Search

A chemoenzymatic synthesis of the veterinary antibiotic florfenicol is described. The key step involves the dynamic reductive kinetic resolution (DYRKR) of a keto ester by using a ketoreductase‐02 (KRED‐02) to afford the two contiguous stereocenters of the (2S,3R)‐cis‐1,2‐amino alcohol intermediate in >99 % ee and a diastereomeric ratio (dr) of 99 %. This green biocatalysis is environmental friendly with high enantioselectivity and product yields. Two methods for the nucleophilic fluorination step involved the use of aziridines and cyclic sulfates to safely prepare fluoroamines with high regioselectivity. Additional studies have indicated that KRED‐02 can also be used to afford chiral alcohol (S)‐21 in good yields with high enantioselectivity. This study shows that the integration of biocatalysis into organic synthesis can be useful and provide industrial opportunities for applications of florfenicol. [ABSTRACT FROM AUTHOR]

This communication describes a synthetic study of the originally proposed structure of mycalol (1) and the total synthesis of the actual structure of the anticancer marine natural product mycalol (2). The total synthesis of the originally proposed structure of mycalol (1) was targeted by a late-stage asymmetric dihydroxylation, which resulted in an inseparable mixture of diastereomers. Thus a new strategy was developed for the total synthesis of the revised structure of mycalol (2); all the stereocentres except the C-2'-OH were created in an asymmetric fashion by using a Maruoka allylation, a Noyori asymmetric reduction, and an asymmetric alkynylation. [ABSTRACT FROM AUTHOR]

Aliskiren is the first-in-class orally active direct renin inhibitor. It was approved in 2007 for the treatment of hypertension. We have designed a new strategy for the convergent synthesis of aliskiren that involves a catalytic stereoselective nitroaldol reaction as the key step. A new enantiopure nitroalkane (synthon A1), prepared in only three steps from a commercially available enantiopure 2-(arylmethyl)-3-methyl butanol derivative, was successfully used in a copper-catalysed Henry reaction to give a nitrolactone intermediate in which the correct configuration for the final product was established at all four stereocentres. Nitro-group reduction, Boc-protection of the resulting amine, aminolysis of the lactone with 3-amino-2,2-dimethylpropionamide, and finally Boc-deprotection led to the enantiopure renin inhibitor aliskiren. [ABSTRACT FROM AUTHOR]

"One advice that I give my students is to try and understand reaction mechanism." Find out more about this author's research at https://doi.org/10.1002/ejoc.201801115. "One advice that I give my students is to try and understand reaction mechanism." Find out more about this author's research at https://doi.org/10.1002/ejoc.201801115. [ABSTRACT FROM AUTHOR]