Synthesis of the lactone core 17 of 8-epi-griseoviridin is reported. Thioethynyl derivative 11 was easily prepared via an anionic coupling reaction between acetylenic compound 9 and sulfone 10. After desilylation of 11, saponification of the resulting hydroxy ester 12 followed by a Mitsunobu macrolactonization furnished the unusual triple-bond-containing nine-membered lactone 13 in 50% yield for the last two steps (39% after recrystallization). Stannylation under Magriotis conditions led to the pure regio- and stereocontrolled vinyltin 14 (80% yield). After a Sn/I exchange, palladium-catalyzed carbonylation delivered either the ester lactone 16 in 67% yield or the propargyl amide 17 in 65% yield. Synthesis of propargyl amide 17 of the lactone core of 8-epi-griseoviridin was achieved in 11.9% overall yield from commercial L-cystin dimethyl ester (nine steps).

The synthesis of the S1-N10 nine-membered lactone core 28 of ent-griseoviridin is reported. Starting from cystine derivative 25, encompassing a terminal ynoate, treatment under Zn/ AcOH conditions led to the formation of lactone 28 in 12% yield. Therefore, the lactone moiety of ent-griseoviridin is obtained in 10.7% overall yield for two steps. An access to the corresponding 5-epi-griseoviridin lactone 29 is also described.