In a continuation of our synthetic studies on clerodane diterpenoids, we deal in the present paper with the asymmetric synthesis of (-)-kolavenic acid, which represent the first of its kind in the synthesis of clerodane diterpenoids, and the synthesis of agelasins, which are structurally featured by the presence of 9-methyl-7-adenylium moiety and biologically active. 1. Asymmetric synthesis of the octalon intermediate 1a. The octalon derivative 1a has been demonstrated to be a versatile intermediate in our syntheses of clerodane diterpenoids and we investgated first the chiral synthesis of 1a. This has been realized by the application Ender's asymmetric alkylation. 6-Methyl-2-cyclohexenone 5, thus obtained in 100% ee by a choice of the alkylating agent, was converted to (10R)-1a, [α]_D, +16°. (Scheme 1) 2. Total synthesis of (-)-kolavenic acid 2. The chiral 1a, prepared above, was transformed to kolavenal 10, [α]_D) 60°by 10 steps procedure (Scheme 2), which was confirmed to be identical in all respects, including the optical rotation, with the authentic specimen derived from natural 2. The conversion of 10 to 2 was also performed. 3. Synthesis of agelasins. The selective alkylation of the 9-methyl-adenine ring at 7 position was feasible by the application of Fujii's procedure, which make use of N^6-methoxy derivative. The demethoxylation of the alkylated products was performed with treatment of zinc/aqueous acetic acid. This method culiminated in the synthesis of agelasin B 3 from kolavenyl bromide 16. (Scheme 4)
