67 環状エンジイン抗生物質ダイネミシンAとその類縁体の合成研究(ポスター発表の部)

概要

論文の詳細を見る
Recently, a new class of novel antitumor antibiotics possessing an unprecedented bicyclic enediyne unit has been discovered. Dynemicin A (1), a potent antitumor antibiotic, has a novel 10-membered enediyne ring connected to an anthraquinone moiety. Based on the proposed action mechanism of dynemicin A and molecular mechanics calculation, the simplified compound (27) having aniline, epoxide and [7.3.1] tridecadiyne system was designed. The model compound (27) was synthesized from lepidine in 10 steps. Key step was the cyclization with silylacetylene to ketone carbonyl with CsF in the presence of 18-crown-6. Although the synthesized compound was cycloaromatized under acidic condition, the product was pinacol-pinacolone rearrangement product. The synthesized compounds (27,28,31,32) also exhibited DNA cleaving activity. The approach to chiral synthesis of model compound was examined. High diastereoselective method adding magnesium acetylide to 1-(4'-quinoline)ethanol (18) was developed. The starting chiral alcohol, 1-(4'-quinoline)ethanol was prepared by kinetic resolution of racemic alcohol with porcine pancreatin lipase in organic media The anthraquinone moiety in dynemicin A plays an important role as an intercalator to DNA. Diels Alder reaction between naphthoquinone derivatives and diene (49) including D ring, followed by aromatization afforded the tetracyclic aromatic compound 58 (including A, B, C, D ring of dynemicin A), the potential intermediate for introduction of acetylene group in the synthesis of the another model having anthraquinone moiety.
天然有機化合物討論会の論文
1993-09-10

67 環状エンジイン抗生物質ダイネミシンAとその類縁体の合成研究(ポスター発表の部)

スポンサーリンク

概要

著者

関連論文

スポンサーリンク