Studies on the Mechanisms of Protein Phosphatase Inhibitor Tautomycin

1)合成了包括互变霉素C-19至C-25部分的降解产物。3）在三氟化硼乙醚络合物存在下，通过环氧化物与砜碳负离子反应，合成了互变霉素C26 ~ C1位的A、B、C三个片段。采用改进的Yamaguchi酯化法实现了A链段和B/C链段的偶联反应。4）通过分子力学计算和高场核磁共振技术确定了互变霉素在溶液中的立体化学结构; 5）通过测定化学合成的互变霉素衍生物的活性，确定了影响互变霉素抑制活性的关键官能团。

1) Degradation product including the moiety for C-19 through to C-25 of tautomycin were synthesized. This synthesis confirmed the relative stereochemistry at C-23 and C-24 of tautomycin.2) We have accomplished the stereoselective synthesis of three segments A,B,C which were derived by retrosynthetic analysis of tautomycin.3) Segment B/C corresponding to the C26 through to the C1 positions of tautomycin was synthesized by the reaction of epoxide with sulfone carbanion in the presence of boron trifluoride etherate. Conpling reaction of Segment A and Segment B/C was achieved by modified Yamaguchi esterification method. Transformation of the furan ring into the maleic anhydride and removal of the protecting groups completed the total synthesis of tautomycin.4) The stereochemistry of tautomycin in solution has been confirmed by employing molecular mechanistic calculation and high-field NMR technique.5) The crucial functionality of tautomycin for the inhibitory activity has been determined by measuring the activity of the of tautomycin derivatives prepared by chemical synthesis.