Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Published: August 2016
AI Article Synopsis
Article Abstract
Sesterterpenoids are a group of terpenoid natural products that are primarily biosynthesized via cyclization of the C25 linear substrate geranylfarnesyl pyrophosphate (GFPP). Although the long carbon chain of GFPP in theory allows for many different cyclization patterns, sesterterpenoids are relatively rare species among terpenoids, suggesting that many intriguing sesterterpenoid scaffolds have been overlooked. Meanwhile, the recent identification of the first sesterterpene synthase has allowed the discovery of new sesterterpenoids by the genome mining approach. In this study, we characterized the unusual fungal sesterterpene synthase EvQS and successfully obtained the sesterterpene quiannulatene (1) with a novel and unique highly congested carbon skeleton, which is further oxidized to quiannulatic acid (2) by the cytochrome P450 Qnn-P450. A mechanistic study of its cyclization from GFPP indicated that the biosynthesis employs an unprecedented cyclization mode, which involves three rounds of hydride shifts and two successive C-C bond migrations to construct the 5-6-5-5-5 fused ring system of 1.
A dual photoredox/cobalt-catalyzed protocol for chemo-, regio-, diastereo- and enantioselective reductive coupling of 1,1-disubstituted allenes and cyclobutenes through chemo-, regio-, diastereo- and enantioselective oxidative cyclization followed by stereoselective protonation promoted by a chiral phosphine-cobalt complex is presented. Such process represents an unprecedented reaction pathway for cobalt catalysis that enables selective transformation of the less sterically congested alkenes of 1,1-disubstituted allenes with cyclobutenes, incorporating a broad scope of tetrasubstituted alkenes into the cyclobutane scaffolds in up to 86% yield, >98:2 chemo- and regioselectivity, >98:2 dr and >99.5:0.
We herein report a switchable coupling of acrylic acids with ethyl glyoxylate under ruthenium catalysis enabling the synthesis of diverse functionalized γ-butenolides. The carboxyl-directed vinylic C-H cleavage and dual nucleophilic addition to aldehyde are achieved to deliver hydroxymethylated butanolides under mild and oxidant-free conditions. Alternatively, a controlled and unprecedented tandem C-H cyclization/oxidative homocoupling reaction is realized by using silver salt as the oxidant to generate a range of dimeric butenolides bearing vicinal all-carbon quaternary centers.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, and Chemical Biology Center, Peking University, 38 Xueyuan Road, Beijing 100191, China.
The text discusses the challenges in total synthesis of natural products, focusing on improving efficiency and allowing for diverse syntheses.
It highlights the use of bioinspired synthesis, especially late-stage skeletal diversification, as an effective strategy to achieve these goals.
The authors summarize their research efforts, including key methods that mimic natural biosynthetic reactions to create complex molecules efficiently, showcasing successful syntheses of various natural products.
