- Selective Protection of Secondary Alcohols by Using Formic Acid as a Mild and Efficient Deprotection Reagent for Primary tert -Butyldimethylsilyl Ethers
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A mild, efficient, and environmentally friendly method for the selective protection of secondary hydroxyl groups is described. The method involves the protection of both primary and secondary hydroxyl groups as tert -butyldimethylsilyl (TBDMS) ethers and selective deprotection of the primary TBDMS group with formic acid in acetonitrile/water. The rates of desilylation of primary and secondary TBDMS ethers by different concentrations of formic acid are determined. Formic acid of 5-20% concentration is found to selectively deprotect primary TBDMS ethers while keeping more than 95% of their secondary counterparts intact.
- Sapkota, Krishna,Huang, Faqing
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- Concise synthesis of the neo-clerodane skeleton of teucrolivin A using a pericyclic reaction cascade
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Herein, we describe the synthesis of advanced intermediate 39 on the path towards the total synthesis of teucrolivin A (3) in 16 steps from commercially available 1,3-cyclohexadiene. We have constructed the trans-decalin core of the natural product 3 as a
- Arns, Steve,Barriault, Louis
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- A Unified Strategy for the Asymmetric Synthesis of Highly Substituted 1,2-Amino Alcohols Leading to Highly Substituted Bisoxazoline Ligands
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A general procedure for the asymmetric synthesis of highly substituted 1,2-amino alcohols in high yield and diastereoselectivity is described that uses organometallic additions of a wide range of nucleophiles to tert-butylsulfinimines as the key step. The addition of organolithium reagents to these imines follows a modified Davis model. The diastereoselectivity for this reaction depends significantly on both the nucleophile and electrophile. These highly substituted 1,2-amino alcohols are used to synthesize stereochemically diverse and structurally novel, polysubstituted 2,2′-methylene(bisoxazoline) ligands in high yields.
- Shrestha, Bijay,Rose, Brennan T.,Olen, Casey L.,Roth, Aaron,Kwong, Adon C.,Wang, Yang,Denmark, Scott E.
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p. 3490 - 3534
(2021/02/16)
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- SYNTHESIS OF TELAPREVIR AND BOCEPREVIR, OR PHARMACEUTICALLY ACCEPTABLE SALTS OR SOLVATES AS WELL AS INTERMEDIATE PRODUCTS THEREOF INCLUDING ?-AMINO ACIDS PREPARED VIA MUKAIYAMA ALDOL ADDITION
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The invention relates to synthetic routes for preparing telaprevir and boceprevir, and its intermediates as well as peptides other than telaprevir. The synthetic routes are based on a Mukaiyama aldol addition reaction of a silyl enol ether or an enolate with an imine. The invention also refers to novel intermediates for preparing telaprevir/boceprevir or other peptides.
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Page/Page column 32
(2014/01/09)
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- Lewis base activation of Lewis acids: Catalytic, enantioselective addition of glycolate-derived silyl ketene acetals to aldehydes
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(Chemical Equation Presented) A catalytic system involving silicon tetrachloride and a chiral, Lewis basic bisphosphoramide catalyst is effective for the addition of glycolate-derived silyl ketene acetals to aldehydes. It was found that the sense of diast
- Denmark, Scott E.,Chung, Won-Jin
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p. 4582 - 4595
(2008/09/21)
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- Asymmetric total synthesis of Taxol
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The asymmetric total synthesis of Taxol was achieved by way of B to BC to ABC to ABCD ring construction. Optically active 8-membered ring enones 1 and 2 corresponding to the B ring of Taxol have been synthesized in high yields from the linear precursors 28 and 32, respectively, by intramolecular aldol cyclization using SmI2. The optically active linear polyoxy compounds 28 and 32 were obtained by way of diastereoselective aldol reaction between aldehyde 4 and ketene silyl acetal 8 catalyzed by MgBr2 · OEt2. The chiral pentanal 4 was synthesized either by asymmetric aldol reaction of achiral aldehyde 7 and ketene silyl acetal 8 by means of a chiral Lewis acid or by diastereoselective aldol reaction between the chiral aldehyde 16, derived from L-serine, and the lithium enolate derived from methyl isobutyrate. Optically active bicyclo[6.4.0]dodecanone 38β, corresponding to the BC ring system of Taxol, was prepared from 8-membered ring enone 2 in high yield by stereoselective Michael addition and successive intramolecular aldol cyclization. Furthermore, baccatin III, the ABCD ring system of Taxol, was efficiently synthesized from the BC ring system 38β by successive construction of the A and D rings by intramolecular pinacol coupling cyclization, introduction of the C-13 hydroxyl group and an oxetane-forming reaction. Finally, the total synthesis of Taxol was accomplished by dehydration condensation between a protected N-benzoylphenylisoserine 70 or 75 and 7-TES baccatin III, prepared from baccatin III. Taxol side chains 70, 73, 75, and 77, optically active protected N-benzoylphenylisoserines, were synthesized by enantioselective aldol reaction from two achiral starting materials, benzaldehyde and an enol silyl ether 65 derived from S-ethyl benzyloxyethanethioate.
- Mukaiyama, Teruaki,Shiina, Isamu,Iwadare, Hayato,Saitoh, Masahiro,Nishimura, Toshihiro,Ohkawa, Naoto,Sakoh, Hiroki,Nishimura, Koji,Tani, Yu-Ichirou,Hasegawa, Masatoshi,Yamada, Koji,Saitoh, Katsuyuki
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p. 121 - 161
(2007/10/03)
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- Method for the preparation of taxol and its derivatives
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A process of making taxane derivatives by reacting Baccatin III derivatives with an oxazolidine which contains a thioester substituent at the 4-position.
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- Highly enantio- and diastereoselective boron aldol reactions of α-heterosubstituted thioacetates with aldehydes and silyl imines
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Boron enolates derived from α-heterosubstituted thioacetates and bearing menthone-derived chiral ligands react with aldehydes to give anti aldols with excellent diastero- and enantiocontrol. Boron enolates derived from tert-butyl α-halothioacetate and bearing menthone-derived chiral ligands react with imines with excellent diastero- and enantiocontrol to give syn α-halo-β-aminothioesters, which can be converted to the corresponding aziridines by simple ring closure during LAH reduction. A key precursor of antibiotics (+)-thiamphenicol and (-)-florfenicol was synthesized.
- Gennari, Cesare,Vulpetti, Anna,Pain, Gilles
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p. 5909 - 5924
(2007/10/03)
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- Taxol semisynthesis: A highly enantio- and diastereoselective synthesis of the side chain and a new method for ester formation at C-13 using thioesters
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A very simple, new, and straightforward approach to the Paclitaxel (Taxol) and Docetaxel (Taxotere) side chains has been developed using the imine addition reaction of thioester-derived boron enolates bearing chiral ligands. The addition reaction was studied extensively, using a combination of different thioesters (ROCH2COSPh, ROCH2COSt-Bu), oxygen protecting groups (R = Bn, TBDMS, COPh, EE, TMS), chiral boron ligands [derived from both (-) and (+)-menthone], imines (PhCH=NSiMe3, PhCH=NCOPh), and in the presence or in the absence of additional Lewis acids (BF3-OEt2, Et2AlCl, TiCl4). The side chain was assembled in a few steps with the correct relative (syn) and absolute stereochemistry (2R,3S). The stereochemical outcome of the boron-mediated reaction was rationalized using chair vs boat transition state structures. A new direct route for attachment of the side chains to the baccatin nucleus using thioester chemistry has also been developed. By treatment of a mixture of a thioester (8, 12, or 17) and protected baccatin III (2b, 2c) with LHMDS, the 13-0 acylated compounds were obtained in high yield (up to 90%). Hydrolysis of 18b gave Paclitaxel (1a) in 80% yield.
- Gennari, Cesare,Carcano, Michela,Donghi, Monica,Mongelli, Nicola,Vanotti, Ermes,Vulpetti, Anna
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p. 4746 - 4755
(2007/10/03)
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- Semisynthese von Taxol: eine hochenantio- und -diastereoselektive Synthese der Seitenkette und eine neue Methode zur Esterbildung an C13 unter Verwendung von Thioestern
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Keywords: Asymmetrische Synthesen; Enolate; Imine; Taxol; Thioester
- Gennari, Cesare,Vulpetti, Anna,Donghi, Monica,Mongelli, Nicola,Vanotti, Ermes
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p. 1809 - 1812
(2007/10/03)
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