Two‐Step Preparation of Diverse 3‐Amidofurans from Chitin

Abstract

The synthesis of 3‐amidofurans is laborious due to the difficulty installing a nitrogen substituent at the C3 position of the furan heterocycle. 3‐Acetamido‐5‐acetylfuran (3A5AF), readily available from chitin, is a versatile biorenewable platform that can be converted into a range of functionally rich 3‐amidofurans, streamlining access to this underexplored heteroaromatic chemical space.

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

“…Because of incomplete conversion after 90 minutes, only low yields were found with no acid-or weak acid catalysts (Table 1, entries 1-3). With stronger acids (entries 4-7) the starting material was completely consumed and the phenylboronate ester of Di-HAF (11) was formed in good to excellent yield (73%-95%). We were slightly surprised to find a correlation between acid strength and reaction rate because in pyridine, dissociation of an acid is expected, so the pyridinium ion would be the protonating species in each case.…”

“…While the preparation and use of the two furan derivatives 5-HMF and 3A5AF has been studied actively in recent years, 8,[10][11][12][13][14] the furanyl diol dihydroxyethyl acetamidofuran (Di-HAF) attracted less attention. This bis-dehydration product of GlcNAc was identified by Kuhn and Krüger in 1956 15 as an intermediate in the Morgan-Elson method for quantitative determination of hexosamines 16 and was named chromogen III.…”

Facile Preparation of 3‐Acetamido‐5‐acetylfuran from N‐Acetyl‐d‐glucosamine by using Commercially Available Aluminum Salts

“…3A5AF has the potential to become an important building block for N‐containing aromatic chemicals, and examples of its utilization are present in the literature . This compound was first obtained as a byproduct in a low yield in the pyrolysis of chitin .…”

“…3A5AF has the potentialt ob ecome an important building block for N-containinga romatic chemicals, and examples of its utilization are present in the literature. [9][10][11][12][13] This compound was first obtained as ab yproduct in al ow yield in the pyrolysis of chitin. [14][15][16] Recently,l iquid-phase reactions to synthesize 3A5AFf rom NAG have been proposed.H owever,t he production of 3A5AF has been proven to be ac hallengingr eaction, and often non-conventional methods or harsh conditions are employed.…”

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

“…12 Over the past few years, several reports describing the valorisation of chitin (or its monomer, NAG) into N-platforms have appeared, [13][14][15][16][17] one of the most interesting being 3-acetamido-5-acetylfuran (3A5AF). 18 We have showcased the utility of 3A5AF in the synthesis of several N-scaffolds in a Haber-independent manner (Scheme 1), including the natural product proximicin A, 19 3-azafurans 1 20,21 and novel heteroaromatic scaffolds 2. 22 This research was extended to non-furanic structures by exploring the skeletal rearrangement chemistry of the 3A5AF-derived furfuryl alcohol (±)-3; Piancatelli rearrangement gave the aminocyclopentenone (±)-4, from which a diverse range of N-heterocycles including indoles, pyridines and quinolines were obtained.…”