Approach for expanding triterpenoid complexity via divergent Norrish-Yang photocyclization.
Approach for expanding triterpenoid complexity via divergent Norrish-Yang photocyclization.
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DOI：
10.1021/jo400275p
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发表时间：
2013-04-19
期刊：
影响因子：
--
通讯作者：
Tochtrop GP
中科院分区：
文献类型：
--
作者：
Ignatenko VA;Tochtrop GP
三萜类化合物包括一个非常多样化的多环分子家族，众所周知，它具有无数的药用特性。因此，三萜类化合物是药物化学和多样性合成的一个有吸引力的目标。在构建天然产物样库中，光化学转化为快速、绿色和廉价地产生骨骼多样性提供了一种有前途的工具。考虑到这一点，我们开发了一种以多样性为导向的策略，通过在B/C-环融合时依次进行烯丙基氧化和桥联双键的氧化裂解，将母体三萜酸和羊毛甾醇转化为伪对称聚酮。所得到的聚酮被假设为经过发散的Norrish-Yang环化以产生独特的6/4/8-稠合三萜类似物。母体三萜类化合物之间的细微差异导致了反应功能的空间排列显著不同。这一发现通过构象分析得到了合理的解释，以解释意想不到的光诱导的片拿甲基化，以及所需的诺里什-杨环化的区域和立体化学结果。
Triterpenoids comprise a very diverse family of polycyclic molecules that is well-known to possess a myriad of medicinal properties. Therefore, triterpenoids constitute an attractive target for medicinal chemistry and diversity-oriented synthesis. Photochemical transformations provide a promising tool for the rapid, green and inexpensive generation of skeletal diversity in the construction of natural product-like libraries. With this in mind, we have developed a diversity-oriented strategy, whereby the parent triterpenoids bryonolic acid and lanosterol are converted to the pseudo-symmetrical polyketones by sequential allylic oxidation and oxidative cleavage of the bridging double bond at the B/C-ring fusion. The resultant polyketones were hypothesized to undergo divergent Norrish-Yang cyclization to produce unique 6/4/8-fused triterpenoid analogs. The subtle differences between parent triterpenoids led to dramatically different spatial arrangements of reactive functionalities. This finding was rationalized through conformational analysis to explain unanticipated photoinduced pinacolization, as well as the regio- and stereochemical outcome of the desired Norrish-Yang cyclization.
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