Rieske oxygenases (ROs) from natural product biosynthetic pathways are a poorly studied group of enzymes with significant potential as oxidative functionalization biocatalysts. A study on the ROs JerL, JerP, and AmbP from the biosynthetic pathways of jerangolid A and ambruticin VS-3 is described. Their activity was successfully reconstituted using whole-cell bioconversion systems coexpressing the ROs and their respective natural flavin-dependent reductase (FDR) partners. Feeding authentic biosynthetic intermediates and synthetic surrogates to these strains confirmed the involvement of the ROs in hydroxymethylpyrone and dihydropyran formation and revealed crucial information about the RO's substrate specificity. The pronounced dependence of JerL and JerP on the presence of a methylenolether allowed the precise temporal assignment of RO catalysis to the ultimate steps of jerangolid biosynthesis. JerP and AmbP stand out among the biosynthetic ROs studied so far for their ability to catalyze clean tetrahydropyran desaturation without further functionalizing the formed electron-rich double bonds. This work highlights the remarkable ability of ROs to highly selectively oxidize complex molecular scaffolds.

2023-05-26·Molecules (Basel, Switzerland)

The Corey-Seebach Reagent in the 21st Century: A Review.

Review

作者: Irfan, Muhammad ; Kotwica-Mojzych, Katarzyna ; Mushtaq, Aqsa ; Ahmad, Sajjad ; Zahoor, Ameer Fawad ; Mojzych, Mariusz ; Mansha, Asim ; Haroon, Muhammad ; Akhtar, Rabia ; Irfan, Ali

The Corey-Seebach reagent plays an important role in organic synthesis because of its broad synthetic applications. The Corey-Seebach reagent is formed by the reaction of an aldehyde or a ketone with 1,3-propane-dithiol under acidic conditions, followed by deprotonation with n-butyllithium. A large variety of natural products (alkaloids, terpenoids, and polyketides) can be accessed successfully by utilizing this reagent. This review article focuses on the recent contributions (post-2006) of the Corey-Seebach reagent towards the total synthesis of natural products such as alkaloids (lycoplanine A, diterpenoid alkaloids, etc.), terpenoids (bisnorditerpene, totarol, etc.), polyketide (ambruticin J, biakamides, etc.), and heterocycles such as rodocaine and substituted pyridines, as well and their applications towards important organic synthesis.

2021-08-02·Chemistry (Weinheim an der Bergstrasse, Germany)2区 · 化学

Enantioselective Total Synthesis of the Putative Biosynthetic Intermediate Ambruticin J

2区 · 化学

Article

作者: Nalin, Ansel ; Taylor, Richard E. ; Chang, Chia‐Fu ; Trentadue, Kathryn

Abstract:

The family of anti‐fungal natural products known as the ambruticins are structurally distinguished by a pair of pyran rings adorning a divinylcyclopropane core. Previous characterization of their biosynthesis, including the expression of a genetically modified producing organism, revealed that the polyketide synthase pathway proceeds via a diol intermediate, known as ambruticin J. Herein, we report the first enantioselective total synthesis of the putative PKS product, ambruticin J, according to a triply convergent synthetic route featuring a Suzuki‐Miyaura cross‐coupling and a Julia‐Kocienski olefination for fragment assembly. This synthesis takes advantage of synthetic methodology previously developed by our laboratory for the stereoselective generation of the trisubstituted cyclopropyl linchpin.

100 项与 KOS-2079 相关的药物交易

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