Total Synthesis of the Proposed Microcyclamides MZ602 and MZ568

The
first convergent total synthesis for the proposed structures
of microcyclamides MZ602 (1) and MZ568 (2) has been accomplished in 11 linear steps with 12.5 and 16.8% overall
yield, respectively. Key features of the syntheses include a one-pot
cascade reaction to construct core Boc-l-Ile-Thz-OAllyl fragment 5, and a removable pseudoproline (ΨMe,Me pro)
inducer assisted cyclization of thiazole-containing all-l linear peptides. The spectral data (1H NMR, 13C NMR, and HRMS) of synthetic MZ602 (1) were quite similar
to those of the proposed natural microcyclamide MZ602, except to an
opposite sign of the optical rotation value. Surprisingly, the synthetic
MZ568 (2) presented large discrepancies in characteristic
spectral data from those of the reported natural product, although
the absolute configuration of key intermediate 36 was
unambiguously determined by single-crystal X-ray analysis in our work.
These findings revealed that the proposed structures of natural microcyclamides
MZ602 and MZ568 required revision.