Synthesis of the Heparin‐Based Anticoagulant Drug Fondaparinux

Abstract

Fondaparinux, a synthetic pentasaccharide based on the heparin antithrombin-binding domain, is an approved clinical anticoagulant. Although it is a better and safer alternative to pharmaceutical heparins in many cases, its high cost, which results from the difficult and tedious synthesis, is a deterrent for its widespread use. The chemical synthesis of fondaparinux was achieved in an efficient and concise manner from commercially available d-glucosamine, diacetone a-dglucose, and penta-O-acetyl-d-glucose. The method involves suitably functionalized building blocks that are readily accessible and employs shared intermediates and a series of one-pot reactions that considerably reduce the synthetic effort and improve the yield.

Reagent Controlled Glycosylations for the Assembly of Well-Defined Pel Oligosaccharides

“…Thus, DTBS-GalN donors also represent attractive building blocks for Pel assembly. For the stereoselective introduction of α- d -GlcN linkages, no general solution exists, even though the construction of this type of glycosidic linkage has attracted significant attention, 4 , 5 as it is present in many important natural polysaccharides and glycoconjugates such as heparin, heparan sulfate, 6 GPI anchors, and various bacterial polysaccharides. 7 …”

One‐Pot Methods for the Protection and Assembly of Sugars

“…The regioselectivity of the benzyl removal is quite tricky, which gives caution to the outright use of the method. Cases with hydrolysis of the Fmoc group92 and benzylidene acetal,93 right after glycosylation in the same flask, were also demonstrated; however, the resulting reaction solutions were no longer favorable to subsequent glycosylation in the same flask. The use of Fmoc nevertheless enables a convenient sequential iterative process for sugar elongation.…”

Profiling Heparan Sulfate‐Heavy Metal Ions Interaction Using Electrochemical Techniques

“…I tetrasaccharides synthesis relied on the synthesis of tetrasac- Chemistry-A European Journal charide precursor 14 from the disaccharides 12 and 13 via deacetylation, oxidation, lactonization, azide reduction and N-acetylation as was previously described. [7,27] Nap/TBDMS orthogonality was used to access all three I tetrasaccharides from tetrasaccharide 14 via sequential deprotection and sulfation steps (Scheme 2). The removal of TBDPS from 14 afforded the O-6 free tetrasaccharide 15, which following sulfation afforded O-6 sulfated tetrasaccharide 17.…”