Synthesis of New unnatural Macrocyclic Trichothecenes: 4-epiverrucarin A. 47th Communication on verrucarins and roridins

The 4‐epiverrucarin A (24), a new unnatural macrocyclic trichothecene, was synthesized starting from 4‐epiverrucarol (20). The latter was obtained by metal‐hydride reduction of the 4‐oxo derivative 19. Subsequent conversion of 20 into the monoester 30 and then the diester 32 followed by macrolactonization of the latter yielded 4‐epiverrucarin A (24). Attempts to invert the configuration of the naturally occuring 3α‐OH group of a trichothecene were unsuccessful. The cytostatic (P‐815) and immunosuppressive (MLR) activity of several natural and unnatural trichothecenes was determined in vitro.