Asymmetric total synthesis of dendrobatid alkaloids: preparation of indolizidine 251F and its 3-desmethyl analogue using an intramolecular Schmidt reaction strategy.
Asymmetric total synthesis of dendrobatid alkaloids: preparation of indolizidine 251F and its 3-desmethyl analogue using an intramolecular Schmidt reaction strategy.
复制标题
DOI：
10.1021/ja0320018
复制
发表时间：
2004-04
影响因子：
15
通讯作者：
Aaron D. Wrobleski;K. Sahasrabudhe;J. Aubé
中科院分区：
文献类型：
--
作者：
Aaron D. Wrobleski;K. Sahasrabudhe;J. Aubé
报道了从棉铃蛙皮肤提取物中提取的天然产物251F(1)及其外消旋3-脱甲基衍生物(2)的全合成。Diels-Alder反应启动了这两个合成，并建立了四个连续的立体合成中心。对2的合成很重要的是第一代臭解/烯化/羟醛反应策略，将[2.2.1]双环酸转化为[3.3.0]双环辛烷二喹4b。进一步阐述适当的酮叠氮化物允许关键的分子内施密特反应来提供目标分子的三环核心。在第二代方法中，串联的开环/闭环易位反应影响了整个[2.2.1]-->；[3.3.0]骨架重排以产生二喹烷4a。以类似的方式，4a被操纵到合适的酮叠氮化物，分子内的Schmidt反应产生了251F的核心环状结构。
Total syntheses of alkaloid 251F (1), a natural product detected from the skin extracts of the dendrobatid frog species Minyobates bombetes, and its racemic 3-desmethyl derivative (2) are reported. A Diels-Alder reaction initiated both syntheses and established four consecutive stereogenic centers. Important to the synthesis of 2 was a first-generation ozonolysis/olefination/aldol strategy to convert a [2.2.1] bicyclic acid to the [3.3.0]bicyclooctane diquinane 4b. Further elaboration to an appropriate keto azide allowed for a key intramolecular Schmidt reaction to deliver the tricyclic core of the target molecule. In a second-generation approach, a tandem ring-opening/ring-closing metathesis reaction effected an overall [2.2.1] --> [3.3.0] skeletal rearrangement to deliver diquinane 4a. In similar fashion, 4a was manipulated to an appropriate keto azide, and an intramolecular Schmidt reaction generated the core cyclic architecture of 251F.