Dataset Information

An Oxidative Dearomatization Approach To Prepare the Pentacyclic Core of Ryanodol.

ABSTRACT: An approach to synthesize the pentacyclic framework of the polyol diterpenoid ryanodol is reported. The ABC tricycle was constructed by a Co-mediated Pauson-Khand reaction, and both radical and anionic cyclization pathways were developed to form the E-ring. In addition, a reaction sequence involving SeO2-mediated enone oxidation and hydroxyl-directed oxy-Michael addition was developed to introduce the A-ring oxidation. The feasibility of forming the bridging D-ring by an oxidative dearomatization was established.

SUBMITTER: Xu C

PROVIDER: S-EPMC6103443 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

An Oxidative Dearomatization Approach To Prepare the Pentacyclic Core of Ryanodol.

Xu Chen C Han Arthur A Reisman Sarah E SE

Organic letters 20180613 13

An approach to synthesize the pentacyclic framework of the polyol diterpenoid ryanodol is reported. The ABC tricycle was constructed by a Co-mediated Pauson-Khand reaction, and both radical and anionic cyclization pathways were developed to form the E-ring. In addition, a reaction sequence involving SeO<sub>2</sub>-mediated enone oxidation and hydroxyl-directed oxy-Michael addition was developed to introduce the A-ring oxidation. The feasibility of forming the bridging D-ring by an oxidative dea ...[more]

PMID: 29897247

Similar Datasets

Project description:Biocatalytic reactions embody many features of ideal chemical transformations, including the potential for impeccable selectivity, high catalytic efficiency, mild reaction conditions and the use of environmentally benign reagents. These advantages have created a demand for biocatalysts that expand the portfolio of complexity-generating reactions available to synthetic chemists. However, the tradeoff that often exists between the substrate scope of a biocatalyst and its selectivity limits the application of enzymes in synthesis. We recently demonstrated that a flavin-dependent monooxygenase, TropB, maintains high levels of site- and stereoselectivity across a range of structurally diverse substrates. Herein, we disclose the structural basis for substrate binding in TropB, which performs a synthetically challenging asymmetric oxidative dearomatization reaction with exquisite site- and stereoselectivity across a range of phenol substrates, providing a foundation for future protein engineering and reaction development efforts. Our hypothesis for substrate binding is informed by a crystal structure of TropB and molecular dynamics simulations with the corresponding computational TropB model and is supported by experimental data. In contrast to canonical class A FAD-dependent monooxygenases in which substrates bind in a protonated form, our data indicate that the phenolate form of the substrate binds in the active site. Furthermore, the substrate position is controlled through twopoint binding of the phenolate oxygen to Arg206 and Tyr239, which are shown to have distinct and essential roles in catalysis. Arg206 is involved in the reduction of the flavin cofactor, suggesting a role in flavin dynamics. Further, QM/MM simulations reveal the interactions that govern the facial selectivity that leads to a highly enantioselective transformation. Thus, the structural origins of the high levels of site-and stereoselectivity observed in reactions of TropB across a range of substrates are elucidated, providing a foundation for future protein engineering and reaction development efforts.

Dataset Information

An Oxidative Dearomatization Approach To Prepare the Pentacyclic Core of Ryanodol.

Publications

An Oxidative Dearomatization Approach To Prepare the Pentacyclic Core of Ryanodol.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets