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

Abstract

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.

The Uptake of Trehalose Glycolipids by Macrophages Is Independent of Mincle

“…These conditions gave the monoester 6 in 41 % yield along with the corresponding diester (19 %) and starting material (30 %), with the products being readily separated by silica gel flash column chromatography. Whereas others have reported slightly improved yields for the monoesterification of 5 and were able to directly esterify 4 when using shorter-chain acids, [25,26] we encountered difficulties in solubilising the longer-chain acid and the formation of the Steglich esterification product [27] despite exploring a variety of reaction conditions. The second esterification reaction was then undertaken with 11-azido-undecanoic acid (8), itself prepared in 91 % yield by treating 11-bromoundecanoic acid (7) with NaN 3 .…”

Tailoring trehalose for biomedical and biotechnological applications

“…Other methods have been developed to directly mono-6- O -acylate unprotected trehalose either chemically or enzymatically, although removing all side products from the target compound is challenging. 109,110 If these purification issues can be addressed, such one-step methods offer a powerful approach to the synthesis of TMM-mimicking probes.…”

Synthesis of novel types of polyester glycodendrimers as potential inhibitors of urinary tract infections

“…In the case of diols, reactions were high yielding with short reaction times as expected based on our previous studies. [54][55][56] As illustrated in Scheme 3, diol 16 reacted for 4 hours to afford the corresponding diazide 17 in 85% yield, while 19 yielded 20 in 94% yield after 2 hours. To obtain a highly mannosylated system, a third generation polyester dendrimer was divergently constructed.…”