Related Experiment Videos
Analogs of cyclosporin A modified at the D-Ala8 position
A A Patchett1, D Taub, O D Hensens
1Merck, Sharp & Dohme Research Laboratories, Rahway, New Jersey 07065.
The Journal of Antibiotics
|January 1, 1992
Abstract:
The conversion of [2-deutero-3-fluoro-D-Ala8]cyclosporin A (1) to a dehydroalanine analog [delta-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.