Synthesis of disaccharide fragments of the AT-III binding domain of heparin and their sulfonatomethyl analogues

Abstract

d-Glucuronate and l-iduronate-containing disaccharides related to the antithrombin-binding domain of heparin were prepared. The carboxylic function of the uronic acid unit was formed on a disaccharide level in the case of the glucuronate, while on a monosaccharide level in the case of the iduronate derivatives. Synthesis of their sulfonic acid analogues was carried out analoguosly applying sulfonatomethyl-containing acceptors in the form of either salts or methyl esters. Significant difference could be observed in the methyl ether formation reactions of the sulfonatomethyl-containing uronate disaccharides and the non-sulfonic acid uronates.

AuCl3– and AuCl3–Phenylacetylene‐Catalyzed Glycosylations by Using Glycosyl Trichloroacetimidates

“…Table 1. Reactions were performed by using AuCl 3 Similar trends were observed when sugar-derived alcohols 7 and 8 were employed in the glycosylation to obtain 14 [21] and 15, [22] respectively (Table 1, Entries 4 and 5). [a] [a] Room temperature was 35-39°C.…”

“…[18] Amino acid derived nucleophiles were synthesized according to literature procedures. [10,11,16,[20][21][22][23][24] Analytical data for glycosides 16 and 17 are given below. The reaction was allowed to continue at room temperature until the starting material was consumed (monitored by TLC analysis).…”

“…The crude products were then purified by silica gel column chromatography (hexane and ethyl acetate) to afford glycosides 11 ( 11-15, 19-24, and 27-31 were in agreement with data from the literature. [10,11,16,[20][21][22][23][24] Analytical data for glycosides 16 and 17 are given below. N-(9-Fluorenylmethyloxycarbonyl)-O-(2,3,4,6-tetra-O-acetyl-D…”

Synthesis of C‐2‐ and C‐3‐Sulfonatomethyl O‐ and S‐Glycosides by Horner–Wadsworth–Emmons Olefination

“…The isosteric sulfonic acid analogues of carbohydrate sulfates are enzymatically stable compounds that can be used as tools to better understand these biological functions or to develop leads for new anticoagulant, antitumour and antimicrobial agents. Accordingly, various approaches have been developed for producing sulfonic acid analogues of the sulfated Lewis X trisaccharide, glucose 6‐sulfate, sulfated glycolipids, and heparin . Moreover, carbohydrate sulfonates are of interest as bioisosters of phosphates and carboxylates such as nucleotides, mannose‐6‐phosphate, and sialic acid derivatives …”

“…[12][13][14][15] Some years ago we initiated a research project to prepare isosteric sulfonic acid analogues of the antithrombin binding pentasaccharide domain of heparin to access new anticoagulants. [6,[16][17][18][19][20][21][22] Recently, we demonstrated that the blood clotting inhibitory activity of the parent highly sulfated pentasaccharide could be improved by the replacement of the primary sulfate esters with a sodium sulfonatomethyl group. [19] Continuing on from this, we targeted the synthesis of further pentasaccharide analogues bearing the sulfonic acid moiety at secondary positions by using thioglycoside building blocks bearing a dynamics and DFT calculations.…”