Total Synthesis and Structure Revision of a Fungal Glycolipid Fusaroside

Abstract

Herein, we report a strategy for the total synthesis of a structurally unique fungal glycolipid fusaroside. The first total synthesis of the proposed structure involved construction of the complex, branched lipid chain having a variety of alkenes with E stereochemistry and attachment of the masked α,β-unsaturated βketo acid at the O-4 position of trehalose as key steps. We propose a revision in the structure of fusaroside, particularly the position of olefins in the lipid chain.

Total Synthesis and Structure Confirmation of Fusaroside

“…Subsequent DMP oxidation of allylic alcohol 16 gave the corresponding β-ketoester derivative (80%) which upon reaction with sodium hydride and methyl iodide at 0 °C delivered compound 17 in an 88% yield. In the final step, all PMB groups were removed using TFA and anisole as a benzyl cation scavenger, , leading to fusaroside 1a in a 72% yield, upon silica gel column chromatographic purification using MeOH/EtOAc (15:85) as the eluent.…”

“…Due to our long-standing interest in the chemical synthesis of trehalose-containing glycolipids and oligosaccharides, − fusaroside 1 attracted our immediate attention and eventually we were successful in synthesizing the molecule . However, the NMR data of our synthesized compound 1 did not match with the data of the isolated fusaroside.…”

“…We then analyzed the 2D NMR data provided in the Supporting Information of the isolation paper (COSY, HSQC, HMBC spectra) and appropriately revised the assignments of the protons and carbons of the lipid chain. This along with the comparison with our data helped us to propose the revised structure 1a , wherein the positions of the double bonds in the acyl chain were changed from C11–C12 to C10–C11 and C13–C14 to C14–C15 . Herein, we report the total synthesis of our proposed revised structure 1a and structure confirmation of fusaroside.…”

Total Synthesis of a Trehalose-Containing Lipooligosaccharide Analogue from Mycobacterium linda

“…Gurjar and co-workers have reported the synthesis of the terminal trisaccharide unit (Glc-Rha-Glc) of tetrasaccharide 1 as a methyl glucoside . Our group has been involved in the chemical synthesis of complex trehalose-containing glycolipids and oligosaccharides, including M. tuberculosis SL-1, SL-3, and Ac 2 SGL analogues …”

Synthetic Studies toward Australifungin

“…Kishi’s aldehyde 10 reacted with a Grignard reagent prepared from 4-bromo-1,1-diethoxybutane 8 and magnesium to afford the secondary alcohol 11 as a diastereomeric mixture (Scheme 2 ). Notably, this diastereomeric mixture displayed only a single set of 1 H NMR signals, presumably due to the long distance between the two chiral centers.…”