13096-62-3Relevant articles and documents
Syntheses of SGLT2 inhibitors by Ni- And Pd-catalyzed fukuyama coupling reactions
Kato, Daiki,Mashima, Kazushi,Nagae, Haruki,Seki, Masahiko,Talode, Jalindar,Tsurugi, Hayato
, p. 12382 - 12392 (2020)
Nickel- and palladium-catalyzed Fukuyama coupling reactions of a D-gluconolactone-derived thioester with arylzinc reagents at ambient temperature provided the corresponding multifunctional aryl ketones in high yield. Ligand screening for the nickel-catalyzed Fukuyama coupling reactions indicated that 1,2- bis(dicyclohexylphosphino)ethane (dCype) served as a superior supporting ligand to improve the product yield. In addition, Pd/C was a practical alternative that enabled ligand-free Fukuyama coupling reactions and was efficiently applied to the key C-C bond-forming step to prepare canagliflozin and dapagliflozin, which are diabetic SGLT2 inhibitors of current interest.
Tetra-n-propylammonium tetra-oxoruthenate(VII): A reagent of choice for the oxidation of diversely protected glycopyranoses and glycofuranoses to lactones
Benhaddou,Czernecki,Farid,Ville,Xie,Zegar
, p. 243 - 250 (1994)
2,3,4,6-Tetra-O-benzyl-D-glucopyranose, 2,3,5-tri-O-allyl-D-ribofuranose, 2,3,5-tri-O-allyl- and -tri-O-benzyl-D-arabinofuranose, and 2-deoxy-3,5-di- O-allyl-D-erythro-pentofuranose were oxidized to their corresponding lactones 6-10 by dimethyl sulfoxide activated by oxalyl chloride, pyridinium dichromate in the presence of molecular sieves and acetic acid, and tetra-n- propylammonium tetra-oxoruthenate(VII) using 4-methylmorpholine N-oxide as co-oxidant. With the latter reagent, analytically pure lactones were obtained in 83-98% yield. A multistep preparation of 3,4,6-tri-O-benzyl-2-deoxy-D- arabino-hexono-1,5-lactone (14) from 3,4,6-tri-O-benzyl-1,5-anhydro-2-deoxy- D-arabino-hex-1-enitol (65% overall yield) is described. 2,3,4,6-Tetra-O-benzyl-D-glucopyranose, 2,3,5-tri-O-allyl-D-ribofuranose, 2,3,5-tri-O-allyl- and -tri-O-benzyl-D-arabinofuranose, and 2-deoxy-3,5-di-O-allyl-D-erythro-pentofuranose were oxidized to their corresponding lactones 6-10 by dimethyl sulfoxide activated by oxalyl chloride, pyridinium dichromate in the presence of molecular sieves and acetic acid, and tetra-n-propylammonium tetra-oxoruthenate(VII) using 4-methylmorpholine N-oxide as co-oxidant. With the latter reagent, analytically pure lactones were obtained in 83-98% yield. A multistep preparation of 3,4,6-tri-O-benzyl-2-deoxy-D-arabino-hexono-1,5-lactone (14) from 3,4,6-tri-O-benzyl-1,5-anhydro-2-deoxy-D-arabino-hex-1-enitol (65% overall yield) is described.
Glucopyranosyl derivative and application thereof
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Paragraph 0260; 0272-0274, (2021/01/24)
The present invention relates to glucopyranosyl derivative and uses thereof. Specifically, the invention relates to a glucopyranosyl derivative used as a sodium-dependent glucose transporter 1(SGLT1)inhibitor and a pharmaceutically acceptable salt or stereoisomer thereof, and further relates to a pharmaceutical composition containing the derivative. The invention also relates to application of thecompound and the pharmaceutical composition thereof in preparation of drugs for treating diabetes and diabetes-related diseases.
Synthesis method of voglibose
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Paragraph 0060- 0061; 0075-0077, (2021/08/07)
The invention provides a synthesis method of voglibose, and solves the technical problems that in an existing synthesis method of voglibose, raw materials are difficult to obtain, high in price, large in investment, low in yield and not suitable for industrial production. The synthesis method comprises the steps: synthesizing a compound V by taking glucose monohydrate and sodium acetate as raw materials through eleven reaction steps; and preparing a compound VIII from the compound V through an addition reaction, a ring-opening reaction and an aldol condensation reaction, and thus obtaining voglibose through amination reduction of the compound VIII. The synthesis method of voglibose can be widely applied to the technical field of voglibose synthesis methods.
Method for continuously synthesizing benzyl-substituted glucolactone by adopting microchannel reaction device
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Page/Page column 0043; 0046; 0047; 0051; 0052-0053; 0056-0057; 0061, (2021/06/21)
The invention discloses a method for continuously synthesizing benzyl-substituted glucolactone by adopting a microchannel reaction device. The method comprises the following steps: taking methyl-alpha-D-mannopyranoside as an initial raw material, preparing the methyl-alpha-D-mannopyranoside into an old organic solvent solution, and reacting the old organic solvent solution with an organic solvent solution of benzyl chloride in a first microreactor to generate methyl glucose with hydroxyl protected by benzyl; reacting a homogeneous solution formed by mixing a reaction solution of benzyl-substituted gluconic acid and a small amount of hydrochloric acid solution in a second microreactor for demethylation to generate hydroxyl benzyl-substituted glucose; and finally, reacting the reaction solution with an aqueous solution of hydrogen peroxide and sodium hydroxide and an organic solvent solution of tetramethylpiperidine nitrogen oxide in a third microreactor to generate the high-purity hypoglycemic drug Dapagliflozin intermediate benzyl substituted glucolactone. The method disclosed by the invention is higher in heat and mass transfer efficiency and easier to industrially amplify, the initial materials are simple, cheap and easily available, the process is simple, the obtained intermediate is high in purity and high in yield, the production cost can be effectively reduced, and the method is suitable for industrial production.
Synthetic method of SGLT2 inhibitor intermediate
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Paragraph 0063; 0064, (2021/04/14)
The invention discloses a synthesis method of an SGLT2 inhibitor intermediate, which comprises the following steps: S1, oxidation: dissolving a compound I, adding into an oxidation system, carrying out liquid-liquid separation, and collecting an organic phase A to obtain a compound II; S2, dealkylation: adding the compound II into a dealkylation system to obtain a reaction solution, and performing liquid-liquid separation to obtain a compound III; S3, iodination: adding the compound III into an iodination system, performing liquid-liquid separation, and collecting an organic phase B to obtain a compound IV; S4, reduction: dissolving the compound IV, adding the dissolved compound IV into a reduction system, carrying out liquid-liquid separation, and collecting an organic phase C to obtain a target product V; the synthesis method has few synthesis steps, and the process is simple and easy to operate; expensive and dangerous compounds are not used in the synthesis process, and no safety risk exists; the total yield reaches 60 percent or higher; the method uses commercially available starting materials, is low in cost, ensures good reproducibility of a synthetic route, and is a process suitable for large-scale industrial production.
GLUCOPYRANOSYL DERIVATIVE AND USE THEREOF
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Paragraph 0242; 0263-0264, (2020/12/16)
The present invention relates to a glucopyranosyl derivative and a use thereof. In particular, the present invention relates to a glucopyranosyl derivative that is used as an inhibitor of sodium-dependent glucose transporters (SGLTs), particularly being used as an inhibitor of sodium-dependent glucose transporter-1 (SGLT1), and a pharmaceutically acceptable salt or stereoisomer thereof, further relating to a pharmaceutical composition containing the derivative. The present invention further relates to a use of the compound and a pharmaceutical composition thereof in the preparation of a drug for treating diabetes and diabetes-related diseases.
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
, 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.
GLUCOPYRANOSYL DERIVATIVE AND USE THEREOF
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Paragraph 00253, (2019/08/12)
Provided are a glucopyranosyl derivative as a sodium-dependent glucose transporters inhibitor, especially as a SGLT1 inhibitor, a pharmaceutically acceptable salt or a stereoisomer thereof, a pharmaceutical composition thereof, and the uses of the compound and pharmaceutical composition thereof in the preparation of drugs for the treatment of diabetes and diabetes-related diseases.
ANTI-EGFR ANTIBODY DRUG CONJUGATES
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Paragraph 1116, (2019/06/07)
The invention relates to anti-Epidermal Growth Factor Receptor (EGFR) antibody drug conjugates (ADCs) which inhibit Bcl-xL, including compositions and methods of using said ADCs.
