Highly Efficient Syntheses of Hyaluronic Acid Oligosaccharides

Abstract

Highly efficient syntheses of hyaluronic acid oligosaccharides have been accomplished through the pre-activation based iterative one-pot strategy. A series of oligosaccharides ranging from di-to hexasaccharides were rapidly assembled using only near stoichiometric amounts of the building blocks without aglycon adjustment or purifications of intermediate oligosaccharides. Deprotection and oxidation protocols were developed for protective group removal and oxidation-state adjustment. The availability of such structurally well defined synthetic hyaluronic acid oligosaccharides will greatly facilitate the establishment of detailed structure-function relationships.

Divergent Heparin Oligosaccharide Synthesis with Preinstalled Sulfate Esters

“…[29,32] To access diverse heparin oligosaccharide structures by a divergent route, we designed an advanced disaccharide 1 to serve as a key intermediate, which can be readily transformed into multiple building blocks (Scheme 1a). Disaccharide 1 was formed stereospecifically through the treatment of glucoside 6 [38] with the azide bearing glucosamine donor 5 [9] promoted by p Tol-SOTf, [39] which was formed in situ through the reaction of p TolSCl with AgOTf. The newly formed α linkage was confirmed by NMR analysis ( 3 J H1′,H2′ = 4.2 Hz, 1 J C1′,H1′ = 173.9 Hz).…”

Chemical synthesis of the pentasaccharide related to the repeating unit of the O-antigen of Enterobacter cloacae G2277

“…The known galactose derivative 2 5 was treated with p-anisaldehydedimethylacetal in the presence of 10-camphorsulfonic acid (CSA) 6 to afford the 4,6-O-(4-methoxy benzylidene) derivative 3 in 89% yield. The remaining hydroxyl groups were further benzylated using BnBr in the presence of NaH 7 to give the fully protected derivative 4 in 94% yield.…”

“…½a 25 D þ 74 (c 0.9, CHCl 3 ); Rf (n-hexaneEtOAc, 3:1) 0. 35 6.93, 6.82 (2d, 4H, J 9.0 Hz, C 6 H 4 OCH 3 ), 5.49 (dd, 1H, J 1 00 ,2 00 1. 5 Hz, J 2 00 ,3 00 3.5 Hz H-2 00 ), 5.38 (dd, 1H, J 2 00 ,3 00 3.…”

Obstacles and solutions for chemical synthesis of syndecan-3 (53–62) glycopeptides with two heparan sulfate chains

“…Although uronic acid thioglycosyl and trichloroacetimidate donors have been successfully utilized in glycosaminoglycan synthesis, 92–93 in our experience, the corresponding hexose donors tend to give higher glycosylation yields. 94 Thus, idose and glucose building blocks were used for constructing the glycosyl linkages, which would be followed by oxidation to uronic acids. 95 The synthesis started from the preparation of the non-reducing end AB disaccharide by reacting donor 5 with acceptor 6 .…”