Studies on the Mechanisms of Protein Phosphatase Inhibitor Tautomycin

1)合成了他霉素C-19 ~ C-25的降解产物。该合成证实了他霉素在C-23和C-24位点的相对立体化学性质。2)通过对他霉素的反合成分析，我们完成了A、B、C三个片段的立体选择性合成。3)在三氟化硼醚存在下，环氧化物与砜碳离子反应合成了他霉素C26至C1位对应的B/C段。采用改进的山口酯化法实现了A段与B/C段的偶联反应。呋喃环转化为马来酸酐并去除保护基团完成了他霉素的全合成。4)通过分子力学计算和高场核磁共振技术，确定了他霉素在溶液中的立体化学。5)通过测定化学合成的他霉素衍生物的活性，确定了他霉素抑制活性的关键功能。

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.