Wansheng Yu

The asymmetric synthesis of Sitagliptin, a selective dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes

An efficient asymmetric synthesis of Sitagliptin, a new DPP-IV inhibitor for the treatment of type 2 diabetes mellitus has been developed. The beta-amino acid fragment of Sitagliptin was prepared by asymmetric Michael addition of the corresponding α, β-unsaturated ester to (R)-(α-methylbenzyl)benzylamine followed by a two-step elaboration to obtain N-boc beta-amino ester. Hydrolysis of the ester and coupling with the triazolopiperazine afforded Sitagliptin after cleavage of the N-boc group and salt formation. The overall yield was 31% over nine steps.

The synthesis of a chiral β-amino acid derivative by the Grignard reaction of an aspartic acid equivalent

A novel synthetic route to chiral β-amino acid derivative has been developed by a Grignard reaction of 2,4,5-trifluo-rophenyl magnesium bromide with the Weinreb amide derivative of L-aspartic acid. The aspartic equivalent was synthesised from L-aspartic acid in four steps, and the Grignard reagent was prepared by Br–Mg-exchange reaction. The target compound was achieved after the Grignard reaction and a subsequent reduction. Tthe stereo structure of the chiral amine was well preserved from the L-aspartic acid.

Synthesis of a chiral β-amino acid derivative by a cobalt-catalysed coupling reaction

A chiral β-amino acid derivative was synthesised by a cobalt-catalysed alkylation of 2,4,5-trifluorophenyl magnesium bromide with the alkyl halide derivative of L-aspartic acid, using an efficient catalytic reagent: CoCl2/TMEDA. The halide derivative was synthesised from protected L-aspartic acid β-methyl ester and the Grignard reagent was made by bromine- magnesium exchange. The stereo-structure was well preserved from L-aspartic acid.

Efficient Synthesis of 3-R-Boc-amino-4-(2,4,5-trifluorophenyl)butyric Acid

Abstract 3-R-Boc-amino-4-(2,4,5-trifluorophenyl)butyric acid (9) was obtained from L-methionine in six steps with a total yield of 32%. The α-amino acid segment of L-methionine was transferred to chiral aziridine by amino protection, reduction, hydroxyl derivation, and cyclization. After ring opening of 2,4,5-trifluoro-phenyl magnesium bromide, the methylthiomethyl group was then hydrolyzed to β-amino alcohol and oxidized to the target β-amino acid. GRAPHICAL ABSTRACT

A novel method for the synthesis of 2-(3-hydroxy-1-adamantyl)-2-oxoacetic acid

A simple and efficient synthetic route to 2-(3-hydroxy-1-adamantyl)-2-oxoacetic acid is described by a direct oxidation reaction of adamantan-1-yl-ethan-1-one which could be prepared by a Grignard reaction. In this approach, the oxidation reaction introduced the hydroxyl and carboxyl group by a one-pot reaction.