17 カリクリン類の合成研究(口頭発表の部)

抄録

Calyculins (1) isolated from the marine sponge Discodermia calyx have strong cytotoxic activity and calyculin A has been revealed to be an inhbitor of protein phosphatases 1 and 2A. The relative stereostructures of calyculins have been determined by X-ray diffraction studies and their absolute configurations have been depicted as the structures 1 by CD spectral studies of the C_<33>-C_<37> unit. We have provided conclusive evidence supporting the reported absolute configurations of calyculins by the synthesis of the C_<33>-C_<37> unit. The intriguing biological activities of calyculins coupled with their structural curiosities have led us to investigate the total synthesis of calyculins. Retrosynthetic analysis has revealed that 1 would be constructed from four fragments A, B, C, and D, shown in Scheme 1. Fragment A could be prepared by use of the Stille coupling of the vinyl iodide unit 4 with the nitrile unit 3 followed by converting to the vinyl iodide function according to the Barton's procedure. Fragment C have been prepared by the oxazoline formation of the N-acylserine (21, 27) and the subsequent oxidation of the oxazoline. Synthesis of fragment D has been accomplished from (S)-serine using osmium tetroxide mediated dihydroxylation of the Z-olefin. The common northern part 41 of calyculins A, B, E, and F has been synthesized by coupling of the 38 with the 39, followed by N, N-dimethylation.