72174-24-4Relevant academic research and scientific papers
Glucose-based spiro-oxathiazoles as: In vivo anti-hyperglycemic agents through glycogen phosphorylase inhibition
Azay-Milhau, Jacqueline,Balzarin, Sophie,Czifrák, Katalin,Demontrond, Fanny,Docsa, Tibor,Duret, Cédric,Gergely, Pál,Goyard, David,Kónya, Bálint,Larini, Paolo,Leroy, Jérémy,Maurel, Patrick,Petit, Pierre,Praly, Jean-Pierre,Somsák, László,Tournier, Michel,Tousch, Didier,Vidal, Sébastien
supporting information, p. 931 - 940 (2020/02/15)
The design of glycogen phosphorylase (GP) inhibitors targeting the catalytic site of the enzyme is a promising strategy for a better control of hyperglycaemia in the context of type 2 diabetes. Glucopyranosylidene-spiro-heterocycles have been demonstrated as potent GP inhibitors, and more specifically spiro-oxathiazoles. A new synthetic route has now been elaborated through 1,3-dipolar cycloaddition of an aryl nitrile oxide to a glucono-thionolactone affording in one step the spiro-oxathiazole moiety. The thionolactone was obtained from the thermal rearrangement of a thiosulfinate precursor according to Fairbanks' protocols, although with a revisited outcome and also rationalised with DFT calculations. The 2-naphthyl substituted glucose-based spiro-oxathiazole 5h, identified as one of the most potent GP inhibitors (Ki = 160 nM against RMGPb) could be produced on the gram-scale from this strategy. Further evaluation in vitro using rat and human hepatocytes demonstrated that compound 5h is a anti-hyperglycaemic drug candidates performing slightly better than DAB used as a positive control. Investigation in Zucker fa/fa rat model in acute and subchronic assays further confirmed the potency of compound 5h since it lowered blood glucose levels by ～36% at 30 mg kg-1 and ～43% at 60 mg kg-1. The present study is one of the few in vivo investigations for glucose-based GP inhibitors and provides data in animal models for such drug candidates.
Selective S-deacetylation inspired by native chemical ligation: practical syntheses of glycosyl thiols and drug mercapto-analogues
Shu, Penghua,Zeng, Jing,Tao, Jinyi,Zhao, Yueqi,Yao, Guangmin,Wan, Qian
supporting information, p. 2545 - 2551 (2015/04/22)
Glycosyl thiols are useful building blocks for the construction of compounds of biological and synthetic importance. Herein, we report a practical synthetic approach toward the efficient synthesis of glycosyl thiols via chemo- and regioselective S-deacetylation inspired by native chemical ligation. This strategy allows the large scale synthesis of glycosyl thiols by simple purification steps without column chromatography. In addition, deacetylation reagents (DTT) could also be recovered and regenerated by a simple process. Thiol containing taxol and artemisinin analogues were successfully prepared based on this methodology. Finally, auranofin, a glucose-based oral drug used to treat rheumatoid arthritis, was synthesized in concise steps and overall high yields.
Simple synthesis of glycosylthiols and thioglycosides by rearrangement of O-glycosyl thionocarbamates
Komor,Kasprzycka,Pastuch-Gawo?ek,Szeja
, p. 37 - 42 (2014/08/18)
The synthesis of thioglycosides has been achieved in a high yielding process employing thionocarbamates prepared from protected reducing sugars and N-alkyl isothiocyanate in the presence of a non-nucleophilic base (K 2CO3). In the key step of the synthesis, thionocarbamates were treated with Lewis acid (TMSOTf) to give O,S-rearrangement products that were applied to the synthesis of both anomers of heteroaryl thioglycosides.
Stereoselective synthesis of β-glycosyl thiols and their synthetic applications
Jana, Manas,Misra, Anup Kumar
, p. 2680 - 2686 (2013/04/24)
A significantly fast reaction condition for the exclusive preparation β-glycosyl thiol derivatives has been developed successfully. The reaction condition is one-step, fast, high yielding, highly stereoselective, and requires only benchtop chemicals. Further reaction of glycosyl thiol derivatives with Michael acceptors and alkylating agents furnished thioglycosides and (1,1)-thiolinked trehalose analogs.
Exploring the native chemical ligation concept for highly stereospecific glycosylation reactions
Hoang, Kim Le Mai,Bai, Yaguang,Ge, Xin,Liu, Xue-Wei
, p. 5196 - 5204 (2013/07/25)
Various O-alkyl glycosides were obtained in a highly stereospecific manner with retention of configuration at the anomeric center. Our method has customized native chemical ligation concept for glycoconjugates synthesis, utilizing a meticulously controlle
From disulfide- to thioether-linked glycoproteins
Bernardes, Goncalo J. L.,Grayson, Elizabeth J.,Thompson, Sam,Chalker, Justin M.,Errey, James C.,El Oualid, Farid,Claridge, Timothy D. W.,Davis, Benjamin G.
supporting information; experimental part, p. 2244 - 2247 (2009/02/07)
(Chemical Presented) Strengthening the bond: The introduction of a thiol tag in combination with chemoselective ligation to form a disulfide-linked bioconjugate is a selective and useful method for site-selective protein glycosylation. The phosphine-mediated desulfurization of such glycoconjugates to their reductant-resistant thioether-linked counterparts completes a convergent, site-selective synthesis of thioether-linked glycoproteins (see scheme).
A novel stereoselective synthesis of 1,2-trans-thioaldoses
Xue, Weihua,Cheng, Xiaoyun,Fan, Jian,Diao, Huajia,Wang, Chunming,Dong, Lei,Luo, Yi,Chen, Jiangning,Zhang, Junfeng
, p. 6092 - 6095 (2008/03/12)
A mild and one-pot protocol for the efficient and stereoselective synthesis of 1,2-trans-aldosyl mercaptans is presented.
MMTr as an efficient anomeric S-protecting group for the synthesis of glycosyl thiols
Zhu, Xiangming
, p. 7935 - 7938 (2007/10/03)
The 4-monomethoxytrityl (MMTr) group was introduced in high yields to anomeric sulfhydryl functions using commercially available MMTrCl. Significantly, it is stable to a variety of reaction conditions, including acids and bases, and is removable under ver
The direct formation of glycosyl thiols from reducing sugars allows one-pot protein glycoconjugation
Bernardes, Goncalo J. L.,Gamblin, David P.,Davis, Benjamin G.
, p. 4007 - 4011 (2007/10/03)
(Figure Presented) Sweet and easy: A one-pot method consisting of direct thionation (1) followed by thiol-mediated chemoselective ligation (2) can be used for site-selective protein glycosylation. This procedure, which uses the Lawesson reagent, has been shown to be fully compatible with unprotected sugars, the products of which can be directly used in a selenenylsulfide protein glycosylation strategy.
Glycosyl disulfides: Novel glycosylating reagents with flexible aglycon alteration
Grayson, Elizabeth J.,Ward, Sarah J.,Hall, Alison L.,Rendle, Phillip M.,Gamblin, David P.,Batsanov, Andrei S.,Davis, Benjamin G.
, p. 9740 - 9754 (2007/10/03)
Glycosyl disulfides have been shown for the first time to be effective glycosyl donors. Glucosylation and galactosylation of a panel of representative alcohol acceptors allowed the formation of 28 simple glycosides, disaccharides, and glycoamino acids in yields of up to 90%. As well as providing a novel class of effective glycosyl donors, the ability to easily alter the nature of the aglycon and the ability to differently activate donors that differ only in their aglycon simply through altering conditions lends glycosyl disulfide donors to their use in latent-active reactivity tuning strategies.
