65(P1-13) エポキシアルコールのハロゲン求核剤による選択的開環反応とそのダクチリン合成への応用(ポスター発表の部)  [in Japanese] 65(P1-13) REGIOSELECTIVE RING OPENINGS OF EPOXY ALCOHOLS WITH HALOGEN-NUCLEOPHILES AND THEIR APPLICATION TO DACTYLYNE SYNTHESIS  [in Japanese]

Dactylyne (1) and its isomer, isodactylyne (2), isolated from the sea hare Aplysia dactylomela, are characterized structurally by a tetrahydropyran ring with all α-oriented, four substituents, (2E)-3-bromo-2-pentenyl and pentenynyl groups at C-2 and C-6, and bromine and chlorine atoms at C-3 and C-5, and prossess central nervous system depressent activity, as evidenced by the potentiation of pentobarbital hypnosis. In view of the structural features and the biological activity, these are attractive synthetic targets. In the course of the synthetic studies on these natural products, we found that dialkylamine hydrohalides are much more effective as sources of halide nucleophiles for titanium-mediated ring openings of 2,3- and 3,4-epoxy-1-ols at the 3- and 4-positions, respectively. Interestingly, diethylaluminium chloride was found to be also effective for the regioselective opening of trans-2,3-epoxy-1-01 (6) at the 3-position. We describe herein the details of these results in Figures 1 and 2. Next, we describe application of our procedures to the synthetic approaches towards optically active 1 and 2 in Schemes 2 and 3. Starting with 3-butyn-1-01, we derived the optically pure epoxy alcohol (16), which was intramolecularly cyclized on acid treatment to give smoothly the synthetic key intermediate (22).