The chemistry of ascomycin: Structure determination and synthesis of pyrazole analogues

Ascomycin (1) is a close analogue of the immunosuppressant FK-506 (2) which differs slightly in the side chain at position 21 (ethyl vs allyl). Structurally unique ascomycin and FK-506 are the subjects of intense chemical research because of their application in organ transplantation and autoimmune disease. We have been interested in studying the effect of structural modification and conformational change on biological activity. This paper reports the fermentation and structural determination of ascomycin as well as the synthesis and structure confirmation of a series of pyrazole analogues (3 and 4) derived from ascomycin.