Peuchmaur Marine, Wong Yung-Sing
Département de Pharmacochimie Moléculaire, UMR 5063 CNRS/Université Joseph Fourier, ICMG FR 2607 CNRS, Bâtiment E, Bâtiment André Rassat, 470 rue de la Chimie, 38 041 Grenoble cedex 9, France.
J Org Chem. 2007 Jul 6;72(14):5374-9. doi: 10.1021/jo0707986. Epub 2007 Jun 12.
We report concise and stereocontrolled syntheses of aculeatins (-)-A, (+)-B, (+)-D, and (+)-6-epi-D. Diastereodivergent 1,3-inductions in Mukaiyama aldol coupling contribute to reduce steps and to increase flexibility with reactants having sterically restricted proximal substituents (i.e., CH2), involving either a good anti or a moderate syn 1,3-induction, depending on the nature of protecting group (P). In addition, the 3,5-syn-diol-ketone resulting from concomitant deprotection of the beta-alkoxy (Tr = trityl) group proves to be remarkably stable whereas the 3,5-anti diastereoisomer cyclizes spontaneously to the corresponding tetrahydropyran hemiketal, thus enabling a useful and facile separation. The second part of our study is devoted to improving the yield and the diastereoselectivity of the final phenolic oxidation reaction leading to aculeatins.
我们报道了短小尖腹蜂毒素（-）-A、（+）-B、（+）-D和（+）-6-表-D的简洁且立体可控的合成方法。在向山羟醛缩合反应中的非对映发散性1,3-诱导作用有助于减少步骤，并增加与具有空间位阻近端取代基（即CH2）的反应物的灵活性，这涉及良好的反式或中等程度的顺式1,3-诱导，具体取决于保护基团（P）的性质。此外，由β-烷氧基（Tr = 三苯甲基）基团的同时脱保护产生的3,5-顺式二醇-酮被证明非常稳定，而3,5-反式非对映异构体则自发环化形成相应的四氢吡喃半缩酮，从而实现了有效且简便的分离。我们研究的第二部分致力于提高导致短小尖腹蜂毒素的最终酚氧化反应的产率和非对映选择性。
