Du Biao, Yuan Changchun, Yu Tianzi, Yang Li, Yang Yang, Liu Bo, Qin Song
Key Laboratory of Green Chemistry and Technology of the Ministry of Education Institution, College of Chemistry, Sichuan University, Chengdu, Sichuan 610064 (China), Fax: (+86) 28-8541-3712.
Chemistry. 2014 Feb 24;20(9):2613-22. doi: 10.1002/chem.201304378. Epub 2014 Feb 2.
In this article, we describe our efforts on the total synthesis of bolivianine (1) and isobolivianine (2), involving the synthesis of onoseriolide (3). The first generation synthesis of bolivianine was completed in 21 steps by following a chiral resolution strategy. Based on the potential biogenetic relationship between bolivianine (1), onoseriolide (3), and β-(E)-ocimene (8), the second generation synthesis of bolivianine was biomimetically achieved from commercially available (+)-verbenone in 14 steps. The improved total synthesis features an unprecedented palladium-catalyzed intramolecular cyclopropanation through an allylic metal carbene, for the construction of the ABC tricyclic system, and a Diels-Alder/intramolecular hetero-Diels-Alder (DA/IMHDA) cascade for installation of the EFG tricyclic skeleton with the correct stereochemistry. Transformation from bolivianine to isobolivianine was facilitated in the presence of acid. The biosynthetic mechanism and the excellent regio- and endo selectivities in the cascade are well supported by theoretical chemistry based on the DFT calculations.
在本文中，我们描述了我们在玻利维亚宁（1）和异玻利维亚宁（2）全合成方面所做的工作，其中涉及onoseriolide（3）的合成。玻利维亚宁的第一代合成通过手性拆分策略以21步完成。基于玻利维亚宁（1）、onoseriolide（3）和β-(E)-罗勒烯（8）之间潜在的生源关系，玻利维亚宁的第二代合成以市售的(+)-马鞭草烯酮为原料，通过仿生合成在14步内实现。改进后的全合成具有前所未有的钯催化分子内环丙烷化反应，通过烯丙基金属卡宾构建ABC三环体系，以及狄尔斯-阿尔德/分子内杂狄尔斯-阿尔德（DA/IMHDA）串联反应，用于以正确的立体化学安装EFG三环骨架。在酸的存在下，玻利维亚宁向异玻利维亚宁的转化得以促进。基于密度泛函理论（DFT）计算的理论化学很好地支持了串联反应中的生物合成机制以及出色的区域选择性和内型选择性。
