- Enantioselective Synthesis of ((1 R,2 R)-Cyclohexane-1,2-diyl)bis(methylene)dimethanesulfonate, a Lurasidone Hydrochloride Intermediate
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A concise, economical, and highly enantioselective synthesis of bismesylate intermediate of lurasidone HCl, an antipsychotic, has been developed. The key steps involved in the synthesis are thionyl chloride-catalyzed esterification of tetrahydrophthalic anhydride in MeOH, epimerization of cis to trans isomer, hydrolysis of the diester, resolution of the diacid, reduction with Red-Al, and finally bismesylation of the corresponding diol, which provided the desired intermediate ((1 R,2 R)-cyclohexane-1,2-diyl)bis(methylene) dimethanesulfonate in overall good yield.
- Ravi Ganesh,Pachore, Sharad S.,Pratap,Umesh,Basaveswara Rao,Murthy,Suresh Babu
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supporting information
p. 2676 - 2682
(2015/12/18)
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- Lipophilic oligopeptides for chemo- and enantioselective acyl transfer reactions onto alcohols
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Inspired by the extraordinary selectivities of acylases, we envisioned the use of lipophilic oligopeptidic organocatalysts for the acylative kinetic resolution/desymmetrization of rac- and meso-cycloalkane-1,2-diols. Here we describe in a full account the discovery and development process from the theoretical concept to the final catalyst, including scope and limitations. Competition experiments with various alcohols and electrophiles show the full potential of the employed oligopeptides. Additionally, we utilized NMR and IR-spectroscopic methods as well as computations to shed light on the factors responsible for the selectivity. The catalyst system can be readily modified to a multicatalyst by adding other catalytically active amino acids to the peptide backbone, enabling the stereoselective one-pot synthesis of complex molecules from simple starting materials.
- Mueller, Christian E.,Zell, Daniela,Hrdina, Radim,Wende, Raffael C.,Wanka, Lukas,Schuler, Soeren M. M.,Schreiner, Peter R.
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p. 8465 - 8484
(2013/09/24)
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- Rational tuning chelate size of bis-oxazoline ligands to improve enantioselectivity in the asymmetric aziridination of chalcones
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Chalcones were asymmetrically aziridinated with [N-(p-toluenesulfonyl) imino]phenyliodinane (PhI=NTs) as a nitrene source under catalysis of CuOTf and a series of cyclohexane-linked bis-oxazolines (cHBOXes), which are chelate size rationally tuned bis-oxazolines. The results indicate that highly enantioselective aziridination of chalcones with up to >99% ee have been achieved under catalysis of (S,S)-1,2-bis[(S)-(4-phenyl)oxazolin-2-yl] cyclohexane, which is the most-matched stereoisomer among cyclohexane-linked bis-oxazolines. It was also found that the enantioselectivity is not substituent-dependent with respect to chalcones in the present case, unlike with 1,8-anthracene-linked bis-oxazolines (AnBOXes).
- Ma, Linge,Du, Da-Ming,Xu, Jiaxi
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p. 10155 - 10158
(2007/10/03)
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- Enantiomerically pure β-amino acids: A convenient access to both enantiomers of trans-2-aminocyclohexanecarboxylic acid
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Enantiomerically pure trans-2-aminocyclohexanecarboxylic acid is an important building block for helical β-peptides. We report here that this amino acid can be obtained from trans-cyclohexane-1,2-dicarboxylic acid in good yield by a simple one-pot procedure comprising cyclization to the anhydride, amide formation with ammonia, and a subsequent Hofmann-type degradation with phenyliodine(III) bis(trifluoroacetate) (PIFA) as the oxidant. The N-Fmoc- and N-BOC-protected derivatives were obtained by treatment of the amino acid with Fmoc-OSu and BOC2O, respectively. The N-BOC derivative could be prepared in even better overall yield by a one-pot procedure leading directly from trans-cyclohexane-1,2-dicarboxylic acid to the N-BOC-protected amino acid. Both enantiomers of the starting trans-1,2-cyclohexanedicarboxylic acid can be obtained easily and in large quantities by separating commercially available racemic trans-1,2-cyclohexanedicarboxylic acid using either (R)- or (S)-1-phenethylamine. X-ray crystallography of the diastereomerically pure salt obtained from (R)-1-phenethylamine revealed that the configuration of the diacid component is (1R,2R), and not (1S,2S) as reported in the literature. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.
- Berkessel, Albrecht,Glaubitz, Katja,Lex, Johann
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p. 2948 - 2952
(2007/10/03)
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- Synthesis of new C2-symmetrical diphosphines using chiral zinc organometallics
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The new C2-symmetrical diphosphines 1-4 of potential interest for asymmetric catalysis were prepared in protected form by a convergent synthesis based on the use of readily available (S,S)-1,2-cyclohexanedicarboxylic acid 8 and the phosphorus reagent (Et2N)2PLi·BH3.
- Longeau, Alexia,Durand, Sandrine,Spiegel, Anja,Knoechel, Paul
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p. 987 - 990
(2007/10/03)
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- CARBOXY AND SUBSTITUTED CARBOXY ALKANOYL AND CYCLOALKANOYL PEPTIDES
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Peptides of the formula STR1 wherein X is various amino or imino acids or esters are useful as hypotensive agents.
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