30 光学活性アンスラサイクリノンの不斉合成

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概要

• 論文の詳細を見る

• Preparation of optically active anthracyclinones(2), the aglycones of anthracycline antibiotics(1) showing promising anticancer activities, was attempted by employing two different types of asymmetric syntheses. Thus, the asymmetric bromolactonization of (S)-N-(α,β-unsaturated) acylprolines ((S)-13) was found to give the bromolactones(14) in which one diastereomer(14A) was highly predominant. Further chemical elaborations of 14 including debromination and hydrolytic cleavage of the (S)-proline moiety afforded (R)-α-hydroxy acids((R)-16). (R)-16a,b were converted to (R)-α-hydroxy ketone((R)-9a), 92%ee, a model compound of the AB ring system of 2, and (R)-9b, 100%ee, one of the most versatile synthetic intermediates for 2, respectively. On the other hand, the chiral hydride prepared by partially decomposing lithium aluminum hydride with (-)-N-methylephedrine(1eq) and N-ethylaniline(2eq) was found to reduce the methyl ketone (24) highly stereoselectively, giving (S)-allyl alcohol((S)-25), 92%ee, in a quantitative yield. Optically pure (S)-25 obtained in 87% yield based on 24 by recrystallization, was elaborated to (R)-9b, 100%ee, by successive epoxidation, reduction, and oxidation. (R)-α-Hydroxy ketone((R)-9b) was further transformed to (R)-9c, the synthetic intermediate of 2e, the aglycone of 1e having improved therapeutic properties. Based on the above studies, it became possible to prepare various types of 2 by asymmetric synthesis.

• 天然有機化合物討論会の論文
• 1980-09-10

著者

• Koga Kenjiro

  Department Of Pharmaceutics Faculty Of Pharmaceutical Sciences Hokuriku University

• 古賀 憲司

  東大薬

• 寺島 孜郎

  (財)相模中央化学研究所

• 寺島 孜郎

  Faculty Of Pharmaceutical Sciences University Of Tokyo:(present Address)sagami Chemical Research Cen

• 朱 尚渉

  東大薬

• 丹野 紀彦

  Faculty Of Pharmaceutical Sciences University Of Tokyo

• 寺島 孜郎

  東大薬

• 丹野 紀彦

  東大薬

関連論文

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