Total Synthesis of Cryptophycin A and Analogs

摘要

The cryptophycins are antimitotic, cyanobacterial metabolites isolated from a blue- green algae. In vivo studies showed that the cryptophycins are active against breast, pancreatic and colon tumors, and retain their potency against the multi-drug resistant cancer cell lines. Total synthesis of two arenastatin A analogues containing the inverted C3 center were completed and preliminary biological testing of one of these isomers was conducted. The results revealed that the natural C3 S configuration is required for pM activity. Total synthesis of arenastatin A and four C10 analogues was completed and biological testing of analogues was conducted. Biological activity of the C10 analogues suggests that there is a specific interaction between the C3' site in the C10 side chain and cryptophycin's binding site.