Deng Heping, Yang Junhong, Li Fuzhuo, Li Jian, Renata Hans
Department of Chemistry, BioScience Research Collaborative, Rice University, Houston, TX, USA.
Department of Natural Medicine, School of Pharmacy, Fudan University, Shanghai, China.
Nat Chem. 2025 Jun 16. doi: 10.1038/s41557-025-01852-6.
Due to the structural complexity of natural products, their target-oriented syntheses usually require the design of individualized routes that are tailor-made for the specific targets. As such, route redesign is needed when targets of different skeletal connectivities are considered. Here we report a versatile synthetic strategy that runs counter to this conventional wisdom and allows access to a range of terpenoids with distinct skeletal frameworks from the sesquiterpene lactone sclareolide as the starting material. By viewing a biocatalytically installed alcohol as an exploitable motif rather than a structural endpoint, a number of abiotic skeletal rearrangements were designed, resulting in substantial structural divergence from the original drimane ring system of sclareolide. Using this approach, the syntheses of four terpenoid natural products, namely, merosterolic acid B, cochlioquinone B, (+)-daucene and dolasta-1(15),8-diene, were achieved.
由于天然产物的结构复杂性，其靶向合成通常需要设计针对特定目标量身定制的个性化路线。因此，当考虑具有不同骨架连接性的目标时，就需要重新设计路线。在此，我们报道了一种通用的合成策略，该策略与这种传统观念背道而驰，能够以倍半萜内酯香紫苏内酯为起始原料，获得一系列具有不同骨架结构的萜类化合物。通过将生物催化引入的醇视为可利用的基团而非结构终点，设计了许多非生物骨架重排反应，从而使产物结构与香紫苏内酯原有的菖蒲烷环系统产生了显著差异。利用这种方法，实现了四种萜类天然产物的合成，即异甾醇酸B、耳壳藻醌B、(+)-胡萝卜素和多拉司他-1(15),8-二烯。
