73 立体特異的1,2転位反応を基盤とするマクロリド合成

概要

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Stereocontrolled approaches to two mycinamicin-type macrolides, protomycinolide IV (1) and mycinolide IV (2), are described. The key feature is the chirality transfer methodolgy based on the stereospecificity of the Lewis acid-promoted 1,2-rearrangements in the acyclic systems. Stereo-convergent asymmetric total synthesis of 1 was achieved via organoaluminum-promoted asymmetric pinacol-type rearrangement. Two chiral fragements, C(1)-C(9) and C(11)-C(17) portions, were constructed from a common chiral starting material, (S)-ethyl lactate. High diastereoselectivity of the nucleophilic attack on the Me_3Si-bearing β,γ-unsaturated carbonyl compounds was used for the establishment of the relative stereochemistries. For the control of Me substituent at C(8), two methods were devised; (i) equilibration of δ-lactone and (ii) acid-catalyzed stereoselective cyclization of ketene dithioacetal possessing an internal OH group. Consideration of the common skeletons of 1 and 2 led us to a similar synthetic plan of the latter macrolide. The requisite chiral C(10)-C(17) fragment was prepared from the chiral glycerol derivative via the pinacol-type rearrangement. Another effective approach to this segment was enabled by the use of 1,2-rearrangement of chiral epoxyalcohol derivatives, newly developed for the present purpose. Non-chelation controlled aspects of α-vinyl β-hydroxy carbonyl compounds were also noted.
天然有機化合物討論会の論文
1986-09-09