38 AN APPROACH TO TOTAL SYNTHESIS OF ENMEIN

Abstract

A total synthesis of enmein (1) through a main route shown in Chart 1 has been attempted. As an important key intermediate, compound 10 was chosen. In this compound, the stereochemistry is identical with that of enmein, in the asymmetric centers, C-5, C-8, C-9, C-10, and C-13. First, we converted enmein into compound 21 via several steps of reactions, as shown in Chart 2. Acyloin condensation with 20 or 21 gave 22, whose Wolff-Kishner reaction (Nagata's modification) yielded the desired compound 10. The yield of each step was satisfactory. Subsequently, we carried out the transformation of 10 into enmein. As shown in Chart 3, we succeeded in this transformation under paying attention to the stereochemistry of the asymmetric centers, C-1, C-3, and C-6. Except a few steps, the yields were good. Especially, it is noteworthy that a stereoselective cyclization of ketal carboxylic acid 11 into enmein-type compound 12 proceeded in 72% yield. The last object is synthesis of compound 10. We synthesized compound 53 from the starting material 51. Stereoselective construction of ring D and migration of the double bond to C-6: C-7 are the remaining significant problems which must be challenged.