334834-19-4Relevant academic research and scientific papers
Synthesis of Fondaparinux: Modular synthesis investigation for heparin synthesis
Lin, Feng,Lian, Gaoyan,Zhou, Ying
, p. 32 - 39 (2013)
The anti-thromboembolic pentasaccharide Fondaparinux was synthesized in 36 steps for the longest linear route, with 0.017% overall yield from d-glucose. Only three kinds of protecting groups were used for hydroxyl protection, Bn, Ac, and Bz, to accomplish this complex synthesis without decreasing the synthetic efficiency. Three l-idopyranosyl donors were investigated. Thioethyl glycoside is an efficient donor for l-idopyranosyl glycosylation with full α-selectivity, while l-idopyranosyl trichloroacetimidate resulted in poor α/β selectivity. A practical synthesis of key intermediate 1,6-anhydro-l-idopyranose 17 by H+/β-CD catalyst was developed.
Glycosylations of Simple Acceptors with 2-O-Acyl l-Idose or l-Iduronic Acid Donors Reveal Only a Minor Role for Neighbouring-Group Participation
Mohamed, Shifaza,He, Qi Qi,Lepage, Romain J.,Krenske, Elizabeth H.,Ferro, Vito
, p. 2214 - 2227 (2018/06/04)
Several l-idose and l-iduronic acid glycosyl donors (mostly thioglycosides but also halides and trichloroacetimidates) with acyl protecting groups at the C-2 position were prepared and evaluated in glycosylation reactions with simple acceptors. In glycosaminoglycan oligosaccharide syntheses in the literature, the presence of C-2 acyl protecting groups in l-ido-configured glycosyl donors generally results in exclusive formation of 1,2-trans glycosidic linkages, a finding that has typically been attributed to neighbouring-group participation. However, glycosylations of simple alcohols with l-ido-configured donors (particularly thioglycosides), reported here, generally displayed incomplete stereocontrol and gave mixtures of the 1,2-trans and 1,2-cis products, suggesting that neighbouring-group participation has lesser importance in these reactions. Glycosyl donors and reaction conditions were identified that gave improved, but not exclusive, selectivity for the desired α-l-anomer (1,2-trans) as the major product. Interestingly, glycosylations under the same reaction conditions with more complex monosaccharide acceptors gave exclusively the expected 1,2-trans products. The role of neighbouring-group participation in these glycosylations was explored with density functional theory (DFT) calculations, which revealed that the non-stereoselective addition of the acceptor alcohol to the intermediate oxocarbenium ion is competitive with the stereospecific addition of the acceptor to the acyloxonium ion intermediate.
METHODS AND INTERMEDIATES FOR THE PREPARATION OF FONDAPARINUX
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, (2014/01/08)
The present invention relates to methods for the synthesis of fondaparinux and intermediates thereto.
Synthesis of heparin oligosaccharides and their interaction with eosinophil-derived neurotoxin
Hung, Shang-Cheng,Lu, Xin-An,Lee, Jinq-Chyi,Chang, Margaret Dah-Tsyr,Fang, Shun-Lung,Fan, Tan-Chi,Zulueta, Medel Manuel L.,Zhong, Yong-Qing
, p. 760 - 772 (2012/02/05)
A convenient route for the synthesis of heparin oligosaccharides involving regioselective protection of d-glucosamine and a concise preparation of rare l-ido sugars from diacetone α-d-glucose is described. Stereoselective coupling of a d-glucosamine-derived trichloroacetimidate with a 1,6-anhydro-β-l-idopyranosyl 4-alcohol gave the desired α-linked disaccharide, which was used as repeating unit for dual chain elongation and termination. Stepwise assembly from the reducing to the non-reducing end with a d-glucosamine-derived monosaccharide as starting unit furnished the oligosaccharide skeletons having different chain lengths. A series of functional group transformations afforded the expected heparin oligosaccharides with 3, 5 and 7 sugar units. Interaction of these oligosaccharides with eosinophil-derived neurotoxin (EDN), a cationic ribonuclease and a mediator produced by human eosinophils, was further investigated. The results revealed that at 5 μg mL-1, the heptasaccharide has sufficiently strong interference to block EDN binding to Beas-2B cells. The tri- and pentasaccharides have moderate inhibitory properties at 50 μg mL-1 concentration, but no inhibition has been observed at 10 μg mL-1. The IC50 values of the tri-, penta- and heptasaccharides are 69.4, 47.2 and 0.225 μg mL-1, respectively.
Synthesis of 48 disaccharide building blocks for the assembly of a heparin and heparan sulfate oligosaccharide library
Lu, Ng-Dai,Shie, Chi-Rung,Kulkarni, Suvarn S.,Pan, Guan-Rong,Lu, Xin-An,Hung, Shang-Cheng
, p. 5995 - 5998 (2007/10/03)
(Chemical Equation Presented) An efficient synthesis of the entire set of suitably protected 48 disaccharide building blocks for the assembly of a heparin and heparan sulfate oligosaccharide library is described here.
Synthesis of Heparin Oligosaccharides
Lee, Jinq-Chyi,Lu, Xin-An,Kulkarni, Suvarn S.,Wen, Yuh-Sheng,Hung, Shang-Cheng
, p. 476 - 477 (2007/10/03)
An efficient preparation of rare 2-O-benzoyl-3-O-benzyl-1,6-anhydro-β-l-idopyranose from commercially available diacetone α-d-glucose in five straightforward steps is described here. With this key building block in hand, the total syntheses of heparin oligosaccharides with three, five, seven, and nine sugar units are successfully carried out. Copyright
Biologically potent L-hexoses and 6-deoxy-L-hexoses: Their syntheses and applications
Kulkarni, Suvarn S.,Chi, Fa-Chen,Hung, Shang-Cheng
, p. 1193 - 1200 (2007/10/03)
This account describes our recent work in the development of new methodologies to prepare rare and biologically potent L-hexoses and 6-deoxy-L-hexoses, from cheapest D-glucose, via L-hexofuranoses and 1,6-anhydro-β-L-hexopyranoses as key building blocks. Their applications in the syntheses of heparin oligosaccharides, the carbohydrate moiety of bleomycin A2, and L-acovenose are also summarized here.
From D-Glucose to Biologically Potent L-Hexose Derivatives: Synthesis of α-L-Iduronidase Fluorogenic Detector and the Disaccharide Moieties of Bleomycin A2 and Heparan Sulfate
Lee, Jinq-Chyi,Chang, Shu-Wen,Liao, Chih-Cheng,Chi, Fa-Chen,Chen, Chien-Sheng,Wen, Yuh-Sheng,Wang, Cheng-Chung,Kulkarni, Suvarn S.,Puranik, Ramachandra,Liu, Yi-Hung,Hung, Shang-Cheng
, p. 399 - 415 (2007/10/03)
A novel and convenient route for the synthesis of biologically potent and rare L-hexose derivatives from D-glucose is described. Conversion of diacetone-α-D-glucose (14) into 1,2:3,5-di-O-isopropylidene-β -L-idofuranose (19) was efficiently carried out in two steps. Orthogonal isopropylidene rearrangement of compound 19 led to 1,2:5,6-di-O-isopropylidene-β-L-idofuranose (27), which underwent regioselective epimerization at the C3 position to give the L-talo- and 3-functionalized L-idofuranosyl derivatives. Hydrolysis of compound 19 under acidic conditions furnished 1,6-anhydro-β-L-idopyranose (35) in excellent yield, which was successfully transformed into the corresponding L-allo, L-altro, L-gulo, and L-ido derivatives via regioselective benzylation, benzoylation, triflation and nucleophilic substitution as the key steps. Applications of these 1,6-anhydro-β-L-hexopyranoses as valuable building blocks to the syntheses of 4-methylcoumarin-7-yl-α-L-iduronic acid and the disaccharide moieties of bleomycin A2 as well as heparan sulfate are highlighted.
