1 research outputs found
Total Synthesis and Determination of the Absolute Configuration of Rakicidin A
Rakicidin
A is a cyclic depsipeptide that has exhibited unique
growth inhibitory activity against chronic myelogenous leukemia stem
cells. Furthermore, rakicidin A has five chiral centers with unknown
stereochemical assignment, and thus, can be represented by one of
32 possible stereoisomers. To predict the most probable stereochemistry
of rakicidin A, calculations and structural comparison with natural
cyclic depsipeptides were applied. A total synthesis of the proposed
structure was subsequently completed and highlighted by the creation
of a sterically hindered ester bond (C1–C15) through trans-acylation
from an easily established isomer (C1–C13). The analytic data
of the synthetic target were consistent with that of natural rakicidin
A, and then the absolute configuration of rakicidin A was assigned
as 2<i>S</i>, 3<i>S</i>, 14<i>S</i>,
15<i>S</i>, 16<i>R</i>. This work suggests strategies
for the determination of unknown chiral centers in other cyclic depsipeptides,
such as rakicidin B, C, D, BE-43547, and vinylamycin, and facilitates
the investigations of rakicidin A as an anticancer stem cell agent