FR177391, A New Anti-hyperlipidemic Agent from Serratia

Abstract

FR177391 produced by Serratia liquefaciensNo. 1821 enhances differentiation of mouse 3T3-L1 fibroblasts to adipocytes and reduces the circulating levels of triglyceride in C57BL/KsJ-db/bd mice, an obese noninsulin-dependent diabetes mellitus animal model, although its mechanism of actions remained to be unknown. Its active derivative, 20-hydroxy FR177391, and its inactive derivative, 3-hydroxy FR177391 were produced by microbial conversion of FR177391, and biotin-labeled FR177391 was synthesized from 20-hydroxy FR177391 as an active affinity ligand to identify target molecules of FR177391 by chemical genetic approaches.

Biosynthesis of polyketides by trans-AT polyketide synthases

“…An affinity chromatography approach was utilized to elucidate the molecular interaction partner of 153 via a biotinylated analog. 389,390 Although several total synthetic routes towards haterumalides were described (reviewed elsewhere 391 ), the most efficient route yields only 1.3% of 153. 392,393 Therefore, for the generation of the biotinylated 20-hydroxyoocydin A, 153 was bioconverted into 20-hydroxy-oocydin A by Amycolatopsis azurea, followed by chemical introduction of the biotin affinity tag.…”

Marine cytotoxic macrolides haterumalides and biselides, and related natural products

“…This compound is the enantiomer of haterumalide NA ( 1 ). They reported on a detailed study of its anti‐hyperlipidemic activity10 and the microbial conversion into 20‐hydroxy FR177391 ( 14 ) 11. In addition, they identified its molecular target as protein phosphatase 2A 12…”

Second-Generation Total Synthesis of Haterumalide NA Using B-Alkyl Suzuki–Miyaura Coupling

“…Nozaki–Hiyama–Kishi coupling with 2,4-dimethoxybenzyl 33 afforded the coupling product 35 . The 2,4-dimethoxybenzyl ester in 35 was cleaved with TFA and anisole to afford haterumalide NA ( 1 ) . Synthetic haterumalide NA ( 1 ) gave spectral data ( 1 H NMR, 13 C NMR, HRMS, and CD) in full agreement with those of the natural one, 1 completing the total synthesis.…”