Skaanderup Philip R, Madsen Robert
Department of Chemistry, Building 201, Technical University of Denmark, DK-2800 Lyngby, Denmark.
J Org Chem. 2003 Mar 21;68(6):2115-22. doi: 10.1021/jo020645c.
An efficient strategy is described for the synthesis of enantiopure calystegine alkaloids. The key step employs a zinc-mediated fragmentation of benzyl-protected methyl 6-iodo-glycosides followed by in situ formation of the benzyl imine and Barbier-type allylation with zinc, magnesium, or indium metal. Stereochemistry in the pivotal allylation is controlled by the choice of the metal. The functionalized 1,8-nonadienes, thus formed, are converted into cycloheptenes by ring-closing olefin metathesis. Regioselective hydroboration and oxidation give the corresponding cycloheptanones, which are deprotected to afford the desired calystegines. Hereby, calystegine B(2), B(3), and B(4) are prepared from D-glucose, D-galactose, and D-mannose, respectively. This route constitutes the shortest synthesis of calystegine B(2) and gives rise to the first total syntheses of calystegine B(3) and B(4).
描述了一种用于合成对映体纯的旋花茄生物碱的有效策略。关键步骤是利用锌介导的苄基保护的6-碘甲基糖苷的碎片化反应,随后原位形成苄基亚胺,并与锌、镁或铟金属进行巴比耶型烯丙基化反应。关键烯丙基化反应中的立体化学通过金属的选择来控制。由此形成的官能化1,8-壬二烯通过闭环烯烃复分解反应转化为环庚烯。区域选择性硼氢化和氧化反应得到相应的环庚酮,将其脱保护即可得到所需的旋花茄碱。据此,分别由D-葡萄糖、D-半乳糖和D-甘露糖制备了旋花茄碱B(2)、B(3)和B(4)。此路线构成了旋花茄碱B(2)最短的合成方法,并首次实现了旋花茄碱B(3)和B(4)的全合成。