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 condensationand macrolactonization between O(4) and C(5) is hereindescribed. Sharpless asymmetric dihydroxylation was used toset the C(2) stereocenter present in both targets. In like fashion,coupling of the (+)-prunustatin A macrolide amine with benzoicacid furnished a JBIR-04 diastereoisomer whose NMR spectradid not match those of JBIR-04, thus confirming that it hasdifferent stereochemistry than (+)-prunustatin A.

Total Synthesis of the Antitumor Macrolides, (+)-Brefeldin A and 4‑Epi-Brefeldin A from D‑Glucose: Use of the Padwa Anionic Allenylsulfone [3+2]-Cycloadditive Elimination To Construct Trans-Configured Chiral Cyclopentane Systems

A new synthesis of (+)-brefeldin A is reported via Padwa allenylsulfone [3+2]-cycloadditive elimination. Cycloadduct 13 was initially elaborated into iodide
27, which, following treatment with Zn, gave aldehyde 28 whose C(9) stereocenter was epimerized. Further elaboration into enoate 38 and Julia−Kocienski olefination with 5 subsequently afforded 39, which was deprotected at C(1) and O(15). Yamaguchi macrolactonization of the seco-acid thereafter afforded a macrocycle that underwent O-desilylation and inversion at C(4) to give (+)-brefeldin A following deprotection