Efficient Generation of a Trisporoid Library by Combination of Synthesis and Biotransformation

摘要

Trisporic acids and their biosynthetic precursors represent a family of powerful fungal pheromones and morphogenetic factors. A highly flexible synthetic protocol is described that (ⅰ) provides rapid access to nonfunctionalized early trisporoids from β-ionone, (ⅱ) includes a regiospecific oxidative functionalization of β-ionone leading to 1-acetoxy-β-ionone giving access to functionalized trisporoids, and (ⅲ) utilizes a biotransformation of early synthetic trisporoids by growing cells of Blakeslea trispora to prepare late trisporoids including trisporic acids. The same protocol also provides deuterium-labeled trisporoids such as trisporin B [~2H_3]-19. Administration of [~2H_3]-19 to growing cells of the (-)-mating type of B. trispora resulted in the formation of the labeled trisporols [~2H_3]-20 and [~2H_3]-21. Growing cultures containing both mating types can be used to prepare trisporic acids from early precursors.