Stereoselective synthesis of (R)-(−) and (S)-(+)-phoracantholide I from (R)-(+)-γ-valerolactone

Abstract A concise total synthesis of ( R )-(−)-phoracantholide I 1 and ( S )-(+)-phoracantholide I 2 has been developed from ( R )-(+)-γ-valerolactone 6 . The key steps in the synthesis of these macrolides involved enzymatic reduction of Levulinic ester 4 by asymmetric dehydrogenase, Z -selective Wittig reaction of (4-carboxybutyl)triphenylphosphonium ylide 11 with lactol 7 , and cyclization of seco -acid 8 using either a Yamaguchi lactonization protocol or a Mitsunobu protocol to afford ( R )-(−)-phoracantholide I and ( S )-(+)-phoracantholide I respectively.