Transfer hydrogenation of cyclopamine analogs

摘要

Provided herein is a process for the transfer-hydrogenation of ketone analogs of members of the jervine type of Veratrum alkaloids, such as cyclopamine. Also provided herein are novel ruthenium transfer-hydrogenation catalysts.

主权项

1. A process for preparing a compound of formula II-a: or a pharmaceutically acceptable salt form thereof; from a compound of formula I-a: or a pharmaceutically acceptable salt form thereof; wherein:
R1 is H or a nitrogen protecting group; the process comprising reacting a compound of formula (I-a) or a pharmaceutically acceptable salt form thereof with a hydrogen donor selected from the group consisting of methanol, ethanol, isopropanol, and t-butanol, in the presence of a ruthenium transfer-hydrogenation catalyst of formula (iii-a): wherein Ra and Rb are both either H or methyl; and
Rc is either H or C1-6 alkyl; to thereby provide a compound of formula (ii-a) or a pharmaceutically acceptable salt form thereof in a diastereomeric excess of greater than about 90% to about 99.5%.