47(PA1-5) フラノセンブラノリドの合成研究(ポスター発表の部)

抄録

As the course of the studies directed to the synthesis of lophotoxin 1, a novel neuromuscular toxin of marine origin, we have explored an approach for the construction of the macro ring system characteristic for the furanocembranolides. 1. Macrocyclization utilizing the furan ring formation reaction Our strategy is to effect the furan ring formation and macrocyclization at the same time by using the trisubstituted furan ring synthesis of P. H. Williams et al. and this has been tested on the synthesis of a model system 3.(Scheme 1) The acyclic precursors 7E and 7Z were prepared through the coupling of segments 5 and 6, which were obtained efficiently by the steps shown on Schemes 2 and 3, followed by chromatographic separation. After conversions to 8E and 8Z respectively, the macrocyclization were performed as acetic acid solution at the presence of a catalytic amount of piperidine at 50℃. In the E series the cyclization product 9E was obtained as a diastereomeric mixture in 40% overall yield from 7E, while in the reaction of 8Z the intramolecular Diels-Alder products 10a and 10b of intermediary cyclization product 9Z were charactetrized. 2. Synthesis of deisopropenylpukalide 11 The synthesis of more advanced model compound 11 was studied. The left-hand segment 15 was prepared from D-glutamic acid. (Scheme 4) The coupling of 15 with the phosphonate 6b yielded 16 stereospecifically which was converted to 17 and cyclized to give 18 under lactone ring formation.