Direct Synthesis of Maradolipids and Other Trehalose 6‑Monoesters and 6,6′-Diesters

• Published in: Journal of organic chemistry Vol. 78; no. 2; pp. 363 - 369
• Main Authors: Paul, Nawal K, Twibanire, Jean-d’Amour K, Grindley, T. Bruce
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 18.01.2013; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Esters; Fatty Acids - chemical synthesis; Fatty Acids - chemistry; Glycolipids - chemical synthesis; Glycolipids - chemistry; Magnetic Resonance Spectroscopy; Molecular Structure; Physical Sciences; Pyridines - chemistry; Science & Technology; Trehalose - chemical synthesis; Trehalose - chemistry; Urea - analogs & derivatives; Urea - chemistry; CAENORHABDITIS-ELEGANS; CRYSTAL-STRUCTURE; ESTERS; DIACYLTREHALOSE GLYCOLIPIDS; FATTY-ACIDS; CORD-FACTOR ANALOGS; DAUER LARVA; ALPHA,ALPHA-TREHALOSE; HYDROXYMETHYL GROUP CONFORMATION; SCALE SYNTHESIS
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo302231v

It was shown that reaction of trehalose with 1 equiv of a fatty acid in pyridine promoted by 1 equiv of the uronium-based coupling agent 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) at room temperature gives a good yield of the primary ester accompanied by small amounts of the diprimary ester using hexanoic, palmitic, and oleic acids as examples. Reactions using 2 equiv of the fatty acids gave the symmetrical diesters. The monoesters were reacted with different fatty acids to give nonsymmetric 6,6′-diesters in very good yields. Compounds synthesized include the most abundant component of the very complex maradolipid mixture, 6-O-(13-methyltetradecanoyl)-6′-O-oleoyltrehalose, and a component potentially present in this mixture, 6-O-(12-methyltetradecanoyl)-6′-O-oleoyltrehalose, a derivative of an ante fatty acid. The C5–C6 rotameric populations of 6-O-monoesters, symmetrical 6,6′-diesters, and 2,6,6′-triesters of fatty acids were calculated from the values of the H5–H6R and H5–H6S coupling constants and found to be similar to those found for glucose. The rotameric populations of the monosubstituted glucose residues in the 2,6,6′-triesters was altered considerably to favor the gt rotamer, presumably because of attraction between the 2- and 6′-fatty acid chains.