The first total synthesis of polyketide natural product cryptosporiopsin A (1) was described. It has been accomplished in 12 longest linear steps with 15.4% overall yield starting from enantiomerically pure epoxide 12 prepared by hydrolytic kinetic resolution. Other key steps were Stille coupling, Grignard reaction, De Brabander's esterification and ring closing metathesis (RCM) reaction.