3577-01-3

Basic information

• Product Name: cefaloglycin
• Synonyms: cefaloglycin;Cephaloglycin;(6R,7R)-7-[(R)-2-Amino-2-phenylacetylamino]-3-(acetoxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid;Cephaloglycin(anhydrous);Kafocin;Kefglycin;Lilly-39435;(6R,7R)-3-(acetoxymethyl)-7-[[(2R)-2-amino-2-phenyl-acetyl]amino]-8-keto-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
• CAS NO: 3577-01-3
• Molecular Formula: C₁₈H₁₉N₃O₆S
• Molecular Weight: 405.46
• EINECS: 222-696-7
• Mol File: 3577-01-3.mol
• Article Data: 4

Chemical Properties

• Melting Point: 236.5°C (rough estimate)
• Boiling Point: 217.4°C (rough estimate)
• Flash Point: 414.5°C
• Appearance: /
• Density: 1.3328 (rough estimate)
• Vapor Pressure: 2.14E-24mmHg at 25°C
• Refractive Index: 1.6390 (estimate)
• Storage Temp.: 2-8°C
• Solubility: Aqueous Acid (Slightly), Methanol (Slightly, Heated)
• PKA: pKa 1.71(H2O t=25±2 I=0.1 ) (Uncertain);7.29(H2O t=25±2 I=0.1 ) (Uncertain)
• Water Solubility: 10.5g/L(25 oC)
• Stability: Hygroscopic, Moisture Sensitive, Temperature Sensitive
• CAS DataBase Reference: cefaloglycin(CAS DataBase Reference)
• NIST Chemistry Reference: cefaloglycin(3577-01-3)
• EPA Substance Registry System: cefaloglycin(3577-01-3)

Safety Data

• Hazard Codes: Xn
• Statements: 42/43
• Safety Statements: 36
• Hazardous Substances Data: 3577-01-3(Hazardous Substances Data)

Usage

Originator

Kefglycin,Shionogi,Japan,1969

Uses

Different sources of media describe the Uses of 3577-01-3 differently. You can refer to the following data:
1. Cefaloglycin is a first-generation cephalosporin antibiotic.
2. Antibacterial.

Definition

ChEBI: A cephalosporin antibiotic containing at the 7beta-position of the cephem skeleton an (R)-amino(phenyl)acetamido group.

Manufacturing Process

dl-Phenylglycine is resolved in a conventional manner by reaction with cinchonine, fractional crystallization of the resulting diastereoisomers, and acidification to release the phenylglycine enantiomorphs. D-phenylglycine, thus prepared, is reacted with carbobenzoxy chloride in a conventional manner to produce N-carbobenzoxy-D-phenylglycine. A 0.60 g portion of N-carbobenzoxy-D-phenylglycine is dissolved in 10 ml of dry tetrahydrofuran. The solution is cooled in an ice-salt bath, and to it is added 0.29 ml of triethylamine with stirring over a period of 10 minutes, followed by 0.29 ml of isobutyl chloroformate, after which stirring is continued for 10 minutes at -5°C. During this time, 0.57 g of 7-aminocephalosporanic acid and 0.29 ml of triethylamine are dissolved in 5 ml of tetrahydrofuran and 5 ml of water, and the solution is centrifuged to remove a dark sludge. The clarified solution is cooled in ice and slowly added to the reaction mixture, and stirring is continued in the ice bath for 0.5 hour, followed by one hour at room temperature. The reaction product mixture is a homogenous solution having a pH of about 6. It is evaporated under vacuum to a semisolid residue. To the residue are added 35 ml of water and a few drops of triethylamine to raise the pH to 8. The aqueous solution obtained thereby is extracted successively with 50 ml and 35 ml portions of ethyl acetate, the pH being adjusted to 2 at each extraction with hydrochloric acid. The extracts are combined, filtered, dried over sodium sulfate, stripped of solvent, and evaporated under vacuum. The product is 7-(N-carbobenzoxy-D-α-aminophenylacetamido)cephalosporanic acid in the form of a yellow-white amorphous solid weighing 1.10 g. Of this material 1.0 g is dissolved in 150 ml of warm 95% ethyl alcohol. To the solution is added 1.0 g of 5% palladium on carbon catalyst, and the mixture is hydrogenated at room temperature and atmospheric pressure by bubbling hydrogen into it for 3 hours with stirring. The hydrogenation product is filtered. The solid phase, comprising the catalyst and the desired product, is suspended in ethyl acetate and water and adjusted to pH 2 with hydrochloric acid. The suspension is filtered to remove the catalyst. The aqueous phase is separated from the filtrate, and is evaporated under vacuum to recover the desired product, 7-(D-α-aminophenylacetamido)cephalosporanicacid.

Therapeutic Function

Antibacterial

InChI:InChI=1/C18H19N3O6S/c1-9(22)27-7-11-8-28-17-13(16(24)21(17)14(11)18(25)26)20-15(23)12(19)10-5-3-2-4-6-10/h2-6,12-13,17H,7-8,19H2,1H3,(H,20,23)(H,25,26)/t12-,13-,17-/m1/s1

Synthetic route

(6R)-3-acetoxymethyl-7t-((R)-2-tert-butoxycarbonylamino-2-phenyl-acetylamino)-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (7765-60-8) → cephaloglycin (3577-01-3)

Conditions	Yield
(i) CF3CO2H, (ii) ion exchange resin - form>; Multistep reaction;

(R)-Phenylglycine methyl ester (24461-61-8) + 7-Aminocephalosporanic acid (957-68-6) → cephaloglycin (3577-01-3)

Conditions	Yield
at 30℃; for 3h; Pseudomonas melanogenum KY 3987 and KY 8540; Yield given;

D-phenylglycine methyl ester hydrochloride (19883-41-1) + 7-Aminocephalosporanic acid (957-68-6) → cephaloglycin (3577-01-3)

Conditions	Yield
With potassium phosphate; Pseudomonas melanogenum KY 8541 at 30℃; pH=6.5;

Boc-D-Phg-OH (33125-05-2) → cephaloglycin (3577-01-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: (i) Et3N, (ii) iBuOCOCl, (iii) /BRN= 5406532/ 2: (i) CF3CO2H, (ii) ion exchange resin - form> View Scheme

N,O-bis-(trimethylsilyl)-acetamide (10416-59-8) + cephaloglycin (3577-01-3) → 7β-[D-2-(Chromone-3-carboxamido)-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid

Conditions	Yield
In dichloromethane; ethyl acetate	55%

cephaloglycin (3577-01-3) → cephalosporanic acid (4704-60-3)

Conditions	Yield
	26%

triethylamine salt of cephaloglycine + 1-oxo-6,7-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-2-carboxylic acid (42835-54-1) + cephaloglycin (3577-01-3) + isobutyl chloroformate (543-27-1) + butan-1-ol (71-36-3) + sodium 2-ethylhexanoic acid → (6R)-3-acetoxymethyl-8-oxo-7t-[(R)-2-(1-oxo-6,7-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-2-carbonylamino)-2-phenyl-acetylamino]-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (73253-21-1, 115404-31-4)

Conditions	Yield
With magnesium sulfate; triethylamine In N-methyl-acetamide; diethyl ether; dichloromethane; water

triethylamine salt of cephaloglycine + 5-methyl-1-oxo-6,7-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-2-carboxylic acid (42835-34-7) + cephaloglycin (3577-01-3) + isobutyl chloroformate (543-27-1) + butan-1-ol (71-36-3) + sodium 2-ethylhexanoic acid → (6R)-3-acetoxymethyl-7t-[(R)-2-((Ξ)-5-methyl-1-oxo-6,7-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-2-carbonylamino)-2-phenyl-acetylamino]-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (73253-22-2)

Conditions	Yield
With magnesium sulfate; triethylamine In N-methyl-acetamide; diethyl ether; water

triethylamine salt of cephaloglycine + cephaloglycin (3577-01-3) + 8-(4-formyl-1-piperazinyl)-6,7-dihydro-1-oxo-1H,5H-benzo[ij]quinolizine-2-carboxylic acid (73004-70-3) + isobutyl chloroformate (543-27-1) + butan-1-ol (71-36-3) + sodium 2-ethylhexanoic acid → (6R)-3-acetoxymethyl-7t-{(R)-2-[8-(4-formyl-piperazin-1-yl)-1-oxo-6,7-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-2-carbonylamino]-2-phenyl-acetylamino}-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (73253-23-3)

Conditions	Yield
With magnesium sulfate; triethylamine In N-methyl-acetamide; diethyl ether; water

diethyl ether (60-29-7) + cephaloglycin (3577-01-3) + sodium 2-ethylhexanoic acid → N-[6-[4-[N-Methyl-5-oxo-L-prolylamino]phenyl]-1,2-dihydro-2-oxo-nicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid

Conditions	Yield
With dimethyl sulfoxide In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; N,N-dimethyl acetamide; ethyl acetate

triethylamine salt of cephaloglycine + 2-methyl-6-oxo-1,2-dihydro-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxylic acid (57771-89-8) + cephaloglycin (3577-01-3) + isobutyl chloroformate (543-27-1) + sodium 2-ethylhexanoic acid → 7-[2-(2-methyl-1,2-dihydro-6-oxo-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamido)-2-phenylacetamido]-3-(acetyloxymethyl)-8-oxo-5-thia-1-azabicyclo[4,2,0]oct-2-ene-2-carboxylic acid

Conditions	Yield
With magnesium sulfate; triethylamine In N-methyl-acetamide; diethyl ether; water; butan-1-ol

6-oxo-1,2-dihydro-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxylic acid (40400-68-8) + cephaloglycin (3577-01-3) + isobutyl chloroformate (543-27-1) + sodium 2-ethylhexanoic acid → (6R)-3-acetoxymethyl-8-oxo-7t-[(R)-2-(6-oxo-1,2-dihydro-6H-pyrrolo[3,2,1-ij]quinoline-5-carbonylamino)-2-phenyl-acetylamino]-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (73253-27-7, 115404-30-3)

Conditions	Yield
With triethylamine In N-methyl-acetamide; diethyl ether; water; butan-1-ol

cephaloglycin (3577-01-3) + sodium 2-ethylhexanoic acid → N-[6-[4-(N-acetyl-alpha-aminoisobutyrylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid

Conditions	Yield
In N,N-dimethyl acetamide; water; ethyl acetate

cephaloglycin (3577-01-3) + sodium 2-ethylhexanoic acid → N-[2-[4-(N-Acetyl-D-alanylamino)phenyl]-4-hydroxy-5-pyrimidinyl-carbonyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid

Conditions	Yield
With triethylamine In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; 2-[4-(N-acetyl-D-alanylamino)phenyl]-4-hydroxy-5-pyrimidine carboxylic acid imidazolide; N,N-dimethyl acetamide; water; ethyl acetate

2-[4-(N-acetyl-DL-alanylamino)phenyl]-4-hydroxy-5-pyrimidine carboxylic acid imidazolide (76741-36-1) + N-[2-[4-(N-acetylglycylamino)phenyl]-4-hydroxy-5-pyrimidinylcarbonyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid + cephaloglycin (3577-01-3) + sodium 2-ethylhexanoic acid → N-[2-[4-(N-acetyl-DL-alanylamino)phenyl]-4-hydroxy-5-pyrimidinylcarbonyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid

Conditions	Yield
In N,N-dimethyl acetamide

2-[4-(N-t-butoxycarbonyl-D-alanylamino)phenyl]-4-hydroxy-5-pyrimidine carboxylic acid imidazolide (76718-64-4) + cephaloglycin (3577-01-3) + sodium 2-ethylhexanoic acid → N-[2-[4-(N-t-butoxycarbonyl-D-alanylamino)phenyl]-4-hydroxy-5-pyrimidinylcarbonyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid

Conditions	Yield
In N,N-dimethyl acetamide; water; ethyl acetate

2-[4-(N-acetylglcylamino)phenyl]-4-hydroxy-5-pyrimidine carboxylic acid imidazolide + cephaloglycin (3577-01-3) + sodium 2-ethylhexanoic acid → N-[2-[4-(N-acetylglycylamino)phenyl]-4-hydroxy-5-pyrimidinylcarbonyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid

Conditions	Yield
With sodium hydroxide In N,N-dimethyl acetamide; water; ethyl acetate

cephaloglycin (3577-01-3) → N-[6-[4-(D-alanylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid

Conditions	Yield
With hydrogenchloride; ammonium hydroxide In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; N,N-dimethyl acetamide; dimethyl sulfoxide

isopropyl methyl ether (598-53-8) + cephaloglycin (3577-01-3) → N-[6-[4-(N-Acetyl-4-hydroxy-L-prolylamino)phenyl]-1,2-dihydro-2-oxonicotinyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid

Conditions	Yield
With sodium hydroxide; dimethyl sulfoxide In N,N-dimethyl acetamide; water; ethyl acetate; triethylamine

2-[4-(N-acetyl-DL-prolylamino)phenyl]-4-hydroxy-5-pyrimidine carboxylic acid imidazolide (76718-59-7) + cephaloglycin (3577-01-3) → N-[2-[4-(N-Acetyl-DL-prolylamino)phenyl]-4-hydroxy-5-pyrimidinylcarbonyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxy-methyl-3-cephem-4-carboxylic acid

Conditions	Yield
With hydrogenchloride; triethylamine In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; N,N-dimethyl acetamide; water

2-[4-(N-acetyl-DL-glutaminylamino)phenyl]-4-hydroxy-5-pyrimidine carboxylic acid imidazolide (76718-60-0) + cephaloglycin (3577-01-3) → N-[2-[4-(N-Acetyl-DL-glutaminylamino)phenyl]-4-hydroxy-5-pyrimidinylcarbonyl]-7-[D-2-amino-2phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid

Conditions	Yield
With triethylamine In N,N-dimethyl acetamide

2-[4-(N-acetyl-DL-methionylamino)phenyl]-4-hydroxy-5-pyrimidine]carboxylic acid imidazolide + cephaloglycin (3577-01-3) → N-[2-[4-(N-acetyl-DL-methionylamino)phenyl]-4-hydroxy-5-pyrimidinylcarbonyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid

Conditions	Yield
With triethylamine In N,N-dimethyl acetamide

2-[4-(N-acetyl-alpha-aminoisobutyrylamino)phenyl]-4-hydroxy-5-pyrimidine carboxylic acid imidazolide + cephaloglycin (3577-01-3) → N-[2-[4-(N-acetyl-alpha-aminoisobutyrylamino)phenyl]-4-hydroxy-5-pyrimidinylcarbonyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid

Conditions	Yield
With triethylamine In N,N-dimethyl acetamide

2-[4-(N-acetyl-DL-leucylamino)phenyl]-4-hydroxy-5-pyrimidine carboxylic acid imidazolide (76718-53-1) + cephaloglycin (3577-01-3) → N-[2-[4-(N-Acetyl-DL-leucylamino)phenyl]-4-hydroxy-5-pyrimidinylcarbonyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid

Conditions	Yield
With triethylamine In N,N-dimethyl acetamide

2-[4-(N-acetyl-L-alanylamino)phenyl]-4-hydroxy-5-pyrimidine carboxylic acid imidazolide (76718-57-5) + cephaloglycin (3577-01-3) → N-[2-[4-(N-Acetyl-L-alanylamino)phenyl]-4-hydroxy-5-pyrimidinylcarbonyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxy-methyl-3-cephem-4-carboxylic acid

Conditions	Yield
With sodium hydroxide In N,N-dimethyl acetamide; water; ethyl acetate; sodium 2-ethylhexanoic acid

2-[4-(N-acetyl-L-hydroxyprolylamino)phenyl]-4-hydroxy-5-pyrimidine carboxylic acid N-hydroxysuccinimide ester + cephaloglycin (3577-01-3) → N-[2-[4-(N-acetyl-L-hydroxyprolylamino)phenyl]-4-hydroxy-5-pyrimidinylcarbonyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid

Conditions	Yield
With sodium hydroxide; triethylamine In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; N,N-dimethyl acetamide; water; ethyl acetate

2-[4-(N-acetyl-γ-aminobutyrylamino)phenyl]-4-hydroxy-5-pyrimidine carboxylic acid imidazolide + cephaloglycin (3577-01-3) → N-[2-[4-(N-Acetyl-γ-aminobutyrylamino)phenyl]-4-hydroxy-5-pyrimidinylcarbonyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxy-methyl-3-cephem-4-carboxylic acid

Conditions	Yield
With triethylamine In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; N,N-dimethyl acetamide; ethyl acetate

2-[4-(N-acetyl-D-valylamino)phenyl]-4-hydroxy-5-pyrimidine carboxylic acid imidazolide (76718-63-3) + cephaloglycin (3577-01-3) → N-[2-[4-(N-acetyl-D-valylamino)phenyl]-4-hydroxy-5-pyrimidinylcarbonyl]-7-[D-2-amino-2-phenylacetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid

Conditions	Yield
With sodium hydroxide; triethylamine In N,N-dimethyl acetamide; water; ethyl acetate

Upstream product

• 24461-61-8 (R)-Phenylglycine methyl ester 
• 957-68-6 7-Aminocephalosporanic acid 
• 19883-41-1 D-phenylglycine methyl ester hydrochloride 
• 33125-05-2 Boc-D-Phg-OH 
• 7765-60-8 (6R)-3-acetoxymethyl-7t-((R)-2-tert-butoxycarbonylamino-2-phenyl-acetylamino)-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid 

Downstream Products

• 73253-21-1 (6R)-3-acetoxymethyl-8-oxo-7t-[(R)-2-(1-oxo-6,7-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-2-carbonylamino)-2-phenyl-acetylamino]-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid 
• 73253-22-2 (6R)-3-acetoxymethyl-7t-[(R)-2-((Ξ)-5-methyl-1-oxo-6,7-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-2-carbonylamino)-2-phenyl-acetylamino]-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid 
• 73253-23-3 (6R)-3-acetoxymethyl-7t-{(R)-2-[8-(4-formyl-piperazin-1-yl)-1-oxo-6,7-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-2-carbonylamino]-2-phenyl-acetylamino}-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid 
• 73253-27-7 (6R)-3-acetoxymethyl-8-oxo-7t-[(R)-2-(6-oxo-1,2-dihydro-6H-pyrrolo[3,2,1-ij]quinoline-5-carbonylamino)-2-phenyl-acetylamino]-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid 

Relevant articles and documents

Beta lactam production

A new process is described for the production of 7-alpha-aminoacyl-cephalosporin free from halogen-containing solvents by acylating 7-amino-ceph-3-em-4-carboxylic acid or a derivative thereof in a halogen-free solvent.

Enzymatic production of amoxicillin by β-lactamase-deficient mutants of Pseudomonas melanogenum KY 3987

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