13096-62-3

Basic information

• Product Name: 2,3,4,6-TETRA-O-BENZYL-D-GLUCONO-1,5-LACTONE
• Synonyms: 2,3,4,6-TETRAKIS-O-(PHENYLMETHYL)-D-GLUCONIC ACID LACTONE;2,3,4,6-TETRA-O-BENZYL-D-GLUCONO-1,5-LACTONE;2,3,4,6-Tetrakis-O-(phenylmethyl)-D-Gluconic Acid, D-Lactone;2,3,4,6-Tetra-O-benzyl-D-glucono-1;5-lactone;D-Gluconic acid,2,3,4,6-tetrakis-O-(phenylMethyl)-, d-lactone;D-Gluconic acid, 2,3,4,6-tetrakis-O-(phenylMethyl)-, δ-lactone;2,3,4,6-tetra-O-benzyl-D-glucopyranolactone
• CAS NO: 13096-62-3
• Molecular Formula: C₃₄H₃₄O₆
• Molecular Weight: 538.63016
• Product Categories: Pharmaceutical Intermediates
• Mol File: 13096-62-3.mol
• Article Data: 93

Chemical Properties

• Boiling Point: 677.651 °C at 760 mmHg
• Flash Point: 283.08 °C
• Appearance: /
• Density: 1.22 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.614
• Storage Temp.: Sealed in dry,Room Temperature
• CAS DataBase Reference: 2,3,4,6-TETRA-O-BENZYL-D-GLUCONO-1,5-LACTONE(CAS DataBase Reference)
• NIST Chemistry Reference: 2,3,4,6-TETRA-O-BENZYL-D-GLUCONO-1,5-LACTONE(13096-62-3)
• EPA Substance Registry System: 2,3,4,6-TETRA-O-BENZYL-D-GLUCONO-1,5-LACTONE(13096-62-3)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• Hazardous Substances Data: 13096-62-3(Hazardous Substances Data)

Usage

Uses

2,3,4,6-Tetra-O-benzyl-D-glucono-1,5-lactone is used as a reactant to synthesize various glucoside containing compounds as selective SGLT2 inhibitors for the treatment of type 2 diabetes mellitus.

InChI:InChI=1/C34H34O6/c35-34-33(39-24-29-19-11-4-12-20-29)32(38-23-28-17-9-3-10-18-28)31(37-22-27-15-7-2-8-16-27)30(40-34)25-36-21-26-13-5-1-6-14-26/h1-20,30-33H,21-25H2/t30-,31-,32+,33-/m1/s1

Synthetic route

2,3,4,6-Tetra-O-benzyl-D-glucopyranose (4291-69-4, 6386-24-9, 6564-72-3, 59531-24-7, 69257-52-9, 78184-89-1, 78609-16-2, 78609-17-3, 78609-18-4, 96553-53-6, 104111-61-7, 131347-08-5, 4132-28-9) → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3)

Conditions	Yield
With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hydrogencarbonate; potassium bromide In dichloromethane; water at 0℃; for 0.333333h; Solvent;	100%
With 2,2,6,6-tetramethyl-piperidine-N-oxyl; sodium hypochlorite; sodium hydrogencarbonate; potassium bromide In dichloromethane; water at 0℃; for 0.333333h;	100%
With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hydrogencarbonate; potassium bromide In dichloromethane; water at 0℃; for 0.333333h;	100%

2,3,4,6-tetra-O-benzyl-D-glucopyranoside (59531-24-7) → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3)

Conditions	Yield
With acetic anhydride; dimethyl sulfoxide at 20℃;	93%
Stage #1: 2,3,4,6-tetra-O-benzyl-D-glucopyranoside In dimethyl sulfoxide at 20 - 25℃; for 0.5h; Inert atmosphere; Stage #2: With acetic anhydride at 15 - 25℃; Inert atmosphere;	92%
Stage #1: 2,3,4,6-tetra-O-benzyl-D-glucopyranoside With 4-methylmorpholine N-oxide In dichloromethane at 20℃; for 0.333333h; Molecular sieve; Stage #2: With tetrapropylammonium perruthennate In dichloromethane at 20℃; for 2h;	82%
Stage #1: 2,3,4,6-tetra-O-benzyl-D-glucopyranoside With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -78℃; for 105h; Stage #2: With triethylamine In dichloromethane at -78 - 20℃; for 1h;

2,3,4,6-tetra-O-benzyl-D-glucopyranose (6564-72-3) → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3)

Conditions	Yield
With acetic anhydride In dimethyl sulfoxide at 20℃;	89%
Stage #1: 2,3,4,6-tetra-O-benzyl-D-glucopyranose With 4-methylmorpholine N-oxide In dichloromethane at 20℃; for 0.333333h; Molecular sieve; Stage #2: With tetrapropylammonium perruthenate In dichloromethane at 20℃; for 2h;	82%
Stage #1: 2,3,4,6-tetra-O-benzyl-D-glucopyranose With 4-methylmorpholine N-oxide In dichloromethane at 20℃; for 0.333333h; Molecular sieve; Stage #2: tetrapropylammonium perruthennate In dichloromethane at 20℃; for 2h;	82%

(2R,3S,4R,5R)-N-benzyl-5-hydroxy-2,3,4,6-tetrabenzyloxyhexanamide (128984-82-7) → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3)

Conditions	Yield
Amberlite IR 120 H+ In 1,4-dioxane for 3h; Heating;	88%

2,3,4,6-tetra-O-benzoyl-D-glucopyranose (627466-64-2) → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3)

Conditions	Yield
With Dess-Martin periodane In dichloromethane at 20℃; for 0.5h; Oxidation;	85%

1-O-allyloxycarbonyl-2,3,4,6-tetra-O-benzyl-D-glucopyranose → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3)

Conditions	Yield
With palladium diacetate In acetonitrile at 80℃; for 2h;	60%

phenacyl 2,3,4,6-tetra-O-benzyl-α-D-glucopyranoside → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + (3R,4S,6R,7R,8S,9R)-7,8,9-Tris-benzyloxy-6-benzyloxymethyl-3-phenyl-1,5-dioxa-spiro[3.5]nonan-3-ol

Conditions	Yield
In benzene for 5h; Ambient temperature; Irradiation;	A 57% B 24%

phenacyl 2,3,4,6-tetra-O-benzyl-β-D-glucopyranoside (172986-43-5) → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + (3R,4S,6R,7R,8S,9R)-7,8,9-Tris-benzyloxy-6-benzyloxymethyl-3-phenyl-1,5-dioxa-spiro[3.5]nonan-3-ol

Conditions	Yield
In benzene for 5h; Ambient temperature; Irradiation;	A 56% B 20%

1-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)-tert-butyl sulfinothioate → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + 2,3,4,6-tetra-O-benzyl-D-glucono-δ-thionolactone (118206-39-6)

Conditions	Yield
In toluene at 110℃; Inert atmosphere;	A 45% B 45%

2,3,4,6-tetra-O-benzyl-D-mannono-1,5-lactone (82598-88-7) → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + <4S,5R>-2,4,6-tribenzyloxy-5-hydroxyhex-2-enoic acid-1,5-lactone (62641-00-3)

Conditions	Yield
With magnesium iodide In ethanol at 20℃; for 1h;	A 35% B 5%

2,3,4,6-tetra-O-benzyl-β-1-C-(2-thiazolyl)-D-glucopyranose (154127-55-6) → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3)

Conditions	Yield
With 4 A molecular sieve In toluene at 130℃; for 14h; closed vial; Yield given;

p-toluenesulfonyl chloride (98-59-9) + (5R,6R,7S,8R)-6,7,8-Tris-benzyloxy-5-benzyloxymethyl-1-methyl-4-oxa-1,2-diaza-spiro[2.5]octane → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + 1'-methyl-2'-[(Z)-2,3,4,6-tetra-O-benzyl-D-glucopyranosyllidene]toluene-4-sulfohydrazide

Conditions	Yield
With pyridine In dichloromethane for 3.5h; Title compound not separated from byproducts;

methyl 2,3,4,6-tetra-O-benzyl-α-D-glucopyranoside (3879-79-6, 17791-37-6, 19488-61-0, 53008-63-2, 61330-62-9, 69237-94-1, 69237-95-2, 71526-33-5, 83462-67-3, 84799-77-9, 103421-29-0, 103421-30-3, 139241-42-2) → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: TfOH / H2O 2: DMSO / acetic anhydride View Scheme
Multi-step reaction with 2 steps 1: hydrogenchloride; strontium (III) chloride hexahydrate / acetic acid; water / 70 °C 2: caesium carbonate; Iodine monochloride / dichloromethane / 3 h / 0 - 20 °C / Green chemistry View Scheme
Multi-step reaction with 2 steps 1: acetic acid; hydrogenchloride / water / 85 °C 2: acetic anhydride / dimethyl sulfoxide / 22 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: acetic acid; sulfuric acid / Reflux 2: acetic anhydride; dimethyl sulfoxide / 20 °C View Scheme
Multi-step reaction with 2 steps 1: acetic acid; sulfuric acid / water / 2 h / Reflux 2: acetic anhydride / dimethyl sulfoxide / 20 °C View Scheme

methyl-alpha-D-glucopyranoside (97-30-3) → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: sulfuric acid; acetic acid / water / 6 h / Reflux 2: acetic anhydride / dimethyl sulfoxide / 16 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 0 °C 1.2: 0 - 20 °C 2.1: hydrogenchloride; strontium (III) chloride hexahydrate / acetic acid; water / 70 °C 3.1: caesium carbonate; Iodine monochloride / dichloromethane / 3 h / 0 - 20 °C / Green chemistry View Scheme
Multi-step reaction with 3 steps 1.1: sodium hydride / mineral oil; N,N-dimethyl-formamide / 2 h / 0 - 20 °C / Inert atmosphere 1.2: 18 h / 20 °C / Inert atmosphere 2.1: acetic acid; hydrogenchloride / water / 85 °C 3.1: acetic anhydride / dimethyl sulfoxide / 22 h / 20 °C / Inert atmosphere View Scheme

D-glucose pentaacetate (83-87-4, 604-68-2, 604-69-3, 2152-77-4, 4026-35-1, 4163-59-1, 4163-60-4, 4163-61-5, 4163-65-9, 4257-94-7, 4257-96-9, 16299-15-3, 19186-39-1, 19189-55-0, 25878-60-8, 25941-03-1, 32445-48-0, 32445-49-1, 32445-53-7, 32445-54-8, 34685-58-0, 34685-59-1, 43168-42-9, 43168-44-1, 43169-22-8, 43169-25-1, 66966-07-2, 70749-17-6, 80184-01-6, 93221-01-3, 93221-02-4, 99630-88-3, 109215-53-4, 115792-70-6, 115792-73-9, 139894-92-1, 139973-25-4, 144071-49-8, 147648-81-5) → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: boron trifluoride diethyl etherate / dichloromethane / 0 - 20 °C / Inert atmosphere 2.1: methanol; sodium methylate / 20 °C 2.2: Amberlite.(R). IR-120 H+ ion exchange 3.1: sodium hydride / N,N-dimethyl-formamide / 2.5 h / 0 - 20 °C / Inert atmosphere 3.2: 12 h / 20 °C / Inert atmosphere 4.1: N-Bromosuccinimide; water / acetone / 3 h / 20 °C 5.1: acetic anhydride; dimethyl sulfoxide / 12 h / 30 °C View Scheme
Multi-step reaction with 5 steps 1: boron trifluoride diethyl etherate / dichloromethane / 12 h / 0 - 20 °C 2: sodium methylate; methanol 3: sodium hydride / N,N-dimethyl-formamide / 12 h / 0 - 20 °C 4: N-iodo-succinimide; water / acetone 5: acetic anhydride; dimethyl sulfoxide / 20 °C View Scheme

phenyl 2,3,4,5-tetra-O-benzyl-1-thio-β-D-glucopyranoside (38184-10-0) → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: N-Bromosuccinimide; water / acetone / 3 h / 20 °C 2: acetic anhydride; dimethyl sulfoxide / 12 h / 30 °C View Scheme

(2R,3S,4S,5R,6S)-2-Hydroxymethyl-6-phenylsulfanyl-tetrahydro-pyran-3,4,5-triol (2936-70-1, 5624-48-6, 13992-15-9, 16758-34-2, 28244-97-5, 77481-62-0, 77481-63-1, 105088-17-3, 149495-84-1) → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium hydride / N,N-dimethyl-formamide / 2.5 h / 0 - 20 °C / Inert atmosphere 1.2: 12 h / 20 °C / Inert atmosphere 2.1: N-Bromosuccinimide; water / acetone / 3 h / 20 °C 3.1: acetic anhydride; dimethyl sulfoxide / 12 h / 30 °C View Scheme

(2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(phenylthio)tetrahydro-2H-pyran-3,4,5-triyl triacetate (13992-16-0, 23661-28-1, 24404-53-3, 28512-68-7, 65236-85-3, 86782-39-0, 108032-93-5, 121524-01-4, 121570-34-1) → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: methanol; sodium methylate / 20 °C 1.2: Amberlite.(R). IR-120 H+ ion exchange 2.1: sodium hydride / N,N-dimethyl-formamide / 2.5 h / 0 - 20 °C / Inert atmosphere 2.2: 12 h / 20 °C / Inert atmosphere 3.1: N-Bromosuccinimide; water / acetone / 3 h / 20 °C 4.1: acetic anhydride; dimethyl sulfoxide / 12 h / 30 °C View Scheme

2-(allyloxy)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)-tetrahydro-2H-pyran (6207-45-0, 60478-61-7, 112344-80-6, 126924-14-9, 6207-44-9) → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium tert-butylate / N,N-dimethyl-formamide / 0.25 h / 70 °C 1.2: 2 h / 20 °C 2.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 0.25 h / -78 °C 2.2: -78 - 0 °C View Scheme

phenyl 2,3,4,6-tetra-O-acetyl-1-thio-α,β-D-glucopyranoside (13992-16-0, 23661-28-1, 24404-53-3, 28512-68-7, 65236-85-3, 86782-39-0, 108032-93-5, 121524-01-4, 121570-34-1) → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: sodium methylate; methanol 2: sodium hydride / N,N-dimethyl-formamide / 12 h / 0 - 20 °C 3: N-iodo-succinimide; water / acetone 4: acetic anhydride; dimethyl sulfoxide / 20 °C View Scheme

phenyl 1-thio-D-glucopyranoside (2936-70-1, 5624-48-6, 13992-15-9, 16758-34-2, 28244-97-5, 77481-62-0, 77481-63-1, 105088-17-3, 149495-84-1) → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium hydride / N,N-dimethyl-formamide / 12 h / 0 - 20 °C 2: N-iodo-succinimide; water / acetone 3: acetic anhydride; dimethyl sulfoxide / 20 °C View Scheme

phenyl 2,3,4,6-tetra-O-benzyl-1-thio-α/β-D-glucopyranoside (91602-61-8, 38184-10-0, 62774-37-2, 74801-29-9, 116501-52-1, 116501-53-2, 139974-84-8) → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: N-iodo-succinimide; water / acetone 2: acetic anhydride; dimethyl sulfoxide / 20 °C View Scheme

methyl 2,3,4,6-tetra-O-benzyl-D-glucopyranoside (84799-77-9) → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetic acid; water; sulfuric acid / 1 h / 110 °C 2: acetic anhydride; dimethyl sulfoxide / 18 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: hydrogenchloride; acetic acid / water / 5 h / 100 °C / Inert atmosphere 2: pyridinium chlorochromate / dichloromethane / 48 h / 20 °C / Inert atmosphere; Molecular sieve View Scheme

methyl D-glucopyranoside (97-30-3, 617-04-9, 709-50-2, 1824-94-8, 2152-78-5, 3396-99-4, 6819-48-3, 18469-06-2, 20550-04-3, 22277-65-2, 29411-57-2, 35437-40-2, 35437-43-5, 36191-11-4, 36191-12-5, 39598-79-3, 39598-80-6, 39598-89-5, 51023-63-3, 51223-62-2, 51224-38-5, 51224-39-6, 51224-40-9, 51224-41-0, 51819-81-9, 51819-82-0, 51819-83-1, 56688-81-4, 62279-53-2, 64281-79-4, 64281-80-7, 64912-19-2, 66101-73-3, 78184-90-4, 84368-39-8, 84368-40-1, 84368-41-2, 92142-37-5, 93302-26-2, 103421-28-9, 115794-08-6, 3149-68-6) → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: tetra-(n-butyl)ammonium iodide; sodium hydride / N,N-dimethyl-formamide; mineral oil / 3.5 h / 0 - 20 °C / Inert atmosphere 1.2: 20 h / 20 °C / Inert atmosphere 2.1: acetic acid; water; sulfuric acid / 1 h / 110 °C 3.1: acetic anhydride; dimethyl sulfoxide / 18 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: tetrahydrofuran / 0.33 h / 55 °C 2: hydrogenchloride / tetrahydrofuran / 0.25 h / 20 °C 3: sodium hydroxide; dihydrogen peroxide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical / water / 0.17 h / 65 °C View Scheme

benzyl bromide (100-39-0) → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: tetra-(n-butyl)ammonium iodide; sodium hydride / N,N-dimethyl-formamide; mineral oil / 3.5 h / 0 - 20 °C / Inert atmosphere 1.2: 20 h / 20 °C / Inert atmosphere 2.1: acetic acid; water; sulfuric acid / 1 h / 110 °C 3.1: acetic anhydride; dimethyl sulfoxide / 18 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 0 °C 1.2: 0 - 20 °C 2.1: hydrogenchloride; strontium (III) chloride hexahydrate / acetic acid; water / 70 °C 3.1: caesium carbonate; Iodine monochloride / dichloromethane / 3 h / 0 - 20 °C / Green chemistry View Scheme
Multi-step reaction with 3 steps 1.1: sodium hydride / mineral oil; N,N-dimethyl-formamide / 2 h / 0 - 20 °C / Inert atmosphere 1.2: 18 h / 20 °C / Inert atmosphere 2.1: acetic acid; hydrogenchloride / water / 85 °C 3.1: acetic anhydride / dimethyl sulfoxide / 22 h / 20 °C / Inert atmosphere View Scheme

(2S,3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-thiol (72174-24-4, 53269-97-9) → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + 2,3,4,6-tetra-O-benzyl-D-glucono-δ-thionolactone (118206-39-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine / toluene / 0.33 h / 20 °C / Inert atmosphere 2: toluene / 110 °C / Inert atmosphere View Scheme

O-ethyl S-(2,3,4,6-tetra-O-benzyl-D-glucopyranosyl) dithiocarbonate (53269-96-8, 116429-58-4, 116429-59-5, 130738-70-4, 141561-28-6) → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + 2,3,4,6-tetra-O-benzyl-D-glucono-δ-thionolactone (118206-39-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium / methanol / 2 h / 20 °C 2: triethylamine / toluene / 0.33 h / 20 °C / Inert atmosphere 3: toluene / 110 °C / Inert atmosphere View Scheme

benzyl chloride (100-44-7) → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: tetrahydrofuran / 0.33 h / 55 °C 2: hydrogenchloride / tetrahydrofuran / 0.25 h / 20 °C 3: sodium hydroxide; dihydrogen peroxide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical / water / 0.17 h / 65 °C View Scheme

n-butyllithium (109-72-8, 29786-93-4) + (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) → 2,3,4,6-tetra-O-benzyl-1-C-butyl-D-glucopyranose

Conditions	Yield
at -78℃;	100%
In tetrahydrofuran; toluene at -50℃; for 2h;	72%

(3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + phenyllithium (591-51-5) → (2,3,4,6-tetra-O-benzyl-1-C-phenyl)-D-glucopyranose (118436-89-8, 118436-90-1)

Conditions	Yield
at -78℃;	100%
In tetrahydrofuran 1.) -78 deg C, 2 h, 2.) from -78 deg C to room temperature, 2 h;	85.7%
In tetrahydrofuran at -78℃;

(3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + (3-methylindol-1-yl)magnesium bromide → (2R,3S,4R,5R)-2,3,4,6-Tetrakis-benzyloxy-5-hydroxy-1-(3-methyl-indol-1-yl)-hexan-1-one

Conditions	Yield
In tetrahydrofuran; toluene at -20℃;	100%

(3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) → (3R,4S,5R,6R)-3,4,5-trisbenzyloxy-6-benzyloxymethyl-2-[3-(5-ethylbenzo[b]thiophen-2-yl-methyl)naphthalen-1-yl]tetrahydropyran-2-ol (874357-34-3)

Conditions	Yield
Stage #1: 2-(4-bromo-naphthalen-2-ylmethyl)-5-ethylbenzo[b]thiophene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.0833333h; Stage #2: (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one In tetrahydrofuran; hexane at -78℃; for 0.0833333h;	100%

(3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + ((3-bromo-4-fluorobenzyl)oxy)(tert-butyl)dimethylsilane (655237-57-3) → 2,3,4,6-tetra-O-benzyl-1-C-[5-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]-D-glucopyranose

Conditions	Yield
Stage #1: ((3-bromo-4-fluorobenzyl)oxy)(tert-butyl)dimethylsilane With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one In tetrahydrofuran; hexane at -78℃; for 1h;	100%

(3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + 2-[(5-bromo-2-methyl-phenyl)methyl]-5-(4-fluorophenyl)thiophene (1030825-20-7) → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)-2-(3-((5-(4-fluorophenyl)thiophen-2-yl)methyl)-4-methylphenyl)tetrahydro-2H-pyran-2-ol

Conditions	Yield
Stage #1: 3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl bromide With n-butyllithium In tetrahydrofuran at -78℃; for 1h; Inert atmosphere; Stage #2: (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one In tetrahydrofuran at 20℃; for 3h;	99%

(3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + 1,3,5-trifluorobenzene (372-38-3) → (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)-2-(2,4,6-trifluorophenyl)tetrahydro-2H-pyran-2-ol

Conditions	Yield
Stage #1: 1,3,5-trifluorobenzene With n-butyllithium In diethyl ether at -78℃; for 1h; Inert atmosphere; Stage #2: (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one In diethyl ether at -78℃; for 0.25h; Inert atmosphere; Stage #3: With acetic acid In diethyl ether at -78℃; for 0.166667h; Inert atmosphere;	98%

(3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) → 2,3,4,6-tetra-O-benzyl-D-gluconamide (76670-93-4)

Conditions	Yield
With ammonia In methanol at 0℃; for 2h;	97%
With ammonia In methanol	96%
With ammonia In methanol at 0℃; for 3h;	96%

(3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + trans-2-propenyl bromide (590-15-8) → (3R,4S,5R,6R)-3,4,5-Tris-benzyloxy-6-benzyloxymethyl-2-prop-1-ynyl-tetrahydro-pyran-2-ol

Conditions	Yield
With n-butyllithium In tetrahydrofuran at -78℃;	97%

(3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + propylene glycol (57-55-6) → 1,2-O-(2,3,4,6-tetra-O-benzyl-D-glucopyranosylidene)-1,2-propanediol (77855-88-0, 77881-86-8)

Conditions	Yield
With sulfuric acid In benzene for 24h; Heating;	96.2%

(3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + O-(tert-butyl)hydroxylamine hydrochloride → 1N-tert-butoxy-2,3,4,6-tetrakis(benzyloxy)-5-hydroxy-(2R,3S,4R,5R)-hexanamide

Conditions	Yield
With trimethylaluminum In dichloromethane at 20℃; for 1h; Alkoxyamination;	96%

(3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) → <4S,5R>-2,4,6-tribenzyloxy-5-hydroxyhex-2-enoic acid-1,5-lactone (62641-00-3)

Conditions	Yield
With sodium hydride; acetophenone In tetrahydrofuran 1.) 45 deg C, 30 min, 2.) 25 deg C, 5 min.;	95%
With sodium methylate In methanol for 0.5h; Ambient temperature;	40 mg

(3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + dimethyl methane phosphonate (756-79-6) → 3,4,5,7-Tetra-O-benzyl-1-deoxy-1-(dimethoxyphosphoryl)-α-D-gluco-2-heptulopyranose (140926-87-0)

Conditions	Yield
With n-butyllithium In tetrahydrofuran; hexane at -78 - -70℃; for 1h;	95%
With n-butyllithium	92%
Stage #1: dimethyl methane phosphonate With n-butyllithium In tetrahydrofuran; hexane at -70℃; for 0.333333h; Metallation; Stage #2: (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one In tetrahydrofuran; hexane at -70 - -40℃; for 1h; Addition;	91%
Stage #1: dimethyl methane phosphonate With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one In tetrahydrofuran; hexane at -78 - 0℃; Stage #3: With ammonium chloride In tetrahydrofuran; hexane; water; ethyl acetate cooling with ice;

(3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + tert-butyl 2-(bromomethyl)acrylate (53913-96-5) → 2-((2S,3R,4S,5R,6R)-3,4,5-Tris-benzyloxy-6-benzyloxymethyl-2-hydroxy-tetrahydro-pyran-2-ylmethyl)-acrylic acid tert-butyl ester

Conditions	Yield
With samarium diiodide In tetrahydrofuran at 20℃;	95%

(3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + N-methoxylamine hydrochloride (593-56-6) → 1N-methoxy-2,3,4,6-tetrakis(benzyloxy)-5-hydroxy-(2R,3S,4R,5R)-hexanamide

Conditions	Yield
With trimethylaluminum In dichloromethane at 20℃; for 1h; Alkoxyamination;	95%

(3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + ethyl acetate (141-78-6) → 2-deoxy-4,5,6,8-tetra-O-benzyl-α-D-gluco-3,7-pyranoso-3-octulosonate (132470-52-1)

Conditions	Yield
With lithium hexamethyldisilazane	95%
Stage #1: ethyl acetate With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -60℃; for 0.25h; Stage #2: (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one In tetrahydrofuran; hexane at -60 - 20℃; for 1h; Further stages.;	66%

(3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + benzylmagnesium chloride (6921-34-2) → 1-C-benzyl-2,3,4,6-tetra-O-benzyl-α-D-glucopyranose (389121-73-7)

Conditions	Yield
	95%

(3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + phenylmagnesium bromide (1589-82-8) → 1-C-benzyl-2,3,4,6-tetra-O-benzyl-α-D-glucopyranose (389121-73-7)

Conditions	Yield
In tetrahydrofuran; diethyl ether at -78 - -40℃; for 2h;	95%

n-butyllithium (109-72-8, 29786-93-4) + (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) → 2,3,4,6-tetra-O-benzyl-1-C-n-butyl-α-D-glucopyranose (292149-85-0)

Conditions	Yield
Stage #1: n-butyllithium; (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one In tetrahydrofuran; hexane at -78℃; for 2h; Stage #2: With water In tetrahydrofuran; hexane Further stages.;	95%
In tetrahydrofuran; hexane at -78℃; for 0.5h; diastereoselective reaction;	92%

(3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + allyl bromide (106-95-6) → (3R,4S,5R,6R)-2,2-diallyl-3,4,5-tris(benzyloxy)-6-(benzyloxy)methyltetrahydropyran

Conditions	Yield
With chloro-trimethyl-silane; zinc In tetrahydrofuran at 20℃; for 4h; Barbier Coupling Reaction;	95%

(3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + dichloromethane (75-09-2) → 2,3,4,6-Tetra-O-benzyl-1-C-(dichloromethyl)-α-D-glucopyranose (140658-50-0)

Conditions	Yield
With lithium diisopropyl amide In tetrahydrofuran; hexane at -75 - -70℃; for 1h;	94%

(3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + 2,2-Dimethyl-1,3-propanediol (126-30-7) → 2,3,4,6-tetra-O-benzyl-5',5'-dimethylspiro[1,5-anhydro-D-glucitol-1,2'-[1,3]dioxane] (261713-59-1)

Conditions	Yield
With Trimethylmethoxysilane; trimethylsilyl trifluoromethanesulfonate In toluene at 20℃; for 1h;	94%
With Trimethylmethoxysilane; trimethylsilyl trifluoromethanesulfonate In toluene at 20℃; for 2h; Cycloaddition;	94%

(3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + methyllithium (917-54-4) → 3,4,5,7-tetra-O-benzyl-1-deoxy-α-D-gluco-hept-2-ulopyranose (137344-41-3)

Conditions	Yield
In tetrahydrofuran; diethyl ether at -78℃; for 0.5h; diastereoselective reaction;	94%
In tetrahydrofuran; diethyl ether at -78℃; for 1h;	83%
In tetrahydrofuran at -78℃; for 0.166667h;	67%

(3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + Cp2TiMe2 → 2,6-anhydro-3,4,5,7-tetra-O-benzyl-1-deoxy-D-gluco-hept-1-enitol (133697-34-4, 97321-70-5)

Conditions	Yield
In toluene	94%
In toluene at 65 - 70℃; for 14h;

(3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + methyl 7,7-dibromo-6,7-dideoxy-2,3,4-tri-O-benzyl-α-D-gluco-hept-6-enopyranoside (89160-10-1) → (3R,4S,5R,6R)-3,4,5-Tris-benzyloxy-6-benzyloxymethyl-2-((2R,3R,4S,5R,6S)-3,4,5-tris-benzyloxy-6-methoxy-tetrahydro-pyran-2-ylethynyl)-tetrahydro-pyran-2-ol

Conditions	Yield
With n-butyllithium In tetrahydrofuran; hexane at -50℃;	93%
With n-butyllithium In tetrahydrofuran at -50℃; for 1h;	92%

(3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + N-benzyloxyamine (622-33-3) → 1N-benzyloxy-2,3,4,6-tetrakis(benzyloxy)-5-hydroxy-(2R,3S,4R,5R)-hexanamide (270062-18-5)

Conditions	Yield
With trimethylaluminum In dichloromethane at 20℃; for 1h; Alkoxyamination;	93%
Stage #1: (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one; N-benzyloxyamine In dichloromethane at 20℃; for 0.5h; Stage #2: With trimethylaluminum In hexane; dichloromethane at 20℃; for 1h; Further stages.;	93%

(3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + O-ethylhydroxylamine hydrochloride (3332-29-4) → 1N-ethoxy-2,3,4,6-tetrakis(benzyloxy)-5-hydroxy-(2R,3S,4R,5R)-hexanamide

Conditions	Yield
With trimethylaluminum In dichloromethane at 20℃; for 1h; Alkoxyamination;	93%

(3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one (13096-62-3) + tert-butyl 4-iodobenzoate (120363-13-5) → 1-C-(4-tert-butoxycarbonylphenyl)-2,3,4,6-tetra-O-benzyl-α-D-glucopyranose

Conditions	Yield
With n-butyllithium; 2,4,6-triisopropyl-1-bromobenzene In tetrahydrofuran at -78℃; for 1h; Reagent/catalyst; Barbier Coupling Reaction; Inert atmosphere; stereoselective reaction;	93%
Stage #1: (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one; tert-butyl 4-iodobenzoate With 2,4,6-triisopropylphenyl lithium In tetrahydrofuran at -78℃; Stage #2: With ammonium chloride In water	93%

Upstream product

• 172986-43-5 phenacyl 2,3,4,6-tetra-O-benzyl-β-D-glucopyranoside 
• 154127-55-6 2,3,4,6-tetra-O-benzyl-β-1-C-(2-thiazolyl)-D-glucopyranose 
• 6207-45-0 2-(allyloxy)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)-tetrahydro-2H-pyran 
• 84799-77-9 methyl 2,3,4,6-tetra-O-benzyl-D-glucopyranoside 
• 97-30-3 methyl D-glucopyranoside 
• 100-39-0 benzyl bromide 
• 100-44-7 benzyl chloride 
• 131531-76-5 p-methylphenyl 2,3,4,6-tetra-O-benzyl-thio-β-D-glucopyranoside 
• 604-69-3 β-D-glucose pentaacetate 
• 1152-39-2 p-methylphenyl 1-thio-β-D-glucopyranoside 
• 28244-94-2 p-tolyl-2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranoside 
• 53269-96-8 O-ethyl S-(2,3,4,6-tetra-O-benzyl-D-glucopyranosyl) dithiocarbonate 
• 72174-24-4 (2S,3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-thiol 
• 91602-61-8 phenyl 2,3,4,6-tetra-O-benzyl-1-thio-α/β-D-glucopyranoside 

Downstream Products

• 154127-55-6 2,3,4,6-tetra-O-benzyl-β-1-C-(2-thiazolyl)-D-glucopyranose 
• 77855-89-1 2,3,4,6-tetra-O-benzylspiro[1,5-anhydro-D-glucitol-1,2'-[1,3]dioxolane] 
• 118436-89-8 (2,3,4,6-tetra-O-benzyl-1-C-phenyl)-D-glucopyranose 
• 128984-82-7 (2R,3S,4R,5R)-N-benzyl-5-hydroxy-2,3,4,6-tetrabenzyloxyhexanamide 
• 121209-13-0 (3R,4S,5R,6R)-N-Benzyl-3,4,5-tris(benzyloxy)-6-<(benzyloxy)methyl>piperidin-2-one; Pentabenzyl-D-nojirilactam 
• 77855-88-0 1,2-O-(2,3,4,6-tetra-O-benzyl-D-glucopyranosylidene)-1,2-propanediol 
• 77855-87-9 1,2-O-(2,3,4,6-tetra-O-benzyl-D-glucopyranosylidene)-3-chloro-1,2-propanediol 
• 72333-35-8 methyl 4,6-O-(2,3,4,6-tetra-O-benzyl-D-glucopyranosylidene)-2,3-di-O-methyl-α-D-glucopyranoside 
• 133191-78-3 3,4,5,7-tetra-O-benzyl-1-O-(methoxymethyl)-α-D-gluco-2-heptulopyranose 
• 173170-15-5 2,3,4,6-tetra-O-benzyl-1-C-(1H-imidazol-2-yl)-α-D-glucopyranose 
• 776313-98-5 5,6,7,9-tetra-O-benzyl-1,2,3-trideoxy-D-gluco-non-1-eno-4-ulopyranose 
• 133697-34-4 2,6-anhydro-3,4,5,7-tetra-O-benzyl-1-deoxy-D-gluco-hept-1-enitol 
• 166828-15-5 4,5,6,8-tetra-O-benzyl-1,2-dideoxy-α-D-gluco-oct-1-eno-3-ulopyranose 

Relevant articles and documents

Syntheses of SGLT2 inhibitors by Ni- And Pd-catalyzed fukuyama coupling reactions

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.

Glucopyranosyl derivative and application thereof

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.

Method for continuously synthesizing benzyl-substituted glucolactone by adopting microchannel reaction device

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.

GLUCOPYRANOSYL DERIVATIVE AND USE THEREOF

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.