Work

A General and Enantioselective Approach to Pentoses: A Rapid Synthesis of PSI-6130, the Nucleoside Core of Sofosbuvir

Year: 2014

Type: article

Abstract: An efficient route towards biologically relevant pentose derivatives is described. The de novo synthetic strategy features an enantioselective α-oxidation reaction enabled by a chiral amine in conjunction with copper(II) catalysis. A subsequent Mukaiyama aldol coupling allows for the incorporation of a wide array of modular two-carbon fragments. Lactone intermediates accessed via this route provide a useful platform for elaboration, as demonstrated by the preparation of a variety of C-nucleosides and fluorinated pentoses. Finally, this work has facilitated expedient syntheses of pharmaceutically active compounds currently in clinical use.

Source: Journal of the American Chemical Society

DOI: 10.1021/ja502205q

Authors: Manuel Peifer, Raphaëlle Berger, Valerie W. Shurtleff, Jay C. Conrad, David W. C. MacMillan

Institution: Princeton University

Language: English

Topic: Asymmetric Synthesis and Catalysis

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: hybrid

Estimated APC paid: $4,500

Funder: National Institute of General Medical Sciences