Bioinspired iterative synthesis of polyketides

Abstract

Diverse array of biopolymers and second metabolites (particularly polyketide natural products) has been manufactured in nature through an enzymatic iterative assembly of simple building blocks. Inspired by this strategy, molecules with inherent modularity can be efficiently synthesized by repeated succession of similar reaction sequences. This privileged strategy has been widely adopted in synthetic supramolecular chemistry. Its value also has been reorganized in natural product synthesis. A brief overview of this approach is given with a particular emphasis on the total synthesis of polyol-embedded polyketides, a class of vastly diverse structures and biologically significant natural products. This viewpoint also illustrates the limits of known individual modules in terms of diastereoselectivity and enantioselectivity. More efficient and practical iterative strategies are anticipated to emerge in the future development.

Stereocontrolled Synthesis of Harzialactone A and Its Three Stereoisomers by Use of Standardized Polyketide Building Blocks

“…Mimicking the biosynthetic pathway toward natural polyketides is a challenging but sublime task for synthetic chemists since nature's pure efficacy in forming carbon–carbon bonds and performing stereoselective carbonyl reductions and regioselective dehydratizations is simply unmatched. In the course of time, a multitude of elegant but individual solutions were developed to accomplish the formation of specific molecules with 1,3‐polyols,, utilizing chiral ligands or catalysts, or by starting with enantiomerically pure building blocks (i.e., chiral pool) . General strategies that adopt nature's iterative assembly of simple building blocks in natural product synthesis are less frequent.…”

Enantioselective Total Synthesis of (−)‐Doliculide Using Catalytic Asymmetric Hydrogenations

“…The diastereoisomeric ratio of product was determined after converting to amide with aniline. (4 (12 (13 (14 [(2R,3S,5S)-3-{[tert-Butyl(dimethyl)silyl]oxy}-5-(methoxymethoxy)-2,6-dimethylheptyl]-2,2-dimethyl-1,3-dioxane-4,6-dione (16 (17).…”

“…Over the past decades, tremendous efforts have been made to the syntheses of polyketides because of their various pharmacological activities. [3][4][5] Doliculide is a novel 16membered polyketide isolated from Japanese sea hare Dolabella auricularia. It exhibited potent in vitro antiproliferative activity against the human leukemia cell line HeLa-S3 with an IC 50 value of 1 ng/mL.…”

Structurally Diverse Polyketides From the Mangrove-Derived Fungus Diaporthe sp. SCSIO 41011 With Their Anti-influenza A Virus Activities

“…Polyketides represent an important category of secondary metabolites with great structural diversity from simple aromatics to highly modified complex architectures, such as macrolides, polyphenols, polyethers, polyenes, and enediynes (Fujii, 2010 ; Zheng et al, 2015 ). Distributing broadly in microbial origins, they are constructed by combination of iterative polyketide synthases (PKSs) and multifunctional and iterative oxygenases (Hang et al, 2016 ).…”