Spirchostatin A (1), isolated from the Pseudomonas sp., is a potent histone deacetylase inhibitor. Therefore, 1 is anticipated to be a promising new agent for cancer chemotherapy. We envisioned that 1 would be elaborated through the twofold macrocyclization of the disulfide 2 possessing the requisite carbon framework, functional groups, and asymmetric carbons. At first, we conducted the synthesis of the segments 3 and 4, which were then subjected to the critical cross coupling reaction. The disulfide bond formation between 3 and 4 proceeded smoothly, and the desired cross coupling product 2 was obtained preferentially. We next investigated the construction of the macrolactam ring. After deprotection of the Boc group and hydrolysis of the methyl ester moiety, the intramoleculer cyclyzation of 10 was carried out using PyBOP, which successfully led to the desired macrolactam 11, a potential key precursor for 1.
