76801-85-9

Usage

Uses

Used in Pharmaceutical Industry:
Azathramycin is used as an intermediate in the production of Azithromycin, a widely prescribed antibiotic. It is utilized for its antibiotic properties to treat various bacterial infections, including respiratory, skin, and ear infections.
Used in Research and Development:
In the field of scientific research, Azathramycin serves as a valuable compound for studying the structure and function of Azithromycin and its derivatives. This helps in the development of new antibiotics and understanding the mechanisms of action against bacterial pathogens.
Used in Quality Control:
Azathramycin is also used in the quality control processes of pharmaceutical companies to ensure the purity and potency of Azithromycin products. It helps in the identification and quantification of impurities, which is crucial for maintaining the safety and efficacy of the final drug product.

InChI:InChI=1/C37H70N2O12/c1-14-26-37(10,45)30(41)23(6)38-18-19(2)16-35(8,44)32(51-34-28(40)25(39(11)12)15-20(3)47-34)21(4)29(22(5)33(43)49-26)50-27-17-36(9,46-13)31(42)24(7)48-27/h19-32,34,38,40-42,44-45H,14-18H2,1-13H3

Synthetic route

9-deoxo-6-deoxy-6,9-epoxy-9,9a-didehydro-9a-aza-homoerythromycin A (342371-84-0) → 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9)

Conditions	Yield
With potassium borohydride In methanol at 0 - 5℃; for 2h;	93%
Stage #1: 9-deoxo-6-deoxy-6,9-epoxy-9,9a-didehydro-9a-aza-homoerythromycin A With hydrogen; acetic acid; platinum(IV) oxide In methanol at 40 - 45℃; pH=5 - 6; Stage #2: With sodium hydroxide In water pH=11 - 12;	85%
Stage #1: 9-deoxo-6-deoxy-6,9-epoxy-9,9a-didehydro-9a-aza-homoerythromycin A With sodium tetrahydroborate; acetic acid pH=6 - 8; Heating; Stage #2: With gluconic acid at 8℃; Reagent/catalyst; Temperature;	84.4%
With sodium tetrahydroborate In methanol at 0 - 25℃; Inert atmosphere;	77%
With methanol; sodium tetrahydroborate at 0 - 20℃; for 24h;	70.3%

C37H66N2O12 → 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9)

Conditions	Yield
Stage #1: C37H66N2O12 With perchloric acid; hydrogen; platinum on activated charcoal In methanol at 5 - 42℃; under 10298 Torr; for 3h; pH=5.5; Stage #2: With sodium hydroxide In water pH=12 - 12.5;	91.5%

C37H66N2O12 → 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9)

Conditions	Yield
Stage #1: C37H66N2O12 With perchloric acid; hydrogen; platinum on activated charcoal In methanol; water at 5 - 42℃; under 10298 Torr; for 3h; pH=5.5; Stage #2: With sodium hydroxide In water pH=12 - 12.5; Product distribution / selectivity;	86.6%

C37H66N2O12 → 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9)

Conditions	Yield
Stage #1: C37H66N2O12 With potassium borohydride; acetic acid In water at 14℃; under 22502.3 Torr; pH=7; Flow reactor; Stage #2: In ethyl acetate Stage #3: With hydrogenchloride In water; ethyl acetate for 0.05h; Pressure; Temperature; pH-value; Solvent;	86%

(9-E)-deoxo-9-hydroximinoerythromycin A (13127-18-9) → 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9)

Conditions	Yield
Stage #1: (9-E)-deoxo-9-hydroximinoerythromycin A With calcium(II) bis(trifluoromethanesulfonyl)imide; tert-butylammonium hexafluorophosphate(V) In 1,2-dimethoxyethane; 1,2-dichloro-ethane at 80℃; for 5h; Stage #2: With sodium tetrahydroborate In methanol at 0 - 20℃; for 51h;	78%
Multi-step reaction with 2 steps 1: p-toluenesulfonyl chloride; sodium hydrogencarbonate / acetone; water / 4 h / 0 - 20 °C 2: sodium tetrahydroborate; methanol / 24 h / 0 - 20 °C View Scheme

erythromycin A 9-(E)-oxime (111321-02-9) → 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9)

Conditions	Yield
Rearrangement; Beckmann-like rearrangement; reduction;	45%
Stage #1: erythromycin A 9-(E)-oxime With sodium hydrogencarbonate; p-toluenesulfonyl chloride In acetone Beckmann rearrangement; Stage #2: With hydrogen; platinum on activated charcoal In methanol under 30003 Torr; for 12h; Further stages.;
Multi-step reaction with 2 steps 1: methanol; water / 5 h / 5 °C / Inert atmosphere 2: sodium tetrahydroborate / methanol / 4 - 20 °C / Inert atmosphere View Scheme

erythromycin 6,9-imino ether → 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9)

Conditions	Yield
With platinum on carbon; hydrogen In methanol at 40 - 45℃; under 7500.75 Torr; for 4h; Autoclave;	17.1%

C70H128BN4O26(1-)*Na(1+) → 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9)

Conditions	Yield
With Amberlite IRA-743; sulfuric acid; water for 0.5h; pH=2.8;

C38H70N2O12 (944124-75-8) → 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9)

Conditions	Yield
Stage #1: C38H70N2O12 With sodium tetrahydroborate; formic acid In water at 0 - 20℃; for 11h; pH=6 - 8; Stage #2: With malic acid In water Stage #3: With hydrogenchloride; sodium hydroxide more than 3 stages;

C44H74N2O15S (227948-37-0) → 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9)

Conditions	Yield
With sodium tetrahydroborate In methanol at 4 - 20℃; Beckmann rearrangement; Inert atmosphere;	300 mg

erythromycin (114-07-8) → 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: hydroxylamine; acetic acid / water; isopropyl alcohol / 15 h / 50 °C / Inert atmosphere 2: methanol; water / 5 h / 5 °C / Inert atmosphere 3: sodium tetrahydroborate / methanol / 4 - 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: hydroxylamine hydrochloride; triethylamine / methanol / 24 h / Reflux 2: p-toluenesulfonyl chloride; sodium hydrogencarbonate / acetone; water / 4 h / 0 - 20 °C 3: sodium tetrahydroborate; methanol / 24 h / 0 - 20 °C View Scheme

erythromycin A oxime thiocyanate (1357466-70-6) → 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9)

Conditions	Yield
Stage #1: erythromycin A oxime thiocyanate With sodium hydroxide In dichloromethane at 10℃; pH=9 - 11; Stage #2: With sodium tetrahydroborate In dichloromethane at 10℃; pH=0.5 - 2.5;	57.4 g
Multi-step reaction with 2 steps 1.1: sodium hydrogencarbonate; p-toluenesulfonyl chloride / acetone / 4 h / 0 - 10 °C 2.1: phosphoric acid; potassium borohydride / water / 8 h / 0 - 5 °C / pH 7 - 9 2.2: 3 h / 0 - 5 °C / pH 2.5 - 3 View Scheme
Multi-step reaction with 3 steps 1.1: sodium hydroxide / dichloromethane; water / 38 °C 2.1: sodium carbonate; p-toluenesulfonyl chloride / water / 3.2 h / 12 °C / pH Ca. 7 3.1: acetic acid; potassium borohydride / water / 14 °C / 22502.3 Torr / pH 7 / Flow reactor 3.3: 0.05 h View Scheme

erythromycin A thiocyanate (7704-67-8) → 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: hydroxylamine hydrochloride; triethylamine / methanol / 52 h / 30 - 55 °C / pH 6.3 - 6.7 2.1: sodium hydrogencarbonate; p-toluenesulfonyl chloride / acetone / 4 h / 0 - 10 °C 3.1: phosphoric acid; potassium borohydride / water / 8 h / 0 - 5 °C / pH 7 - 9 3.2: 3 h / 0 - 5 °C / pH 2.5 - 3 View Scheme

erythromycin A 6,9-imino ether → 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9)

Conditions	Yield
Stage #1: erythromycin A 6,9-imino ether With potassium borohydride; phosphoric acid In water at 0 - 5℃; for 8h; pH=7 - 9; Stage #2: With hydrogenchloride In dichloromethane; water at 0 - 5℃; for 3h; pH=2.5 - 3; Reagent/catalyst;

benzyl chloroformate (501-53-1) + 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9) → (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)oxy]-2-ethyl-3,4,10-trihydroxy-3,5,8,10,12,14-hexamethyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-2-O-[(phenylmethoxy)carbonyl]-β-D-xylo-hexopyranosyl]oxy]-1-oxa-6-azacyclopentadecan-15-one (352032-78-1)

Conditions	Yield
In dichloromethane at 0℃;	100%
Stage #1: benzyl chloroformate; 9-Deoxo-9a-aza-9a-homoerythromycin A In dichloromethane at -10 - 3℃; for 0.166667h; Stage #2: With triethylamine In dichloromethane at 3℃; for 2h;	96.9%
In dichloromethane at 0 - 5℃; for 1h;	84.57%

acrylonitrile (107-13-1) + 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9) → 9-deoxo-9a-aza-9a-(β-cyanoethyl)-9a-homoerythromycin A (92627-70-8)

Conditions	Yield
at 80℃; for 24h; Michael addition;	99%
at 60℃; for 16h; Inert atmosphere;	63%
for 7h; Heating / reflux;	41%

formaldehyd (50-00-0) + 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9) → Zithromax(R) (83905-01-5, 92470-27-4)

Conditions	Yield
With formic acid In acetone at 30 - 55℃; for 4h;	95%
Stage #1: formaldehyd; 9-Deoxo-9a-aza-9a-homoerythromycin A With formic acid In acetone at 40 - 45℃; for 7 - 8h; Stage #2: With sodium hydroxide In water; acetone pH=11 - 11.5;	87%
With formic acid In water; ethyl acetate for 2h; Heating / reflux;	77%

9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9) → 9-deoxo-9-dihydro-3'-N-oxide-9a-aza-9a-homoerythromycin A

Conditions	Yield
With dihydrogen peroxide In methanol; water at 0 - 20℃; for 2h;	94.3%
With dihydrogen peroxide In methanol; water at 0 - 20℃; for 2h;	94.3%

Benzyl isothiocyanate (622-78-6) + 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9) → C45H77N3O12S (166036-09-5)

Conditions	Yield
With triethylamine In acetonitrile at 60℃; for 3h;	92%

phenyl chloroformate (1885-14-9) + 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9) → C44H74N2O14

Conditions	Yield
In dichloromethane at -5 - 0℃; for 3h;	92%

formaldehyd (50-00-0) + 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9) → azithromycin dihydrate

Conditions	Yield
Stage #1: formaldehyd; 9-Deoxo-9a-aza-9a-homoerythromycin A With formic acid In acetone at 40 - 45℃; for 7 - 8h; Stage #2: With sodium hydroxide In water; acetone pH=11 - 11.5; Stage #3: With water In acetone at 20℃; for 24h;	87%
Stage #1: formaldehyd; 9-Deoxo-9a-aza-9a-homoerythromycin A With formic acid In water; acetone at 20 - 55℃; for 8h; Stage #2: With water In acetone at 38 - 40℃; for 10 - 12h; Stage #3: With water	76.7%
Stage #1: formaldehyd; 9-Deoxo-9a-aza-9a-homoerythromycin A With formic acid In chloroform; water at 20 - 55℃; for 10 - 20h; Heating / reflux; Stage #2: With water In acetone at 38 - 40℃; for 10 - 12h;	73%

di-tert-butyl dicarbonate (24424-99-5) + 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9) → (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-((2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)oxy)-2-ethyl-3,4,10-trihydroxy-3,5,8,10,12,14-hexamethyl-11-((3,4,6-trideoxy-3-(dimethylamino)-2-O-(tert-butoxycarbonyl)-β-D-xylo-hexopyranosyl)oxy)-1-oxa-6-(tert-butoxycarbonyl)azacyclopentadecan-15-one

Conditions	Yield
With dmap In tetrahydrofuran at -5 - 5℃; for 10.5h; Solvent; Reflux;	86.3%

acrylic acid methyl ester (292638-85-8) + 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9) → 9-deoxo-9a-aza-9a-(γ-hydroxypropyl)-9a-homoerythromycin A (96779-85-0)

Conditions	Yield
Stage #1: acrylic acid methyl ester; 9-Deoxo-9a-aza-9a-homoerythromycin A at 60℃; for 30h; Addition; hetero-Michael addition; Stage #2: With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; for 1h; Reduction;	84%

9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9) → 3-O-decladinosyl-9-deoxo-9a-aza-9a-homoerythromycin A (111247-94-0)

Conditions	Yield
With hydrogenchloride at 20℃; for 24h; pH=1;	79%
Stage #1: 9-Deoxo-9a-aza-9a-homoerythromycin A With formaldehyd; formic acid In water for 30h; Reflux; Stage #2: With sodium hydroxide In water pH=11;	61%
With hydrogenchloride at 20℃; for 12h;

acrylic acid methyl ester (292638-85-8) + 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9) → 3-(9-deoxo-9-dihydro-9a-aza-9a-homoerythromycin A) propionic acid methyl ester (955955-02-9)

Conditions	Yield
In chloroform at 60℃; for 48h;	65%
In chloroform at 60℃; for 48h; Heating / reflux;	53.7%

9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9) → (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-2-ethyl-3,4,10,11,13-pentahydroxy-3,5,8,10,12,14-hexamethyl-15-oxo-1-oxa-6-azacyclopentadecan-15-one (111247-95-1)

Conditions	Yield
With hydrogenchloride In water at 50℃; for 10h;	60.1%
With hydrogenchloride In water at 60℃; for 64h;

imidazole-1-carboxylic acid [2-(tert-butyl-dimethyl-silanyloxymethyl)-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yl]-amide (287727-89-3) + 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9) → 9a-aza-9a-[(3'-deoxythymidin-3'-yl)aminocarbonyl]-9-deoxo-9a-homoerythromycin A

Conditions	Yield
Stage #1: imidazole-1-carboxylic acid [2-(tert-butyl-dimethyl-silanyloxymethyl)-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yl]-amide; 9-Deoxo-9a-aza-9a-homoerythromycin A In N,N-dimethyl-formamide; acetonitrile at 50℃; for 2h; Acylation; Stage #2: With pyridine; hydrogen fluoride In tetrahydrofuran at 0℃; Decomposition;	50%

(11-carboxyundecyl)triphenylphosphonium bromide (7530-96-3) + 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9) → {11-[(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-11-{[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy}-2-ethyl-3,4,10-trihydroxy-13-{[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy}-3,5,8,10,12,14-hexamethyl-15-oxo-1-oxa-6-azacyclopentadecan-6-yl]-11-oxoundecyl}triphenylphosphonium chloride

Conditions	Yield
Stage #1: (11-carboxyundecyl)triphenylphosphonium bromide With 1-hydroxy-7-aza-benzotriazole; N-ethyl-N,N-diisopropylamine; diisopropyl-carbodiimide In dichloromethane at 40℃; for 0.5h; Stage #2: 9-Deoxo-9a-aza-9a-homoerythromycin A In dichloromethane at 40℃; Stage #3: In methanol	49%
Stage #1: (11-carboxyundecyl)triphenylphosphonium bromide With 1-hydroxy-7-aza-benzotriazole; N-ethyl-N,N-diisopropylamine; diisopropyl-carbodiimide In dichloromethane at 40℃; for 0.5h; Stage #2: 9-Deoxo-9a-aza-9a-homoerythromycin A In dichloromethane at 40℃; Stage #3: In methanol	0.4 g

ethyl isocyanate (109-90-0) + 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9) → C40H75N3O13 (1289429-77-1)

Conditions	Yield
In toluene at 20℃; for 1h; Inert atmosphere;	47%

3-methoxybiphenyl-4-yl isothiocyanate (1304028-65-6) + 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9) → 9a,11-O-{N'-[4-(3-methoxy)biphenyl]carbonimidoyl}-9-deoxo-9a-aza-9a-homoerythromycin A

Conditions	Yield
With triethylamine In acetonitrile at 60℃;	41%

isopropyl isothiocyanate (2253-73-8) + 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9) → 9a,11-O-(N'-isopropropylcarbonimidoyl)-9-deoxo-9a-aza-9a-homoerythromycin A

Conditions	Yield
With triethylamine In acetonitrile at 60℃;	39%

benzyl isothiocyanate (3173-56-6) + 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9) → C45H77N3O13 (166036-08-4)

Conditions	Yield
In toluene Inert atmosphere;	35%

Allyl acetate (591-87-7) + 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9) → C40H74N2O12 (119471-59-9)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); triethylamine at 20 - 80℃; for 22h; Inert atmosphere;	26%

propionaldehyde (123-38-6) + 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9) → n-propyl azithromycin (92594-48-4)

Conditions	Yield
With sodium cyanoborohydride; acetic acid In N,N-dimethyl-formamide at 70℃; for 7h; Inert atmosphere;	24%
With 5%-palladium/activated carbon; hydrogen In ethanol at 35 - 45℃; under 750.075 - 4500.45 Torr; for 4h; Temperature; Pressure; Solvent; Reagent/catalyst; Autoclave;

benzaldehyde (100-52-7) + 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9) → C44H76N2O12 (119471-61-3)

Conditions	Yield
With sodium cyanoborohydride; acetic acid In N,N-dimethyl-formamide Inert atmosphere;	21%

9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9) + cyclohexanecarbaldehyde (2043-61-0) → C44H82N2O12 (1289430-07-4)

Conditions	Yield
With sodium cyanoborohydride; acetic acid In N,N-dimethyl-formamide Inert atmosphere;	21%

4-Ethynylbenzaldehyde (63697-96-1) + 9-Deoxo-9a-aza-9a-homoerythromycin A (76801-85-9) → (N10-(4-ethynylbenzyl))azithromycin

Conditions	Yield
Stage #1: 4-Ethynylbenzaldehyde; 9-Deoxo-9a-aza-9a-homoerythromycin A With acetic acid In N,N-dimethyl-formamide for 0.5h; Stage #2: With sodium cyanoborohydride In N,N-dimethyl-formamide at 70℃; for 7h;	20%

Upstream product

• 111321-02-9 erythromycin A 9-(E)-oxime 
• 944124-75-8 C₃₈H₇₀N₂O₁₂ 
• 227948-37-0 C₄₄H₇₄N₂O₁₅S 
• 114-07-8 erythromycin 
• 13127-18-9 (9-E)-deoxo-9-hydroximinoerythromycin A 
• 7704-67-8 erythromycin thiocyanate A 
• 1357466-70-6 erythromycin A oxime thiocyanate 
• 342371-84-0 9-deoxo-6-deoxy-6,9-epoxy-9,9a-didehydro-9a-aza-homoerythromycin A 
• 13127-18-9 erythromycin A oxime 
• 111247-90-6 C₄₅H₇₅N₃O₁₆S*ClH 
• 99290-97-8 C₃₇H₆₆N₂O₁₂ 

Downstream Products

• 352032-78-1 (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)oxy]-2-ethyl-3,4,10-trihydroxy-3,5,8,10,12,14-hexamethyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-2-O-[(phenylmethoxy)carbonyl]-β-D-xylo-hexopyranosyl]oxy]-1-oxa-6-azacyclopentadecan-15-one 
• 690258-30-1 9-deoxo-9-dihydro-9a-N-{[4-(chlorosulfonyl)phenyl]-carbamoyl}-9a-aza-9a-homoerithromycin A 
• 690258-31-2 9-deoxo-9-dihydro-9a-N-{[4-(chlorosulfonyl)phenyl]-carbamoyl}-9a-aza-9a-homoerithronolide A 
• 690258-32-3 9-deoxo-9a-{N'-[4-(aminosulfonyl)phenyl]carbamoyl}-9a-aza-9a-homoerythromycin 
• 690258-33-4 9-deoxo-9a-{N'-[4-(phenylaminosulfonyl)phenyl]carbamoyl}-9a-aza-9a-homoerythromycin 
• 371193-61-2 carbonic acid benzyl ester 4-dimethylamino-2-[2-ethyl-3,4,10-trihydroxy-13-(4-methoxy-4,6-dimethyl-5-oxo-tetrahydro-pyran-2-yloxy)-3,5,8,10,12,14-hexamethyl-15-oxo-1-oxa-6-aza-cyclopentadec-11-yloxy]-6-methyl-tetrahydro-pyran-3-yl ester 

Relevant academic research and scientific papers

Method for synthesizing azorithromycin by utilizing erythromycin thiocyanate oxime

The invention relates to a method for synthesizing azithromycin by utilizing erythromycin thiocyanate oxime. The method comprises the following process steps: removing thiocyanate radicals through erythromycin thiocyanate oxime dissociation, performing rearrangement reaction, performing continuous back extraction, performing continuous reduction reaction and separation, and performing azithromycin crystallizing. According to the invention, the thiocyanate radicals are removed before the rearrangement reaction and then the rearrangement is performed, the reduction reaction adopts a continuous reaction process, the reaction mode is changed, and the process is high in reaction efficiency, low in production cost, small in environmental pollution, high in product yield and good in product quality.

Chemical synthesis method for azithromycin intermediate

The invention relates to a chemical synthesis method for an azithromycin intermediate. According to the chemical synthesis method for the azithromycin intermediate,erythromycin 6,9-imino ether is usedas a raw material and reduced by potassium borohydride and zinc trifluoromethanesulfonate, hydrolysis is assisted through IR.A-743 or ZXC-700 resin, and 9-deoxo-9-alpha-aza-9[alpha]-homoerythromycinA is obtained with a high yield.

Novel crystal-form compound of dihydroerythromycin and preparation method thereof

The invention relates to a novel crystal-form compound of dihydroerythromycin and a preparation method thereof, and belongs to the technical field of synthesis of heterocyclic compounds. Erythromycinimide ether is dissolved in methanol, a catalyst Pt/C is added after acid adjustment, and a hydrogenation reaction is performed; after the reaction is finished, the catalyst is filtered, and a set amount of methanol is recovered; the temperature is dropped and the alkalinity is adjusted to the pH value of 10-12, a set amount of water is added drop by drop, and the novel crystal-form compound of dihydroerythromycin is obtained by filtration and drying. The preparation method is applied in synthesis of dihydroerythromycin and has the advantages of good fluidity, easy packaging, high liquid content and the like.

Mild, calcium catalysed Beckmann rearrangements

A mild calcium catalysed Beckmann rearrangement has been realised, which forgoes the more traditional harsh reactions conditions associated with the transformation. The catalyst system is shown to be tolerant towards a wide variety of functional groups relevant to natural product synthesis and medicinal chemistry and the synthetic utility of the reaction has also been investigated. A preliminary mechanistic investigation was performed to understand the nature of the incoming nucleophile and a possible reaction pathway is described.

Macrolide derivative and application thereof

The invention provides a macrolide derivative of a novel structure. Experiments show that the macrolide derivative has a good promoting effect on alimentary motility and is capable of enhancing intestine peristalsis, increasing defecation quantity and accelerating passing of intestinal content; on such basis, it is further discovered that the macrolide derivative is low in antibiotic activity and small in side effect and can be taken as a gastrointestinal motility promoting drug. Particularly, a compound III-3 screened with the optimal efficacy is subjected to further efficacy evaluation as well as acute toxicity and cardiotoxicity evaluation by domestic rabbits, beagles and marmosets. Experiments show that the compound III-3 is safe and capable of effectively promoting gastrointestinal motility, thereby being excellent in druggability.

Synthesis method of azithromycin

The invention relates to a synthesis method of azithromycin. The synthesis method is characterized by comprising the process steps of firstly adding sodium bicarbonate and a rearrangement reaction reagent to erythromycin oxime in a reaction system employing water as a reaction solvent for rearrangement reaction, carrying out heat preservation for 2-3 hours, dropwise adding a reduction reaction regent for reduction reaction and stirring for 1-2 hours during heat preservation; adding a competitive inhibitor for removing boron through reduction hydrolysis for reduction and boron removal reaction; and finally separating out crystal, and cooling and filtering to obtain the azithromycin. Rearrangement and reduction are simultaneously carried out in the same reaction system. Compared with a sodium borohydride reduction method in the prior art, the synthesis method has the advantages that the process is simplified, use of an organic solvent and the like is omitted, the environmental pollution and the product cost are reduced, the influence of a complicated process on the quality of a product is reduced, the quality and the yield of the product are finally improved and the synthesis method is suitable for technological production.

Preparation method of norazithromycin

The invention discloses a preparation method of norazithromycin and relates to the technical field of macrolide antibiotics. The preparation method comprises the following steps: reducing erythrocin A 6,9-imino ether in water at 0 DEG C to room temperature under the pH of 7.0-9.0 by using a reducing agent sodium borohydride or potassium borohydride; then in the presence of an organic solvent and water, performing continuous hydrolysis at 0 DEG C to room temperature under the pH of 2.0-3.0; then adding two-phase reaction liquids after continuous hydrolysis into an alkaline aqueous solution, adjusting the pH to be greater than or equal to 12, stirring, layering and abandoning the aqueous phase, wherein the organic solvent is dichloromethane, chloroform, 1,2-dichloromethane, ethyl acetate or butyl acetate; and after the last hydrolysis reaction in continuous hydrolysis, performing layering, directly adding the aqueous phase into the alkaline aqueous solution, adjusting the pH to be greater than or equal to 12, and performing stirring and separating out norazithromycin. The method increases the utilization ratio of the reducing agent, can control reverse reactions of borate, and reduces unnecessary separating process to obtain high quality norazithromycin.

Dihydrokainate high method for preparing ycin (by machine translation)

The invention provides a method for the preparation of erythromycin the hydrogen is high, including, the boiling method: the erythromycin A9-oxime, water and rearrangement reagent for a BECKMANN rearrangement, reaction end, adjusting with alkali liquor pH3.0-7.0, by adding reducing agent to reducing, by acid hydrolysis, crystallization get dihydrokainate high ycin. The invention uses water as solvent the BECKMANN rearrangement and reduction reaction to boiling, is greatly shortened from the erythromycin A9-oxime or erythromycin A9- [...] cyanate to dihydrokainate high production of time, have reduced the process, at the same time reduces the three waste emissions, improved than that of the prior process yield 1-3%, further reduce the cost of production of Azithromycin. Without extracting erythromycin intermediate A6,9 imines ether, mild reaction conditions; water as a reaction solvent, there are few three wastes, green. (by machine translation)

Chemistry and biology of macrolide antiparasitic agents

Macrolide antibacterial agents inhibit parasite proliferation by targeting the apicoplast ribosome. Motivated by the long-term goal of identifying antiparasitic macrolides that lack antibacterial activity, we have systematically analyzed the structure-activity relationships among erythromycin analogues and have also investigated the mechanism of action of selected compounds. Two lead compounds, N-benzylazithromycin (11) and N-phenylpropylazithromycin (30), were identified with significantly higher antiparasitic activity and lower antibacterial activity than erythromycin or azithromycin. Molecular modeling based on the cocrystal structure of azithromycin bound to the bacterial ribosome suggested that a substituent at the N-9 position of desmethylazithromycin could improve selectivity because of species-specific interactions with the ribosomal L22 protein. Like other macrolides, these lead compounds display a strong "delayed death phenotype"; however, their early effects on T. gondii replication are more pronounced.

A COST EFFECTIVE PROCESS FOR PREPARING 6,9-IMINO ETHER

The present invention relates to an improved process for the preparation of 6,9-imino ether of formula (I) an intermediate used in preparation of Azithromycin. The present invention further provides a process for preparation of Azithromycin.