The dehydration of N-acetylglucosamine (GlcNAc) to enantiopure dihydroxyethyl acetamidofuran (Di-HAF)

Abstract

A scalable synthesis of enantiopure dihydroxyethyl acetamidofuran (Di-HAF) from N-acetylglucosamine (GlcNAc) and valuable insights into the mechanism of the subsequent acid catalysed conjugated dehydration to 3-acetamido-5-acetylfuran (3A5AF).

Haber-independent, asymmetric synthesis of the marine alkaloid epi-leptosphaerin from a chitin-derived chiral pool synthon

“…The NMR spectroscopic data for synthetic epi-leptosphaerin was in full agreement with the natural product. 30 However, the optical rotation for our synthetic sample [[α] 22 D −32.9 (c 0.07, H 2 O)] differed significantly to the literature value [[α] 25 D +6.5 (c 0.07, H 2 O)]. 30 We have been unable to establish contact with the authors of the isolation report to discuss this discrepancy, but we are confident in our absolute stereochemical assignment; our synthesis began with natural N-acetyl-D-glucosamine and epi-leptopshaerin crystallised and a chiral structure in the Sohncke space group P2 1 2 1 2 1 ; only one enantiomer can be found in the asymmetric unit, thus confirming the absolute stereochemistry as 4R, 5R (Fig.…”

“…workers reported a higher yielding procedure using more favourable reaction conditions. 25 Importantly, both procedures deliver Di-HAF in high enantiomeric excess. Herein, we showcase the first application of Di-HAF as a chiral pool synthon, namely in the Haber-free synthesis of the natural product epi-leptosphaerin, [26][27][28][29][30][31] which also affirms the structure of this marine alkaloid that bears a striking structural resemblance to ascorbic acid (vitamin C) (Scheme 3).…”

“…During the course of our study, Minnaard and co-workers reported a higher yielding procedure using more favourable reaction conditions. 25 Importantly, both procedures deliver Di-HAF in high enantiomeric excess.…”

π-Facial selectivity in the Diels–Alder reaction of glucosamine-based chiral furans and maleimides

“…Prime examples of such heterocycles are the 3-amido-furans derived from N-acetyl glucosamine: dihydroxyethyl acetamidofuran (Di-HAF (1)) and 3-acetamido-5-acetylfuran (3A5AF (2)). Since practical methods for their preparation have become available in the last decade, [3][4][5][6] these building blocks have found several synthetic applications. [7][8][9] The use of furans in the Diels-Alder (DA) cycloaddition is as old as the named reaction itself.…”

“…Recently, our group reported on the synthesis of enantiopure dihydroxyethyl acetamidofuran ( Di-HAF ( 1 )), 3 an unique enantiopure carbohydrate derived furan (Scheme 2). Application of this chiral pool building block is part of our ongoing research and we expected this electron rich diene to be well suited for Diels–Alder reactions.…”