Total Synthesis of the GRP78-Downregulatory Macrolide (+)-Prunustatin A, the Immunosuppressant (+)-SW-163A, and a JBIR-04 Diastereoisomer That Confirms JBIR-04 Has Nonidentical Stereochemistry to (+)-Prunustatin A

A unified total synthesis
of the GRP78-downregulator (+)-prunustatin
A and the immunosuppressant (+)-SW-163A based upon [1 + 1 + 1 + 1]-fragment
condensation and macrolactonization between O(4) and C(5) is herein
described. Sharpless asymmetric dihydroxylation was used to set the
C(2) stereocenter present in both targets. In like fashion, coupling
of the (+)-prunustatin A macrolide amine with benzoic acid furnished
a JBIR-04 diastereoisomer whose NMR spectra did not match those of
JBIR-04, thus confirming that it has different stereochemistry than
(+)-prunustatin A.