A Facile Method for Oxidation of Primary Alcohols to Carboxylic Acids and Its Application in Glycosaminoglycan Syntheses

Abstract

A convenient two-step, one-pot procedure was developed for the conversion of primary alcohols to carboxylic acids. The alcohol was first treated with NaOCl and TEMPO under phase-transfer conditions, followed by NaClO 2 oxidation in one pot. This reaction is applicable to a wide range of alcohols and the mild reaction conditions are compatible with many sensitive functional groups, including electron-rich aromatic rings, acid-labile isopropylidene ketal and glycosidic linkages, and oxidation-prone thioacetal, p-methoxybenzyl, and allyl moieties. Several glycosaminoglycans such as heparin, chondroitin, and hyaluronic acid oligosaccharides have been synthesized in high yields by using this new oxidation protocol.

Synthesis of Monomeric and Dimeric Repeating Units of the Zwitterionic Type 1 Capsular Polysaccharide from Streptococcus pneumoniae

“…Jones oxidation [33] requires strong acidic conditions which are not compatible with sensitive functional groups, such as electron-rich aromatic rings, acid labile isopropylidene ketals and glycosidic linkages, and precludes its application for the synthesis of complex oligosaccharides. Recently, Huang [34] and co-workers developed a novel two-step, one-pot procedure for the conversion of primary alcohols to carboxylic acids under very mild conditions in good yields. Using a similar procedure employing sodium hypochlorite and 2,2,6,6-tetramethylpiperidine-oxyl (TEMPO), the two hydroxymethyl groups after selective deacetylation of trisaccharide 17 were concurrently oxidized to the corresponding uronic acids, which were protected as benzyl ethers [12,35] for ease of purification to give the trisaccharide 18.…”

“…[10][11][12][13] The alternative strategy adopted here is to create uronic acid units by oxidation of the hydroxymethyl group of appropriately prepared substrate oligosaccharides. [11][12]34] Implementation of this approach requires the stereoselective construction of a1,3 and a1,4 galactopyranosyl linkages. Typically these require glycosyl donors possessing a non-participating functionality at the C2 position, which may lead to anomeric mixtures.…”

Highly Efficient Syntheses of Hyaluronic Acid Oligosaccharides

“…In contrast to literature results, 2,2,6,6-tetramethylpiperidinyl-1-oxy (TEMPO)/NaOCl [21,[49][50][51][52][53][54][55][56] or TEMPO/iodobenzene diacetate [57] oxidation led to a mixture of partially oxidized products, which is probably due to the hydrophobic nature of our fully protected oligosaccharides. [58] A two-step process of Dess-Martin oxidation and subsequent treatment with NaClO 2 [59] also gave inconsistent results. Through extensive experimentation, we discovered that with a twostep one-pot oxidation protocol of NaOCl/TEMPO followed by addition of NaClO 2 , [58] we were able to carry out this transformation cleanly, which was followed by benzyl ester formation with phenyl diazomethane producing ester 37.…”

“…[58] A two-step process of Dess-Martin oxidation and subsequent treatment with NaClO 2 [59] also gave inconsistent results. Through extensive experimentation, we discovered that with a twostep one-pot oxidation protocol of NaOCl/TEMPO followed by addition of NaClO 2 , [58] we were able to carry out this transformation cleanly, which was followed by benzyl ester formation with phenyl diazomethane producing ester 37. [60] Removal of TBS, catalytic hydrogenation, transamidation with methyl amine and selective acetylation led to fully deprotected sHA hexasaccharide 38 in 44% overall yield from 36 (Scheme 3b).…”

Modular Strategies for Structure and Function Employed by Marine Cyanobacteria: Characterization and Synthesis of Pitinoic Acids

“…Additionally, two-step oxidation protocols to the aldehyde and then to the acid were also inefficient to produce the desired carboxylic acid, including Dess-Martin oxidation followed by NaClO 2 or PDC treatment, and TEMPO-catalyzed oxidations with NaOCl/NaClO 2 system. 15 Notably, the aldehyde could be obtained in some trials, but not the desired acid. Also, the exo-methylene group in the fatty acid part appeared to be affected by the NaOCl/NaClO 2 oxidizing system, as the corresponding peaks for those olefinic protons disappeared in the 1 H NMR spectrum.…”