16 不斉環化反応による抗腫瘍性抗生物質Bactobolin骨格の高立体選択的合成

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Bactobolin (1a), a new congener of actinobolin (1b), was recently isolated from the culture broths of a Pseudomonas sp.^<1,2> These antibiotics 1a and 1b have a common bicyclic skeleton but differ considerably in their biological activity, especially in antitumor activity, the former being much stronger than the latter. We wish to report here a highly stereoselective synthesis of the common skeleton 17 by the intramolecular Diels-Alder reaction of the triene 3 containing (Z)-diene and an asymmetric carbon at the pentadienylic position. Our synthetic strategy is based on the following considerations: (1) the intramolecular Diels-Alder reaction of a (Z)-diene will occur from a single diastereomeric face of the dienophile, (2) a desirably bulky substituent (a chiral center) at the pentadienylic position will further amplify to select a preferred single transition state by substantial nonbonded interactions with the terminal vinyl group of the diene, (3) thus the chiral diene derived originally from L-threonine will give the desired asymmetric carbons through the key reaction, (4) Iodolactonization and transformation of γ-lactam 2 to δ-lactone 15 will afford the common precursor to 1a and 1b. The experimental results showed that a series of reactions proceeded efficiently and the stereochemistry of a product 18 was established by X-ray analysis.
天然有機化合物討論会の論文
1982-09-10