Asymmetric synthesis of phthalascidin, zalypsis and renieramycin T from N-Cbz-L-tyrosine

Abstract

A new practical synthesis of Pt-650, zalypsis and renieramycin T is achieved by employing a Pictet−Spengler cyclization coupling of the tetrahydroisoquinoline and phenylalaninol partners with good yield and reproducibility, in which both the two coupling partners are prepared by a common route. Moreover, a one-pot Mitsunobu displacement/photolysis sequence of methoxyquinone alcohol intermediate implements the introduction of the amino functionality at C-22 and A-ring modification in one step. By the approach, Pt-650, zalypsis and renieramycin T are synthesized with 21–24 total synthetic steps from N-Cbz-l-tyrosine in good overall yield respectively.