TOTAL SYNTHESIS OF CRYPTOPHYCINS AND THEIR 16-(3-PHENYLACRYLOYL) DERIVATIVES

Cryptophycin A, a cyclic depsipeptide isolated from the blue-green alg a (cyanobacterium) Nostoc sp.GSV 224, has shown excellent activity aga inst solid tumors implanted in mice. The benzylic epoxide, which was s hown to be very important for biological, activity, is also fairly uns table under both acidic and alkaline conditions. The high doses needed to observe in vivo activity might be a result of this instability. In order to solve this problem while preserving the electrophilic charac ter of the benzylic position, enones 1 and 2 have been proposed as pro mising analogs of the natural product, and a convergent total synthesi s of these compounds is described. In addition, the same strategy was used to prepare Cryptophycins A, B, C, and D.