73960-72-2

Basic information

• Product Name: Methyl5-acetamido-4,7,8,9-tetra-O-acetyl-2,6-anhydro-3,5-dideoxy-D-glycero-D-galacto-non-2-enonate
• Synonyms: Methyl5-acetamido-4,7,8,9-tetra-O-acetyl-2,6-anhydro-3,5-dideoxy-D-glycero-D-galacto-non-2-enonate;Methyl 2,3-didehydro-4,7,8,9-tetera-O-acetyl-N-acetylneuraminate;Methyl 2,3-Didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate
• CAS NO: 73960-72-2
• Molecular Formula: C20H27NO12
• Molecular Weight: 473.428
• Product Categories: Carbohydrates & Derivatives
• Mol File: 73960-72-2.mol
• Article Data: 81

Chemical Properties

• Melting Point: 126-127℃
• Boiling Point: 571.8 °C at 760 mmHg
• Flash Point: 299.6 °C
• Appearance: /
• Density: 1.31
• PKA: 13.69±0.70(Predicted)
• CAS DataBase Reference: Methyl5-acetamido-4,7,8,9-tetra-O-acetyl-2,6-anhydro-3,5-dideoxy-D-glycero-D-galacto-non-2-enonate(CAS DataBase Reference)
• NIST Chemistry Reference: Methyl5-acetamido-4,7,8,9-tetra-O-acetyl-2,6-anhydro-3,5-dideoxy-D-glycero-D-galacto-non-2-enonate(73960-72-2)
• EPA Substance Registry System: Methyl5-acetamido-4,7,8,9-tetra-O-acetyl-2,6-anhydro-3,5-dideoxy-D-glycero-D-galacto-non-2-enonate(73960-72-2)

Safety Data

• Hazardous Substances Data: 73960-72-2(Hazardous Substances Data)

Usage

Chemical Properties

Pale Yellow Solid

Synthetic route

disodium hydrogenphosphate + N-acetyl-4,7,8,9-tetra-O-acetyl-2-chloro-2-deoxyneuraminic acid methyl ester (67670-69-3) → methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2)

Conditions	Yield
In acetonitrile for 3h; Reflux;	100%

4-nitro-phenol (100-02-7) + N-acetyl-4,7,8,9-tetra-O-acetyl-2-chloro-2-deoxyneuraminic acid methyl ester (67670-69-3) → methyl (4-nitrophenyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-oxy-α-D-glycero-D-galacto-2-nonulopyranosid)onate (59694-37-0) + methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile for 3h; Ambient temperature;	A 98% B 2%

N-acetyl-4,7,8,9-tetra-O-acetyl-2-chloro-2-deoxyneuraminic acid methyl ester (67670-69-3) → methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2)

Conditions	Yield
With disodium hydrogenphosphate In acetonitrile for 3h; Heating;	95%
With triethylamine In dichloromethane at 20℃; for 2h; Molecular sieve; Schlenk technique;	91%
With 1,8-diazabicyclo[5.4.0]undec-7-ene In benzene at 20℃; for 14h;	83%

(1S,2R)-1-((2R,3R,4S,6R)-3-acetamido-4,6-diacetoxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)propane-1,2,3-triyl triacetate (108740-39-2, 6931-68-6, 72690-21-2, 73208-82-9, 108740-37-0, 108740-38-1, 119241-63-3, 119241-64-4, 119241-65-5, 147129-72-4, 147129-73-5, 74006-95-4) → methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2)

Conditions	Yield
In dichloromethane at 420℃; under 48.7549 - 67.5068 Torr; Pyrolysis;	95%
With trimethylsilyl trifluoromethanesulfonate In acetonitrile for 5h;	90%
With trimethylsilyl trifluoromethanesulfonate In ethyl acetate at 0 - 20℃; for 4h; Inert atmosphere;	89%

methyl 5-acetamido-3,4,7,8,9-penta-O-acetyl-2,6-anhydro-5-deoxy-D-arabino-L-gulo-nononate (114103-01-4) → methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2)

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In chloroform for 48h; Heating;	95%

(4S,5R,6R)-4-Acetoxy-5-acetylamino-2-phenylsulfanyl-6-((1S,2R)-1,2,3-triacetoxy-propyl)-tetrahydro-pyran-2-carboxylic acid methyl ester (155155-64-9) → methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2)

Conditions	Yield
Stage #1: (4S,5R,6R)-4-Acetoxy-5-acetylamino-2-phenylsulfanyl-6-((1S,2R)-1,2,3-triacetoxy-propyl)-tetrahydro-pyran-2-carboxylic acid methyl ester With dimethyl-(methylthio)-sulphonium trifluoromethanesulphonate In dichloromethane at -20℃; for 2h; Substitution; Stage #2: With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at -20 - 20℃; Elimination;	95%

methyl 5-acetamido-2,4,7,8,9-penta-O-acetyl-3,5-dideoxy-D-glycero-D-galacto-2-nonulopyranosonate (6931-68-6, 72690-21-2, 74006-95-4, 108740-37-0, 108740-38-1, 108740-39-2, 119241-63-3, 119241-64-4, 119241-65-5, 147129-72-4, 147129-73-5, 73208-82-9) → methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2)

Conditions	Yield
With trimethylsilyl trifluoromethanesulfonate In acetonitrile at 2℃; for 6h;	92%
With triphenylphosphine hydrobromide In acetonitrile at 60℃; for 4h;	90%
With triphenylphosphine hydrobromide In acetonitrile at 60℃; for 20h; Inert atmosphere;	88%

(4S,5R,6R)-4-Acetoxy-5-acetylamino-2-phenylselanyl-6-((1S,2R)-1,2,3-triacetoxy-propyl)-tetrahydro-pyran-2-carboxylic acid methyl ester → methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2)

Conditions	Yield
Stage #1: (4S,5R,6R)-4-Acetoxy-5-acetylamino-2-phenylselanyl-6-((1S,2R)-1,2,3-triacetoxy-propyl)-tetrahydro-pyran-2-carboxylic acid methyl ester With dimethyl-(methylthio)-sulphonium trifluoromethanesulphonate In dichloromethane at -20℃; for 2h; Substitution; Stage #2: With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at -20 - 20℃; Elimination;	92%

acetyl chloride (75-36-5) + N-acetyl neuraminic acid (19342-33-7) → methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2)

Conditions	Yield
Stage #1: N-acetyl neuraminic acid In methanol at 60℃; for 16h; Inert atmosphere; Stage #2: acetyl chloride at 0 - 20℃; for 48h; Inert atmosphere; Sealed tube; Stage #3: With disodium hydrogenphosphate at 90℃; for 16h; Inert atmosphere;	92%

7-hydroxy-4-methyl-chromen-2-one (90-33-5, 79566-13-5) + N-acetyl-4,7,8,9-tetra-O-acetyl-2-chloro-2-deoxyneuraminic acid methyl ester (67670-69-3) → Methyl (4-methylcoumarin-7-yl-5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-α-D-glycero-D-galacto-2-nonulopyranosid)onate (59361-08-9) + methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile for 3h; Ambient temperature;	A 90% B 5%

methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-D-galacto-2-nonulopyranosonate 2-(N-phenyl)trifluoroacetimidate (874904-90-2) → methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2)

Conditions	Yield
With trimethylsilyl trifluoromethanesulfonate; C22H29NO10S In propiononitrile at -78℃; Molecular sieve;	90%

(4S,5R,6R)-4-Acetoxy-5-acetylamino-2-phenylsulfanyl-6-((1S,2R)-1,2,3-triacetoxy-propyl)-tetrahydro-pyran-2-carboxylic acid methyl ester (155155-64-9) → methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) + [methyl (5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-α-D-glycero-D-galacto-2-nonulopyranosyl)onate] phenyl sulfone (121512-93-4) + phenyl sulfone

Conditions	Yield
With pyridine; 3-chloro-benzenecarboperoxoic acid In dichloromethane at 4℃; for 23.5h; Title compound not separated from byproducts;	A 88% B n/a C n/a

(4S,5R,6R)-4-Acetoxy-5-acetylamino-2-(bis-benzyloxy-phosphanyloxy)-6-((1S,2R)-1,2,3-triacetoxy-propyl)-tetrahydro-pyran-2-carboxylic acid methyl ester → methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2)

Conditions	Yield
With trimethylsilyl trifluoromethanesulfonate; 3 A molecular sieve In acetonitrile at -40℃;	83%
With trimethylsilyl trifluoromethanesulfonate; C37H66F3NO8SSi3 In acetonitrile at -40℃; Molecular sieve;	83%

methyl (phenyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycerol-β-D-galactonon-2-ulopyranoside)onate (118977-25-6) → methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) + [methyl (5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-α-D-glycero-D-galacto-2-nonulopyranosyl)onate] phenyl sulfone (121512-93-4) + phenyl sulfone

Conditions	Yield
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 4℃; for 0.5h; Title compound not separated from byproducts;	A 82% B n/a C n/a
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 4℃; for 23h; Title compound not separated from byproducts;

methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-2,3-dibromo-2,3,5-trideoxy-β-D-erythro-L-manno-non-2-ulopyranosonate (108999-04-8) → methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2)

Conditions	Yield
With water; sodium iodide In acetonitrile at 20℃; for 2h; Reagent/catalyst; Solvent; Temperature;	82%

methyl (5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-β-D-glycero-D-galacto-2-nonulopyranosyl)onate (20298-34-4, 84380-10-9) → methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2)

Conditions	Yield
With N,N,N,N,N,N-hexamethylphosphoric triamide; thionyl chloride In benzene at 80℃; for 7h;	81%
Multi-step reaction with 2 steps 1: 79 percent / pyridine / CH2Cl2 / 5 h / 0 °C 2: 6 percent / Me2SiCl2, AgClO4 / various solvent(s); toluene / 3 h / -35 °C View Scheme

methyl (phenyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-galacto-2-nonulopyranoside)onate (118977-25-6, 118977-26-7) → methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2)

Conditions	Yield
Stage #1: methyl (phenyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-galacto-2-nonulopyranoside)onate In dichloromethane at -40℃; for 16h; Molecular sieve; Inert atmosphere; Stage #2: With N-iodo-succinimide; trifluorormethanesulfonic acid In dichloromethane at 20℃; for 1h; Molecular sieve; Inert atmosphere;	79%

potassium ethyl xanthogenate (140-89-6) + N-acetyl-4,7,8,9-tetra-O-acetyl-2-chloro-2-deoxyneuraminic acid methyl ester (67670-69-3) → O-ethyl S-[methyl (5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-α-D-glycero-D-galacto-2-nonulopyranosyl)onate] dithiocarbonate (121512-94-5) + methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2)

Conditions	Yield
In ethanol Ambient temperature; in dark;	A 71% B n/a

(1S,2R)-1-((2R,3R,4S,6R)-3-acetamido-4,6-diacetoxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)propane-1,2,3-triyl triacetate (108740-39-2, 6931-68-6, 72690-21-2, 73208-82-9, 108740-37-0, 108740-38-1, 119241-63-3, 119241-64-4, 119241-65-5, 147129-72-4, 147129-73-5, 74006-95-4) → methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) + methyl (3aS,4R,7aR)-4-[(1S,2R)-1,2,3-triacetoxy-propyl]-2-methyl-3a,7a-dihydro-4H-pyrano[3,4-d][1,3]oxazole-6-carboxylate (78850-37-0)

Conditions	Yield
With trimethylsilyl trifluoromethanesulfonate In nitromethane at 4℃; for 15h;	A 69% B 15%
With boron trifluoride diethyl etherate In acetonitrile at 25℃; for 1.5h; Inert atmosphere; chemoselective reaction;	A 83 %Spectr. B 9 %Spectr.
With boron trifluoride diethyl etherate In dichloromethane at 20℃; Inert atmosphere; chemoselective reaction;	A 1 %Spectr. B 92 %Spectr.

methyl (methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycero-α-D-galacto-2-nonulopyranosid)onate10,13 (116450-06-7) + 2-(trimethylsilyl)ethyl 3-O-benzoyl-β-D-galactopyranoside (121377-24-0) → methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) + 2-(trimethylsilyl)ethyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2->6)-3-O-benzoyl-β-D-galactopyranoside (121377-28-4)

Conditions	Yield
With dimethyl-(methylthio)-sulphonium trifluoromethanesulphonate In acetonitrile at -15℃; for 15h;	A n/a B 68%

N-acetyl-4,7,8,9-tetra-O-acetyl-2-chloro-2-deoxyneuraminic acid methyl ester (67670-69-3) + 1,2:3,4-di-O-isopropylidene-α-D-galactopyranose (4064-06-6) → O- (116113-13-4, 89733-58-4) + methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2)

Conditions	Yield
With silver (II) carbonate In dichloromethane -20 deg C 15 hour, room temp. 50 hour.; Title compound not separated from byproducts;	A 67% B 3%

(1S,2R)-1-((2R,3R,4S,6R)-3-acetamido-4,6-diacetoxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)propane-1,2,3-triyl triacetate (108740-39-2, 6931-68-6, 72690-21-2, 73208-82-9, 108740-37-0, 108740-38-1, 119241-63-3, 119241-64-4, 119241-65-5, 147129-72-4, 147129-73-5, 74006-95-4) → methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) + (2S,4S,5R,6R)-4-Acetoxy-5-acetylamino-2-cyclohexylmethoxy-6-((1S,2R)-1,2,3-triacetoxy-propyl)-tetrahydro-pyran-2-carboxylic acid methyl ester + (2R,4S,5R,6R)-4-Acetoxy-5-acetylamino-2-cyclohexylmethoxy-6-((1S,2R)-1,2,3-triacetoxy-propyl)-tetrahydro-pyran-2-carboxylic acid methyl ester

Conditions	Yield
With tetrachlorosilane; silver trifluoromethanesulfonate; cyclohexylmethyl trimethylsilyl ether In various solvent(s) at 0℃; for 19h; Yields of byproduct given;	A 66% B n/a C n/a

O-ethyl S-[methyl (5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-α-D-glycero-D-galacto-2-nonulopyranosyl)onate] dithiocarbonate (121512-94-5) → methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2)

Conditions	Yield
In 1,2-dichloro-ethane for 15h; Inert atmosphere; Photolysis;	66%

sialyl xanthate → methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2)

Conditions	Yield
With di-tert-butyl nitroxide In 1,2-dichloro-ethane Photolysis; Inert atmosphere;	66%

(2S,4S,5R,6R)-4-Acetoxy-5-acetylamino-2-(toluene-4-sulfinyl)-6-((1S,2R)-1,2,3-triacetoxy-propyl)-tetrahydro-pyran-2-carboxylic acid methyl ester → methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2)

Conditions	Yield
In toluene Heating;	62%

2-(Trimethylsilyl)ethyl-6-O-benzoyl-β-D-galactopyranoside (121377-26-2) + methyl (methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycero-D-galacto-2-nonulopyranosid)onate (144240-36-8) → methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) + 2-(trimethylsilyl)ethyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2->3)-6-O-benzoyl-β-D-galactopyranoside (121377-30-8)

Conditions	Yield
With dimethyl-(methylthio)-sulphonium trifluoromethanesulphonate In acetonitrile at -15℃; for 17h;	A n/a B 52%

methyl (2-p-methylphenyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α/β-D-galacto-2-thio-nonulopyranosid)onate (1071226-27-1) + 4-methoxyphenyl 2,6-di-O-benzyl-β-D-galactopyranoside (159922-50-6) → methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) + (2S,4S,5R,6R)-4-Acetoxy-5-acetylamino-2-[(2S,3R,4S,5S,6R)-3-benzyloxy-6-benzyloxymethyl-5-hydroxy-2-(4-methoxy-phenoxy)-tetrahydro-pyran-4-yloxy]-6-((1S,2R)-1,2,3-triacetoxy-propyl)-tetrahydro-pyran-2-carboxylic acid methyl ester

Conditions	Yield
With N-iodo-succinimide; trifluorormethanesulfonic acid In acetonitrile at -40℃; for 1h; Molecular sieve; Inert atmosphere;	A 30% B 51%

benzyl 2,6-di-O-benzyl-β-D-galactopyranoside (73108-30-2) + N-acetyl-4,7,8,9-tetra-O-acetyl-2-chloro-2-deoxyneuraminic acid methyl ester (67670-69-3) → C46H53NO17 (113473-47-5) + benzyl O--(2-3)-2,6-di-O-benzyl-β-D-galactopyranoside (96520-15-9) + methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) + (2R,4S,5R,6R)-4-Acetoxy-5-acetylamino-2-((2R,3R,4S,5R,6R)-5,6-bis-benzyloxy-2-benzyloxymethyl-4-hydroxy-tetrahydro-pyran-3-yloxy)-6-((1S,2R)-1,2,3-triacetoxy-propyl)-tetrahydro-pyran-2-carboxylic acid methyl ester

Conditions	Yield
With 4 A molecular sieve; mercury(II) cyanide; mercury dibromide In dichloromethane at 20℃; for 48h; Further byproducts given;	A 1.6% B 11.6% C 49% D 8.4%

N-acetyl-4,7,8,9-tetra-O-acetyl-2-chloro-2-deoxyneuraminic acid methyl ester (67670-69-3) → C46H53NO17 (113473-47-5) + benzyl O--(2-3)-2,6-di-O-benzyl-β-D-galactopyranoside (96520-15-9) + methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) + (2R,4S,5R,6R)-4-Acetoxy-5-acetylamino-2-((2R,3R,4S,5R,6R)-5,6-bis-benzyloxy-2-benzyloxymethyl-4-hydroxy-tetrahydro-pyran-3-yloxy)-6-((1S,2R)-1,2,3-triacetoxy-propyl)-tetrahydro-pyran-2-carboxylic acid methyl ester

Conditions	Yield
With benzyl 2,6-di-O-benzyl-β-D-galactopyranoside; 4 A molecular sieve; mercury(II) cyanide; mercury dibromide In dichloromethane at 20℃; for 48h; Further byproducts given;	A 1.6% B 11.6% C 49% D 8.4%

benzyl 2,3,4-tri-O-benzyl-β-D-galactopyranoside (35017-04-0) + N-acetyl-4,7,8,9-tetra-O-acetyl-2-chloro-2-deoxyneuraminic acid methyl ester (67670-69-3) → methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) + Benzyl-2,3,4-tri-O-benzyl-6-O-(methyl-5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-didesoxy-D-glycero-α-D-galacto-2-nonulopyranosylonat)-β-D-galactopyranosid (82703-91-1) + Benzyl-2,3,4-tri-O-benzyl-6-O-(methyl-5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-didesoxy-β-D-glycero-D-galacto-2-nonulopyranosylonat)-β-D-galactopyranosid (89733-59-5)

Conditions	Yield
With mercury(II) cyanide; mercury dibromide In dichloromethane for 96h; Ambient temperature;	A n/a B 36% C 48%

methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) → methyl 5-acetamido-2,6-anhydro-3,5-dideoxy-D-glycero-D-galacto-non-2-enonate (25875-99-4, 79026-38-3)

Conditions	Yield
With methanol; sodium methylate Zemplen deacetylation;	100%
Stage #1: methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate With sodium methylate In methanol at 20℃; for 3h; Stage #2: In methanol	78%
With sodium methylate In methanol for 1.5h;

methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) → methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-2,3-dibromo-2,3,5-trideoxy-β-D-erythro-L-manno-non-2-ulopyranosonate (108999-04-8)

Conditions	Yield
With sodium bromide In water; acetonitrile electrochemical oxidation;	98%
With sodium bromide In water; acetonitrile at 20℃; for 2h; electrolyses;	98%
With bromine In dichloromethane at 0 - 20℃; for 0.5h; Inert atmosphere;	93%
With bromine In dichloromethane at 0℃; for 0.2h;
With bromine In dichloromethane at 0 - 20℃; Inert atmosphere;

methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) → methyl (3aS,4R,7aR)-4-[(1S,2R)-1,2,3-triacetoxy-propyl]-2-methyl-3a,7a-dihydro-4H-pyrano[3,4-d][1,3]oxazole-6-carboxylate (78850-37-0)

Conditions	Yield
With sulfuric acid; acetonitrile at 50℃; for 0.5h; diastereoselective reaction;	97%
With methanol; boron trifluoride diethyl etherate In dichloromethane at 25 - 30℃; for 16h;	96%
With boron trifluoride diethyl etherate In methanol; benzene for 18h; Ambient temperature;
Stage #1: methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate With sulfuric acid; acetic anhydride; acetic acid at 20℃; for 48h; Acetolysis; Stage #2: With water; sodium hydrogencarbonate for 2h; pH=9; Cyclization;
With sulfuric acid In acetonitrile at 50℃; for 0.5h;

di-tert-butyl dicarbonate (24424-99-5) + methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) → methyl 5-[acetyl(tert-butoxycarbonyl)amino]-4,7,8,9-tetra-O-acetyl-2,6-anhydro-3,5-dideoxy-D-glycero-D-galacto-non-2-enonate (334934-26-8)

Conditions	Yield
With dmap In tetrahydrofuran for 3h; Inert atmosphere; Reflux;	97%
With dmap In tetrahydrofuran for 4h; Reflux;	90%
With dmap In tetrahydrofuran for 14h;	89%
With dmap In tetrahydrofuran for 3h; Reflux;	77%
With dmap In tetrahydrofuran at 60℃; Inert atmosphere;	71%

methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) + cyclopentanone (120-92-3) → 1-C-[methyl(5-acetamido-7,8,9-tri-O-acetyl-2,6-anhydro-3,5-dideoxy-D-glycero-α-D-galactononulosyl)-3-enoate]cyclopentanol (1616503-12-8)

Conditions	Yield
With samarium diiodide In tetrahydrofuran at -78 - 20℃; for 1h; Barbier Coupling Reaction; Inert atmosphere; regioselective reaction;	97%

methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) → methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-2,6-anhydro-2,3-dibromo-3,5-dideoxy-D-rabino-L-talo-nononate (121363-81-3)

Conditions	Yield
With bromine In tetrachloromethane for 2h;	96%

methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) + cyclohexanone (108-94-1) → 1-C-[methyl(5-acetamido-7,8,9-tri-O-acetyl-2,6-anhydro-3,5-dideoxy-D-glycero-α-D-galactononulosyl)-3-enoate]cyclohexanol (1616503-11-7)

Conditions	Yield
With samarium diiodide In tetrahydrofuran at -78 - 20℃; for 1h; Barbier Coupling Reaction; Inert atmosphere; regioselective reaction;	96%

cyclobutanone (1191-95-3) + methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) → 1-C-[methyl(5-acetamido-7,8,9-tri-O-acetyl-2,6-anhydro-3,5-dideoxy-D-glycero-α-D-galactononulosyl)-3-enoate]cyclobutanol (1616503-13-9)

Conditions	Yield
With samarium diiodide In tetrahydrofuran at -78 - 20℃; for 1h; Barbier Coupling Reaction; Inert atmosphere; regioselective reaction;	96%

methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) + N-tert-butyloxycarbonylpiperidin-4-one (79099-07-3) → 4-C-[methyl(5-acetamido-7,8,9-tri-O-acetyl-2,6-anhydro-3,5-dideoxy-D-glycero-α-D-galactononulosyl)-3-enoate]-N-(tert-butoxycarbonyl)piperidin-4-ol (1616503-15-1)

Conditions	Yield
With samarium diiodide In tetrahydrofuran at -78 - 20℃; for 1h; Barbier Coupling Reaction; Inert atmosphere; regioselective reaction;	96%

methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) → 4,7,8,9-tetra-O-acetyl-2-deoxy-N-acetyl-β-neuraminic acid methyl ester (116296-69-6)

Conditions	Yield
With hydrogen; palladium on activated charcoal In isopropyl alcohol	95%

methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) + acetonitrile (75-05-8) → methyl (3aS,4R,7aR)-4-[(1S,2R)-1,2,3-triacetoxy-propyl]-2-methyl-3a,7a-dihydro-4H-pyrano[3,4-d][1,3]oxazole-6-carboxylate (78850-37-0)

Conditions	Yield
With sulfuric acid In acetonitrile at 80℃; for 0.0833333h; Ritter Amidation; stereoselective reaction;	95%

methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) → C20H28BrNO13

Conditions	Yield
With N-Bromosuccinimide In water; acetonitrile at 80℃; for 2h;	94%

methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) + acetone (67-64-1) → 2-C-[methyl(5-acetamido-7,8,9-tri-O-acetyl-2,6-anhydro-3,5-dideoxy-D-glycero-α-D-galactononulosyl)-3-enoate]propan-2-ol (1616503-16-2)

Conditions	Yield
With samarium diiodide In tetrahydrofuran at -78 - 20℃; for 1h; Barbier Coupling Reaction; Inert atmosphere; regioselective reaction;	92%

methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) + butanone (78-93-3) → 2-C-[methyl(5-acetamido-7,8,9-tri-O-acetyl-2,6-anhydro-3,5-dideoxy-D-glycero-α-D-galacto-nonulosyl)-3-enoate]butan-2-ol (1616503-17-3)

Conditions	Yield
With samarium diiodide In tetrahydrofuran at -78 - 20℃; for 1h; Barbier Coupling Reaction; Inert atmosphere; regioselective reaction;	91%

Isopropenyl acetate (108-22-5) + methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) → methyl 4,7,8,9-tetra-O-acetyl-5-(N,N-diacetylamino)-3,5-dideoxy-2,6-anhydro-D-glycero-D-galacto-non-2-enonate

Conditions	Yield
With toluene-4-sulfonic acid at 65℃; for 16h;	90%

methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) + 4-tercbutyl-cyclohexanone (98-53-3) → 1-C-[methyl(5-acetamido-7,8,9-tri-O-acetyl-2,6-anhydro-3,5-dideoxy-D-glycero-α-D-galactononulosyl)-3-enoate]-4-tert-butylcyclohexanol

Conditions	Yield
With samarium diiodide In tetrahydrofuran at -78 - 20℃; for 1h; Barbier Coupling Reaction; Inert atmosphere; regioselective reaction;	88%

2,4-dimethylbenzenesulphenyl chloride (74880-42-5) + methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) → (2S,3R,4R,5S,6R)-4-Acetoxy-5-acetylamino-2-chloro-3-(2,4-dimethyl-phenylsulfanyl)-6-((1S,2R)-1,2,3-triacetoxy-propyl)-tetrahydro-pyran-2-carboxylic acid methyl ester + (2S,3S,4R,5S,6R)-4-Acetoxy-5-acetylamino-2-chloro-3-(2,4-dimethyl-phenylsulfanyl)-6-((1S,2R)-1,2,3-triacetoxy-propyl)-tetrahydro-pyran-2-carboxylic acid methyl ester

Conditions	Yield
In dichloromethane at 0℃; for 336h; Yield given;	A n/a B 85%
In dichloromethane at 0℃; for 336h; Yields of byproduct given;	A n/a B 85%

methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate (73960-72-2) → 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (24967-27-9, 79026-37-2, 108675-60-1, 108675-61-2, 108675-62-3) + 5-amino-2,6-anhydro-3,5-dideoxy-D-glycero-D-galacto-non-2-enonic acid (41976-42-5)

Conditions	Yield
With barium dihydroxide; water at 90℃; for 18h; Hydrolysis;	A n/a B 85%

Upstream product

• 35017-04-0 benzyl 2,3,4-tri-O-benzyl-β-D-galactopyranoside 
• 67670-69-3 N-acetyl-4,7,8,9-tetra-O-acetyl-2-chloro-2-deoxyneuraminic acid methyl ester 
• 140-89-6 potassium ethyl xanthogenate 
• 108740-39-2 (1S,2R)-1-((2R,3R,4S,6R)-3-acetamido-4,6-diacetoxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)propane-1,2,3-triyl triacetate 
• 88773-80-2 cyclohexylmethyl trimethylsilyl ether 
• 155155-64-9 (4S,5R,6R)-4-Acetoxy-5-acetylamino-2-phenylsulfanyl-6-((1S,2R)-1,2,3-triacetoxy-propyl)-tetrahydro-pyran-2-carboxylic acid methyl ester 
• 390400-39-2 C₅₀H₅₇NO₁₅ 
• 53008-65-4 methyl 2,3,4-tri-O-benzyl-D-glucopyranoside 
• 118977-25-6 methyl (phenyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycerol-β-D-galactonon-2-ulopyranoside)onate 
• 4304-12-5 benzyl β-D-galactopyranoside 
• 10387-40-3 potassium thioacetate 
• 20298-35-5 N-acetylneuraminic acid methyl ester 
• 108-24-7 acetic anhydride 
• 72718-62-8 2,3-di-O-acetyl-β-D-glucopyranosyl-(1->4)-1,2,3,6-tetra-O-acetyl-β-D-glucopyranose 

Downstream Products

• 24967-27-9 2,3-dehydro-2-deoxy-N-acetylneuraminic acid 
• 25875-99-4 methyl 5-acetamido-2,6-anhydro-3,5-dideoxy-D-glycero-D-galacto-non-2-enonate 
• 41976-42-5 5-amino-2,6-anhydro-3,5-dideoxy-D-glycero-D-galacto-non-2-enonic acid 
• 347838-02-2 methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-3-phenylseleno-D-erythro-α-L-gluco-2-nonulopyranosonate 
• 1304780-01-5 methyl 5-acetamido-2,6-anhydro-3,5-dideoxy-8,9-O-isopropylidene-4-O-[3-(phenylamino)-3-(methylsulfonylimino)propoxy]-D-glycero-D-galacto-non-2-enonate 
• 1304780-02-6 methyl 5-acetamido-2,6-anhydro-3,5-dideoxy-8,9-O-isopropylidene-4-O-[3-(diethylamino)-3-(4-methylbenzenesulfonylimino)propoxy]-D-glycero-D-galacto-non-2-enonate 
• 1304780-03-7 methyl 5-acetamido-2,6-anhydro-3,5-dideoxy-8,9-O-isopropylidene-4-O-[3-(diisopropylamino)-3-(4-methylbenzenesulfonylimino)propoxy]-D-glycero-D-galacto-non-2-enonate 
• 1304780-04-8 methyl 5-acetamido-2,6-anhydro-3,5-dideoxy-8,9-O-isopropylidene-4-O-[3-(isopropylamino)-3-(4-methylbenzenesulfonylimino)propoxy]-D-glycero-D-galacto-non-2-enonate 
• 1304780-07-1 5-acetamido-2,6-anhydro-3,5-dideoxy-4-O-[3-(phenylamino)-3-(methanesulfonylimino)propoxy]-D-glycero-D-galacto-non-2-enonic acid 
• 1304780-08-2 5-acetamido-2,6-anhydro-3,5-dideoxy-4-O-[3-(diethylamino)-3-(tosylimino)propoxy]-D-glycero-D-galacto-non-2-enonic acid 
• 1304780-09-3 5-acetamido-2,6-anhydro-3,5-dideoxy-4-O-[3-(diisopropylamino)-3-(tosylimino)propoxy]-D-glycero-D-galacto-non-2-enonic acid 
• 1304780-10-6 5-acetamido-2,6-anhydro-3,5-dideoxy-4-O-[3-(diisopropylamino)-3-(tosylimino)-propoxy]-D-glycero-D-galacto-non-2-enonic acid 

Relevant articles and documents

Functionalization of 2-Deoxy-2,3-dehydro-N-acetylneuraminic Acid Methyl Ester

The acetyl protected 2-deoxy-2,3-dehydroneuraminic acid methyl ester was functionalized by modifying its 2,3-double bond to convert it into new glycosyl donors such as 2,3-dibromo-, 2,3-epoxy-, and 2-halo-3-hydroxyneuraminic acid derivatives.

Selective synthesis of Neu5Ac2en and its oxazoline derivative using BF3·Et2O

Application of the Lewis acid BF3·Et2O to the selective synthesis of 5-acetamido-2,6-anhydro-3,5-dideoxy-d-glycero-d-galacto-non-2-enonic acid (Neu5Ac2en) and the related oxazoline, methyl 7,8,9-tri-O-acetyl-2,3,4,5-tetradeoxy-2,3-didehydro-2,3-trideoxy-4′,5′-dihydro-2′-methyloxazolo[5,4-d]- d-glycero-d-talo-non-2-enonate is described.

A facile synthesis of 2-deoxy-2,3-didehydroneuraminic acid derivatives

The 2-thio- or 2-selenoglycosides of N-acetylneuraminic acid methyl ester were transformed by successive treatment with dimethyl(methylthio)sulfonium triflate (DMTST) and 1,8-diazabicyclo[5.4.0]-7- undecene (DBU) to give the corresponding methyl 2-deoxy-2,3- didehydroneuraminates in excellent yields. Their acids and their analogues are sialidase inhibitors of pharmaceutical interest.

Efficient method for the preparation of peracetylated Neu5Ac2en by flash vacuum pyrolysis

Peracetylated Neu5Ac2en methyl ester, an intermediate in the synthesis of the influenza neuraminidase inhibitor Relenza, has been synthesized in high yields from peracetylated Neu5Ac methyl ester by flash vacuum pyrolysis. Mechanistic evidence including deuterium labeled studies and DFT (B3LYP) calculations suggest this transformation proceeds via an intramolecular syn-elimination.

Donor-Reactivity-Controlled Sialylation Reactions

Although tremendous efforts have been made for the efficient preparation of sialosides, controlling the stereochemical outcome of sialylation reaction still remains one of the most challenging tasks due to the unique chemical structure of sialic acid. We developed a new strategy to statistically analyze the stereoselectivity of sialylation reactions on six types of p-tolyl thiosialosides in NIS/TfOH system using Relative Reactivity Value (RRV) as the indicator. Analysis of the reaction mechanism showed the formation of the relatively stable glycosyl bromide and glycosyl chloride intermediates from halide- and triflate-containing promotors in the absence of an acceptor. We found that the α/β-stereoselectivity, yields, and intermediate changes were associated with their donor reactivity. These findings enable to tailor the most suitable building blocks for stereo-controlled sialylation reactions.

One pot synthesis of thio -glycosides via aziridine opening reactions

A one-pot aziridine opening reaction by glycosyl thiols generated in situ from the corresponding anomeric thio-acetates affords thio-glycosides with a pseudo-disaccharide structure and an N-linked tether. The scope of the one-pot aziridine opening reaction was explored on a series of mono- and disaccharides, creating a class of pseudo-glycosidic compounds with potential for further functionalization. Unexpected anomerization of glycosyl thiols was observed under the reaction conditions and the influence of temperature, base and solvent on the isomerization was investigated. Single isomers were obtained in good to acceptable yields for mannose, rhamnose and sialic acid derivatives. The class of thio-glycomimetics synthesized can potentially be recognized by various lectins, while presenting hydrolytic and enzymatic stability. The nitrogen functionality incorporated in the glycomimetics can be exploited for further functionalization, including tethering to linkers, scaffolds or peptide residues.