- The Total Synthesis of Epothilone D as a Yardstick for Probing New Methodologies
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Here, a concise and highly convergent synthesis of epothilone D was investigated, relying on fragments of equal complexity that could be prepared in gram scale quantities. The strategy to construct the fragments includes the use of a previously reported enantiospecific zinc-catalyzed cross-coupling of an α-hydroxy ester triflate with a Grignard reagent, the application of a hydroboration/boron–magnesium exchange sequence for the rapid construction of the Z-substituted trisubstituted double bond present in the natural product, and a Noyori-type hydrogenation to install the β-hydroxy ester moiety of the southern part. The key to success is the diastereoselective head-to-tail macrolactonization by an intramolecular addition of the corresponding ω-alkynyl-substituted carboxylic acids to construct a new stereocenter in the macrocyclic core structure in one single step.
- Haydl, Alexander M.,Breit, Bernhard
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- PROCESS FOR MAKING CGRP RECEPTOR ANTAGONIST
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The invention encompasses a novel process for making 2-[(8R)-8-(3,5-Difluorophenyl)-10-oxo-6,9-diazaspiro[4.5]dec-9-yl]-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide, which is a CGRP receptor antagonist useful for the treatment of migraine, using an asymmetric phase-transfer catalysis route. The invention also encompasses an efficient and practical synthesis of the (R)-acid intermediate, and generates the benzylic stereocenter in an enantioselective manner.
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Page/Page column 67
(2011/02/24)
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- On the mechanism of an asymmetric α,β-unsaturated carboxylic acid hydrogenation: Application to the synthesis of a PGD2 receptor antagonist
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Ruthenium complexes employing axially chiral ligands were found to be effective asymmetric hydrogenation catalysts for the reduction of α,β-unsaturated ene acid 1-E to give 2, a prostaglandin D2 (PGD2) receptor antagonist. With [(S-B
- Tellers, David M.,McWilliams, J. Christopher,Humphrey, Guy,Journet, Michel,DiMichele, Lisa,Hinksmon, Joseph,McKeown, Arlene E.,Rosner, Thorsten,Sun, Yongkui,Tillyer, Richard D.
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p. 17063 - 17073
(2007/10/03)
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- Asymmetric hydrogenation process
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The present invention provides an asymmetric hydrogenation process for the preparation of chiral cycloalkanoindole DP receptor antagonists in high enantiomeric excess.
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Page/Page column 8-9
(2008/06/13)
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- Synthesis of New Cationic BINAP-Ruthenium(II) Complexes and their Use in Asymmetric Hydrogenation
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Reaction of 2 (1) and (S)-BINAP gives cationic BINAP-ruthenium complexes of the formula Y (2) (X = Cl, Br, and I; Y = Cl, Br, I, BF4, and BPh4; arene = C6H6 and p-MeC6H4CHMe2) which are efficient catalyst precursors for enantioselective hydrogenation of various prochiral alkenic and ketonic substrates ; a crystal structure of (2) (with X = Cl, Y = BF4) was obtained.
- Mashima, Kazushi,Kusano, Koh-hei,Ohta, Tetsuo,Noyori, Ryoji,Takaya, Hidemasa
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p. 1208 - 1210
(2007/10/02)
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