1447:– Removed by
1446:
1443:
1440:
1436:
1433:
1432:
1423:
1419:
1417:
1412:
1410:
1406:
1402:
1398:
1394:
1392:
1388:
1384:
1380:
1376:
1372:
1367:
1365:
1361:
1357:
1353:
1349:
1345:
1341:
1337:
1333:
1329:
1325:
1321:
1317:
1312:
1308:
1306:
1302:
1298:
1294:
1289:
1287:
1286:1,3-propadiol
1283:
1274:
1266:
1262:
1260:
1256:
1252:
1248:
1234:
1230:
1228:
1224:
1221:
1217:
1213:
1210:
1207:
1203:
1201:
1197:
1195:
1191:
1188:
1187:
1186:
1181:
1177:
1173:
1169:
1165:
1161:
1158:
1154:
1150:
1138:
1135:
1132:
1129:
1126:
1122:
1118:
1114:
1110:
1100:
1090:
1087:
1086:
1085:
1079:
1075:
1072:
1070:
1067:. Common in
1066:
1065:glycopeptides
1062:
1058:
1056:
1051:
1047:
1043:
1039:
1036:
1028:
1026:
1022:
1019:
1015:
1013:
1009:
1006:
1002:
998:
994:
990:
987:
984:
981:
980:
979:
971:
969:
965:
961:
957:
953:
949:
945:
940:
938:
934:
930:
926:
922:
918:
916:
912:
908:
899:
894:
890:
885:
873:
869:
867:
859:
855:
853:
849:
845:
841:
837:
833:
829:
816:
813:
806:
803:
799:
795:
792:
789:
785:
782:
779:
776:
775:
774:
768:
764:
760:
757:
754:
750:
747:
743:
739:
735:
732:
729:
725:
722:
719:
716:
713:
709:
706:
704:
700:
697:
694:
691:
688:
684:
681:
680:
679:
673:
669:
666:
663:
659:
657:
653:
650:
647:
644:
640:
637:
636:
635:
629:
626:
623:
620:
616:
612:
608:
605:
602:
598:
594:
593:Triethylsilyl
591:
589:
585:
581:
577:
574:(TMS) —
573:
570:
569:
568:
562:
559:
556:
553:
550:
549:Acetoxy group
546:
543:
542:
541:
530:
526:
522:
520:
516:
512:
503:
496:
495:
494:
492:
488:
484:
479:
477:
473:
472:(hemi)acetals
469:
466:
462:
458:
443:
437:
433:
431:
427:
422:
420:
416:
412:
408:
404:
397:
390:
386:
384:
380:
376:
371:
369:
368:benzyl groups
365:
364:hydrogenation
360:
358:
354:
353:biological pH
350:
346:
344:
340:
335:
329:
326:
323:
320:
317:
314:
311:
308:
305:
302:
299:
296:
293:
290:
287:
284:
283:
282:
274:
272:
268:
256:
251:
248:
244:
237:
232:
231:
230:
228:
223:
218:
216:
212:
208:
204:
197:
193:
189:
185:
181:
177:
173:
169:
164:
158:
149:
145:
143:
139:
138:shikimic acid
135:
131:
127:
123:
119:
115:
111:
105:
103:
99:
95:
90:
86:
82:
78:
74:
70:
65:
63:
59:
55:
51:
47:
39:
35:
31:
27:
23:
19:
4830:
4777:
4771:
4763:(in German).
4756:
4752:
4746:
4735:
4728:
4704:
4700:
4694:
4689:
4681:
4676:
4662:(4): 93–94.
4659:
4655:
4649:
4637:
4633:
4627:
4622:
4614:
4609:
4601:
4596:
4584:
4580:
4574:
4569:
4554:
4547:
4543:
4528:
4521:
4517:
4502:
4495:
4491:
4450:
4444:
4438:
4413:
4408:
4395:
4383:
4379:
4373:
4368:
4356:
4350:
4345:
4333:
4329:
4323:
4318:
4306:
4302:
4296:
4291:
4279:
4275:
4269:
4264:
4252:
4248:
4242:
4237:
4208:
4200:
4188:
4182:
4176:
4164:
4160:
4154:
4148:
4136:
4132:
4126:
4121:
4109:
4105:
4099:
4086:
4074:
4070:
4064:
4059:
4047:
4043:
4037:
4032:
4020:
4016:
4010:
4005:
3993:
3989:
3983:
3978:
3966:
3962:
3956:
3951:
3943:
3938:
3919:
3914:
3904:
3896:
3890:
3885:
3873:
3869:
3863:
3858:
3846:
3842:
3836:
3831:
3819:
3815:
3809:
3804:
3799:(in German).
3792:
3788:
3782:
3777:
3769:
3764:
3756:
3751:
3739:
3735:
3729:
3724:
3712:
3708:
3702:
3697:
3685:
3681:
3675:
3670:
3658:
3654:
3648:
3643:
3631:
3627:
3621:
3615:
3603:
3599:
3593:
3588:
3576:
3572:
3566:
3561:
3553:
3548:
3536:
3532:
3526:
3520:
3508:
3504:
3498:
3493:
3485:
3480:
3472:
3467:
3459:
3454:
3442:
3438:
3432:
3427:
3415:
3411:
3405:
3400:
3388:
3384:
3378:
3373:
3361:
3357:
3351:
3346:
3329:
3323:
3313:
3305:
3300:
3291:
3285:
3278:Angew. Chem.
3277:
3273:
3268:
3260:
3255:
3249:
3241:
3236:
3224:
3220:
3214:
3209:
3197:
3193:
3187:
3182:
3170:
3166:
3160:
3155:
3147:
3142:
3134:
3129:
3117:
3113:
3107:
3103:
3098:
3090:
3085:
3073:
3069:
3065:
3060:
3048:
3044:
3038:
3024:
3012:
3008:
3002:
2996:
2988:
2983:
2975:
2970:
2958:
2954:
2948:
2943:
2931:
2927:
2921:
2916:
2904:
2900:
2894:
2889:
2877:
2873:
2867:
2862:
2850:
2846:
2840:
2835:
2823:
2819:
2813:
2808:
2796:
2792:
2786:
2781:
2769:
2765:
2759:
2753:
2741:
2737:
2731:
2726:
2718:
2712:
2707:
2695:
2689:
2684:
2665:
2661:
2651:
2639:
2635:
2629:
2624:
2612:
2608:
2602:
2597:
2585:
2581:
2575:
2570:
2558:
2554:
2548:
2543:
2535:
2530:
2522:
2517:
2505:
2501:
2495:
2490:
2478:
2474:
2468:
2463:
2455:
2451:
2445:
2440:
2428:
2424:
2418:
2413:
2405:
2400:
2392:
2387:
2375:
2371:
2365:
2359:
2347:
2343:
2337:
2332:
2320:
2314:
2305:
2293:
2289:
2283:
2277:
2265:
2261:
2255:
2231:
2227:
2221:
2216:
2204:
2200:
2194:
2189:
2177:
2171:
2162:
2150:
2146:
2140:
2134:
2126:
2121:
2113:
2108:
2100:
2094:
2089:
2084:(in German).
2077:
2073:
2067:
2062:
2054:
2049:
2026:
2020:
2015:(in German).
2008:
2004:
1998:
1993:
1974:
1968:
1941:
1931:
1920:
1901:
1888:
1874:
1863:
1844:
1826:
1768:
1703:
1683:butyllithium
1675:
1664:
1618:
1604:
1551:-butylphenol
1548:
1525:
1506:
1502:
1476:
1465:
1413:
1408:
1404:
1400:
1396:
1395:
1390:
1386:
1382:
1378:
1374:
1370:
1368:
1359:
1355:
1351:
1347:
1335:
1331:
1327:
1323:
1319:
1315:
1314:Besides the
1313:
1309:
1290:
1279:
1258:
1254:
1250:
1246:
1243:
1226:
1219:
1199:
1184:
1083:
1054:
1024:
1011:
978:Carbamates:
977:
963:
959:
944:phthalimides
941:
936:
921:Amine groups
919:
904:
897:
892:
863:
825:
797:
777:
772:
727:
712:zinc bromide
677:
671:
667:
655:
633:
627:
611:acetonitrile
606:
566:
539:
523:
513:(TMS-Cl), a
508:
480:
461:nucleophiles
454:
441:
429:
423:
411:noble metals
401:
375:quinomethide
372:
361:
357:temperatures
347:
336:
333:
280:
267:carbohydrate
264:
246:
242:
219:
214:
210:
202:
201:
198:of Tyrosine.
191:
187:
179:
171:
167:
162:
146:
129:
110:biomolecules
106:
102:deprotection
101:
97:
72:
66:
49:
45:
43:
36:) during an
18:
4834:(in German)
4696:Tetrahedron
4551:Tetrahedron
4525:Tetrahedron
4499:Tetrahedron
4386:, C21–C24;
4336:, C45–C48;
4271:Tetrahedron
4217:. pp.
4066:Tetrahedron
3677:Tetrahedron
3380:Chem. Lett.
3040:Tetrahedron
2470:Tetrahedron
2252:latrunculin
1908:Danishefsky
1904:Mitomycin C
1840:oseltamivir
1574:Orthoesters
1449:Lewis acids
1344:Thioacetals
1125:methylamine
911:nucleophile
840:benzylidene
580:acetic acid
426:chromophore
325:Photolabile
176:amino group
142:oseltamivir
122:nucleotides
28:protects a
4842:Categories
4410:Org. Lett.
4244:Chem. Rev.
4156:Org. Lett.
4128:Chem. Rev.
3958:Chem. Rev.
1960:References
1851:Reichstein
1812:Phil Baran
1519:Benzhydryl
1472:oxazolines
1416:hemiaminal
1305:silica gel
1176:thiophenol
1151:in liquid
1061:morpholine
1046:piperidine
956:imidazoles
519:silica gel
415:enol ether
362:Catalytic
355:(5-9) and
128:may often
56:to obtain
3892:Synthesis
2714:Synthesis
2096:Synthesis
1898:Palytoxin
1881:palytoxin
1836:synthesis
1829:sucralose
1765:Criticism
1580:Oxazoline
1570:reagents.
1455:Dithianes
1261:-acetals.
1115:and N in
1059:, or 50%
1052:(DMF) or
1001:palladium
983:Carbamate
974:Selection
929:carbamate
925:acylation
854:acetals.
822:1,2-Diols
765:in HMPT (
678:Acetals:
407:isomerize
381:(CAN) or
316:Oxidation
310:Reduction
73:protected
4475:17377577
4430:17555322
2254:A", in:
1927:aldehyde
1883:acid by
1625:or with
1609:attack,
1113:cytosine
997:hydrogen
952:pyrroles
588:methanol
561:Pivaloyl
540:Esters:
487:benzoate
298:Fluoride
207:tyrosine
114:peptides
89:carbonyl
85:alcohols
4770:", in:
4483:4357378
4455:Bibcode
3325:Synlett
1923:epoxide
1870:acetone
1547:2,6-di-
1445:Acylals
1435:Acetals
1293:Acetone
1153:ammonia
1121:ammonia
1117:adenine
1099:Benzoyl
948:Indoles
889:glycine
828:glycols
555:Benzoyl
483:acetate
419:enamine
385:(DDQ).
349:Lipases
339:silicon
130:shorten
32:(as an
4481:
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4446:Nature
4428:
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3106:, in:
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1925:to an
1661:Methyl
1601:Alkene
1528:-Butyl
1513:Benzyl
1491:esters
1488:Methyl
1439:Ketals
1364:sulfur
1340:Thiols
1330:- and
1190:Benzyl
1166:&
1149:sodium
1089:Acetyl
1078:nickel
891:. The
836:acetal
832:sugars
811:in DCM
649:Trityl
639:Benzyl
545:Acetyl
489:, and
468:ethers
457:esters
304:Enzyme
136:(e.g.
94:acetal
81:esters
34:acetal
30:ketone
4479:S2CID
4405:(PDF)
3033:-AlCl
1833:Roche
1799:Tosyl
1727:As a
1719:Other
1619:trans
1584:LiAlH
1564:Silyl
1253:– or
1235:(CAN)
1164:Nosyl
1137:Tosyl
915:bases
802:DABCO
794:Allyl
476:ether
405:will
229:).
186:and (
168:black
112:like
38:ester
4778:1998
4753:1996
4701:1992
4634:1993
4581:1934
4555:1990
4529:1990
4503:1990
4471:PMID
4426:PMID
4380:1972
4357:1977
4330:1977
4303:1971
4276:2002
4249:1967
4223:ISBN
4219:1291
4189:2000
4161:2001
4133:1999
4106:2010
4094:TiCl
4071:1998
4044:1990
4017:1998
3990:1974
3963:1996
3897:1978
3870:1978
3843:1975
3816:1987
3789:1983
3736:1986
3709:1972
3682:1978
3655:1992
3628:1990
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3505:1988
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3385:1981
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3276:In:
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3194:1978
3167:1988
3114:1984
3070:1988
3045:1982
3009:1985
2955:1984
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2847:1982
2820:1975
2793:1978
2766:1979
2738:1987
2719:1975
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2609:1982
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2425:1986
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2321:1981
2290:1990
2262:1990
2228:1991
2201:1990
2178:1986
2147:1990
2101:1980
2074:1996
2035:ISBN
2005:1996
1979:ISBN
1942:tert
1623:zinc
1549:tert
1526:tert
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1080:(0).
1042:Fmoc
1025:tert
999:and
954:und
937:tert
898:blue
893:tert
887:BOC
846:and
798:tert
738:soft
628:tert
607:tert
536:List
292:Base
286:Acid
245:and
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192:tert
170:). (
163:blue
140:for
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1936:by
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