A Convergent Route for the Total Synthesis of Malyngamides O, P, Q, and R

A convergent, enantioselective and general synthetic route to a class of marine natural products-malyngamides O(1), P(2), Q(3), R(4), 5 ''-epi-3 and 5 ''-epi-4-bearing a novel vinyl chloride structural motif was developed. The key steps involved construction of the vinyl chloride functionality by Wittig reaction, a DCC/HOBt-promoted amidation, an aldol reaction in the construction of the basic backbone of 1, 2, 3, 4, 5 ''-epi-3, and 5 ''-epi-4, and methylation of an enol moiety via either base/acid conditions or a Mitsunobu reaction. Moreover, the absolute configuration of the stereogenic center at C-5 '' in 3 was further confirmed by synthesis of the natural product and its C-5 '' epimer.