ANALOGS OF CYCLOSPORIN A MODIFIED AT THE D-ALA8 POSITION

ARTHUR A. PATCHETT; DAVID TAUB; OTTO D. HENSENS; ROBERT T. GOEGELMAN; LIHU YANG; FRANCIS DUMONT; LARRY PETERSON; NOLAN H. SIGAL

doi:10.7164/antibiotics.45.94

ANALOGS OF CYCLOSPORIN A MODIFIED AT THE D-ALA⁸ POSITION

ARTHUR A. PATCHETT, DAVID TAUB, OTTO D. HENSENS, ROBERT T. GOEGELMAN, LIHU YANG, FRANCIS DUMONT, LARRY PETERSON, NOLAN H. SIGAL

Author information

JOURNAL FREE ACCESS

1992 Volume 45 Issue 1 Pages 94-102

DOI https://doi.org/10.7164/antibiotics.45.94

Details

Abstract

The conversion of [2-deutero-3-fluoro-D-Ala⁸]cyclosporin A (1) to a dehydroalanine analog [Δ-Ala⁸]cyclosporin A (2) was achieved with lithium diisopropylamide in THF at low temperature. This dehydro compound is a useful intermediate for the preparation of position 8 analogs of cyclosporin A formed from it by the conjugate addition of thiol compounds. NMR conformational studies have provided evidence for the restoration of D-stereochemistry in the modified Ala⁸ residues. The preparation of several of these cyclosporin analogs and their bioactivities are described.

Corresponding author

Register with J-STAGE for free!