87-08-1

Usage

Uses

Used in Pharmaceutical Industry:
Penicillin V is used as an antibacterial agent for the treatment of various infectious diseases. It is effective against a broad spectrum of bacteria, making it a versatile choice for treating different types of infections.
Used in Medical Treatments:
Penicillin V is used for the treatment of bronchitis, pneumonia, angina, scarlet fever, gonorrhea, syphilis, and purulent skin and soft-tissue wounds. Its broad-spectrum activity against both Gram-positive and Gram-negative bacteria makes it a valuable tool in managing a wide range of infections.
Used in Research and Development:
As a contaminant of emerging concern (CECs), Penicillin V is also used in research and development to study its potential environmental impact and to develop methods for its detection and removal from various sources.
Chemical Properties:
Penicillin V is a crystalline solid, which contributes to its stability and ease of handling in pharmaceutical formulations.

Antimicrobial activity

The antibacterial spectrum and level of activity are similar to that of benzylpenicillin. Enteric Gram-negative bacilli are highly resistant.

Air & Water Reactions

Insoluble in water.

Reactivity Profile

Stable in air up to 37%; relatively stable to acid. PENICILLIN V is incompatible with acids, oxidizing agents (especially in the presence of trace metals), heavy metal ions such as copper, lead, zinc and mercury; glycerol, sympathomimetic amines, thiomersal, wood alcohols, cetostearyl alcohol, hard paraffins, macrogols, cocoa butter and many ionic an nonionic surface-active agents. PENICILLIN V is also incompatible with alkalis, compounds leached from vulcanized rubber, hydrochlorides of tetracyclines and organic peroxides. Other incompatibilities include reducing agents, alcohols, other hydroxy compounds, self-emulsifying stearyl alcohol, emulsifying wax, lanolin, crude cholinesterated bases, glycol, sugars, amines, aminacrine hydrochloride, ephedrine, procaine, rubber tubing, thiamine hydrochloride, zinc oxide, oxidized cellulose, iodine, iodides, thiols, chlorocresol and resorcinol. PENICILLIN V may also be incompatible with naphthalene oils and vitamin B.

Health Hazard

SYMPTOMS: Symptoms of exposure to PENICILLIN V include hypersensitization, skin rashes, contact dermatitis, oral lesions, fever, eosinophilia, interstitial nephritis, angioedema, serum sickness, anaphylaxis, "Arthus" phenomenon; irritation of the Gastrointestinal tract; phlebitis; bronchoconstriction with severe asthma, or abdominal pain, nausea, vomiting, extreme weakness and fall in blood pressure, diarrhea, and purpuric skin eruptions.

Fire Hazard

Flash point data for PENICILLIN V are not available; however PENICILLIN V is probably combustible.

Pharmacokinetics

Oral absorption: 40–70% Cmax 250 mg oral: 2 mg/L after 1 h Plasma half-life: c. 0.5 h Volume of distribution: 0.2 L/kg Plasma protein binding: 80% Absorption Owing to acid stability, it is not destroyed in the stomach, but absorption is variable, about 30% remaining in the feces. Absorption is better after administration in the fasting state. Metabolism and excretion It is fairly extensively metabolized and degraded in the bowel. Some 60% of the dose is excreted in the urine, 25% in the unchanged form and the remainder as metabolites.

Clinical Use

In 1948, Behrens et al. reported penicillin V, phenoxymethylpenicillin(Pen Vee, V-Cillin) as a biosyntheticproduct. It was not until 1953, however, that its clinicalvalue was recognized by some European scientists. Sincethen, it has enjoyed wide use because of its resistance tohydrolysis by gastric juice and its ability to produce uniformconcentrations in blood (when administered orally). Thefree acid requires about 1,200 mL of water to dissolve 1 g, and it has an activity of 1,695 units/mg. For parenteralsolutions, the potassium salt is usually used. This salt is verysoluble in water. Solutions of it are made from the dry saltat the time of administration. Oral dosage forms of thepotassium salt are also available, providing rapid, effectiveplasma concentrations of this penicillin. The salt of phenoxymethylpenicillinwith N,N'-bis(dehydroabietyl)ethylenediamine(hydrabamine, Compocillin-V) provides a verylong-acting form of PENICILLIN V. Its high water insolubilitymakes it a desirable compound for aqueous suspensionsused as liquid oral dosage forms.

Clinical Use

It may be prescribed for many indications for which benzylpenicillin is suitable, including streptococcal pharyngitis and skin sepsis, but is not recommended for initial therapy of serious infections. It is useful for continuation therapy after initial control of the disease by parenteral benzylpenicillin when prolonged treatment is required. It has been used prophylactically in recurrent pneumococcal meningitis after head injury and in rheumatic fever. It is not appropriate for infections caused by H. influenzae or Gram-negative bacteria, and is not recommended for the treatment of gonorrhea, syphilis or leptospirosis.

Side effects

Those common to penicillins. As with all penicillins, patients with a history of hypersensitivity to penicillins should be treated cautiously, as serious anaphylactic responses may occur.

Safety Profile

Poison by intraperitoneal, subcutaneous, and intravenous routes. Human systemic effects by ingestion: impaired liver function, dermatitis, fever. Mutation data reported. When heated to decomposition it emits very toxic fumes of SOx and NOx.

Synthesis

Phenoxymethylpenicillin, [2S-(2α,5α,6β)]-3,3-dimethyl-7-oxo- 6-(phenoxyacetamido)-4-thia-1-azabicyclo[3.2.0]-heptan-2-carboxylic acid (32.1.1.2), is also obtained biotechnologically using the fungus P. chrysogenum as the producer and phenoxyacetic acid as the precursor. As with benzylpenicillin, there is a purely synthetic way of making phenoxymethylpenicillin.

InChI:InChI=1/C16H18N2O5S/c1-16(2)12(15(21)22)18-13(20)11(14(18)24-16)17-10(19)8-23-9-6-4-3-5-7-9/h3-7,11-12,14H,8H2,1-2H3,(H,17,19)(H,21,22)/t11-,12+,14-/m1/s1

Synthetic route

6-Aminopenicillanic Acid (551-16-6) + methyl 2-phenoxyacetate (2065-23-8) → penicilin V (87-08-1)

Conditions	Yield
With recombinant Streptomyces lavendulae penicillinacylase In dimethyl sulfoxide at 30℃; for 10.8h; pH=7; Catalytic behavior; Kinetics; Concentration; pH-value; Solvent; Time; Enzymatic reaction;	94.5%

Penicillin-V-2'-bromethylester (65538-78-5) → penicilin V (87-08-1)

Conditions	Yield
With lithium cobalt(I)-phthalocyanine; phenol In acetone for 4h; Ambient temperature;	81%

(R)-2-[(2R,3R)-2-[(2R,3R)-1-((R)-1-Carboxy-2-methyl-propyl)-4-oxo-3-(2-phenoxy-acetylamino)-azetidin-2-yldisulfanyl]-4-oxo-3-(2-phenoxy-acetylamino)-azetidin-1-yl]-3-methyl-butyric acid → penicilin V (87-08-1)

Conditions	Yield
With ethylenediaminetetraacetic acid; dihydrogen peroxide; iron(II) sulfate; ascorbic acid In water	1.3%

(R)-((2R)-4t-carboxy-5,5-dimethyl-thiazolidin-2r-yl)-(2-phenoxy-acetylamino)-acetic acid (123314-55-6) → penicilin V (87-08-1)

Conditions	Yield
With 1,4-dioxane; sodium hydroxide; dicyclohexyl-carbodiimide

6-aminopenicillanic acid trimethylsilyl ester (1025-55-4) + Phenoxyacetyl chloride (701-99-5) → penicilin V (87-08-1)

Conditions	Yield
(i) Et3N, CHCl3, dioxane, (ii) /BRN= 1082694/; Multistep reaction;

6-β-aminopenicillanic acid sodium salt (1203-85-6) + Phenoxyacetyl chloride (701-99-5) → penicilin V (87-08-1)

6β-benzylideneamino-penicillanic acid; 1,1,3,3-tetramethyl-butylamine salt (53059-76-0) + Phenoxyacetyl chloride (701-99-5) → penicilin V (87-08-1)

Conditions	Yield
With sodium 2-ethylhexanoic acid In chloroform-d1

Phenoxyacetyl chloride (701-99-5) + 6R(β)-tritylaminopenicillanic acid (40124-92-3) → penicilin V (87-08-1)

Conditions	Yield
With potassium hydrogencarbonate In acetone

penicillin V sodium salt (1098-87-9) → penicilin V (87-08-1)

Conditions	Yield
Yield given;

Phenoxyacetyl-L-cysteinyl-D-valine → penicilin V (87-08-1)

Conditions	Yield
With ammonium bicarbonate; iron(II) sulfate; catalase; ascorbic acid; diothiothreitol isopenicillin N synthetase from Cephalosporium acremonium CO728;
With isopenicillin N synthetase from Cephalosporium acremonium CO728; oxygen; ammonium bicarbonate; iron(II) sulfate; catalase; ascorbic acid; diothiothreitol In water at 27℃; Michaelis constant, maximum velocity;

(R)-2-[(2R,3R)-2-Mercapto-4-oxo-3-(2-phenoxy-acetylamino)-azetidin-1-yl]-3-methyl-butyric acid → penicilin V (87-08-1)

Conditions	Yield
With ethylenediaminetetraacetic acid; oxygen; iron(II) sulfate; ascorbic acid In water at 37℃; for 2h;

L-valine (72-18-4) + 2-phenoxyacetic acid (122-59-8) → penicilin V (87-08-1)

Conditions	Yield
With phosphate buffer; Penicillium chrysogenum mycelium at 24℃; for 20h; Mechanism; <1-14C>- or <18O2>-labelled;

penicillin V methoxymethyl ester (40966-75-4) → penicilin V (87-08-1)

Conditions	Yield
With water-d2 In d(4)-methanol at 25℃; Rate constant;

cultures of penicillium chrysogenum-stems → penicilin V (87-08-1)

Conditions	Yield
With 2-phenoxyacetic acid

penicillium notatum-stems → penicilin V (87-08-1)

Conditions	Yield
With N-(2-hydroxyethyl)-2-phenoxyacetamide
With bis-[2-(phenoxyacetyl-amino)-ethyl]-disulfide
With 2-phenoxyacetic acid
With 2-Phenoxyethanol

(2S,5R,6R)-3,3-Dimethyl-7-oxo-6-(2-phenoxy-acetylamino)-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid 2-oxo-propyl ester → penicilin V (87-08-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 0.1 M aq. NaOH / acetonitrile View Scheme

(R)-2-[(2R,3R)-2-Mercapto-4-oxo-3-(2-phenoxy-acetylamino)-azetidin-1-yl]-3-methyl-butyric acid 4-methoxy-benzyl ester → penicilin V (87-08-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: CF3COOH / benzene; various solvent(s) / 1 h / 20 °C 2: FeSO4, ascorbic acid, EDTA, O2 / H2O / 2 h / 37 °C View Scheme

3,3-dimethyl-D-cysteine (52-67-5) → penicilin V (87-08-1)

Conditions	Yield
Multi-step reaction with 5 steps 1: sodium acetate; aqueous ethanol 2: dioxane; N2H4+H2O / Behandeln des Reaktionsprodukts mit Essigsaeure und wss. HCl 3: triethylamine; CH2Cl2 4: HCl; CH2Cl2 5: dicyclohexylcarbodiimide; aqueous NaOH; dioxane View Scheme
Multi-step reaction with 6 steps 1: sodium acetate; aqueous ethanol 2: pyridine 3: dioxane; N2H4+H2O / Behandeln des Reaktionsprodukts mit Essigsaeure und wss. HCl 4: triethylamine; CH2Cl2 5: HCl; CH2Cl2 6: dicyclohexylcarbodiimide; aqueous NaOH; dioxane View Scheme

Phenoxyacetyl chloride (701-99-5) → penicilin V (87-08-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: triethylamine; CH2Cl2 2: HCl; CH2Cl2 3: dicyclohexylcarbodiimide; aqueous NaOH; dioxane View Scheme

(4S)-2t-((R)-amino-tert-butoxycarbonyl-methyl)-5,5-dimethyl-thiazolidine-4r-carboxylic acid (1030-50-8) → penicilin V (87-08-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: triethylamine; CH2Cl2 2: HCl; CH2Cl2 3: dicyclohexylcarbodiimide; aqueous NaOH; dioxane View Scheme

(4S)-2t-[(R)-tert-butoxycarbonyl-(2-phenoxy-acetylamino)-methyl]-5,5-dimethyl-thiazolidine-4r-carboxylic acid (1057-37-0, 1105-48-2) → penicilin V (87-08-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: HCl; CH2Cl2 2: dicyclohexylcarbodiimide; aqueous NaOH; dioxane View Scheme

(4S)-2t-((R)-tert-butoxycarbonyl-phthalimido-methyl)-5,5-dimethyl-thiazolidine-4r-carboxylic acid (1056-69-5, 1056-70-8, 6966-35-4, 52049-65-7, 59168-65-9) → penicilin V (87-08-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: dioxane; N2H4+H2O / Behandeln des Reaktionsprodukts mit Essigsaeure und wss. HCl 2: triethylamine; CH2Cl2 3: HCl; CH2Cl2 4: dicyclohexylcarbodiimide; aqueous NaOH; dioxane View Scheme

(4S)-2c-((S)-tert-butoxycarbonyl-phthalimido-methyl)-5,5-dimethyl-thiazolidine-4r-carboxylic acid (59168-65-9) → penicilin V (87-08-1)

Conditions	Yield
Multi-step reaction with 5 steps 1: pyridine 2: dioxane; N2H4+H2O / Behandeln des Reaktionsprodukts mit Essigsaeure und wss. HCl 3: triethylamine; CH2Cl2 4: HCl; CH2Cl2 5: dicyclohexylcarbodiimide; aqueous NaOH; dioxane View Scheme

6-Aminopenicillanic Acid (551-16-6) → penicilin V (87-08-1)

Conditions	Yield
Multi-step reaction with 2 steps 2: KHCO3 / acetone View Scheme
Multi-step reaction with 2 steps 1: CHCl3 2: (i) Et3N, CHCl3, dioxane, (ii) /BRN= 1082694/ View Scheme

6-Aminopenicillanic Acid (551-16-6) + Phenoxyacetyl chloride (701-99-5) → penicilin V (87-08-1)

Conditions	Yield
With potassium hydrogencarbonate In water; acetone at 0 - 20℃; for 1.25h;
Stage #1: 6-Aminopenicillanic Acid; Phenoxyacetyl chloride With sodium hydrogencarbonate In water; acetone at 10 - 15℃; for 0.35h; Stage #2: With sulfuric acid pH=2;

6-Aminopenicillanic Acid (551-16-6) + phenoxyacetyl-d5 chloride (107462-97-5) → penicilin V (87-08-1)

1,1-Diphenylmethanol (91-01-0) + penicilin V (87-08-1) → (2S,5R,6R)-benzhydryl 6-(2-phenoxyacetamido)-3,3-dimethyl-7-oxo-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylate (52141-84-1)

Conditions	Yield
With pyridine; isocyanuric acid In dichloromethane at -7 - -5℃; for 0.666667h;	91.8%

penicilin V (87-08-1) → 6β-phenoxyacetamidopenicillanic acid 1β-sulfoxide (33069-21-5)

Conditions	Yield
With dihydrogen peroxide In dichloromethane at 25 - 30℃; for 6h;	90%

penicilin V (87-08-1) → Caesium; (2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenoxy-acetylamino)-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylate

Conditions	Yield
With cesium hydroxide In tetrahydrofuran pH 5;	88.3%

penicilin V (87-08-1) → penicillin V sodium salt (1098-87-9)

Conditions	Yield
With sodium hydroxide In tetrahydrofuran pH 5;	86%

ethylene dibromide (106-93-4) + penicilin V (87-08-1) → Penicillin-V-2'-bromethylester (65538-78-5)

Conditions	Yield
With sodium carbonate In dimethyl sulfoxide for 20h;	80%

potassium 2-ethylhexanoate + penicilin V (87-08-1) → penicillin V potassium (132-98-9)

Conditions	Yield
In butan-1-ol	80%

penicilin V (87-08-1) → Lithium; (2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenoxy-acetylamino)-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylate

Conditions	Yield
With lithium hydroxide In tetrahydrofuran; water pH 5;	78.3%

1,2-diamino-benzene (95-54-5) + penicilin V (87-08-1) → C22H24N4O4S

Conditions	Yield
In ethanol for 7h; Inert atmosphere; Reflux;	77%

penicilin V (87-08-1) → GENERIC INORGANIC CATION; (2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenoxy-acetylamino)-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylate

Conditions	Yield
With rubidium hydroxide In tetrahydrofuran pH 5;	76.8%

alanine trichloroethylester (63478-48-8) + penicilin V (87-08-1) → (S)-2-{[(2S,5R,6R)-3,3-Dimethyl-7-oxo-6-(2-phenoxy-acetylamino)-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carbonyl]-amino}-propionic acid 2,2,2-trichloro-ethyl ester (113322-06-8)

Conditions	Yield
With diisopropyl-carbodiimide In dichloromethane	69%

H-S-Leu-OTce (69472-81-7) + penicilin V (87-08-1) → (S)-2-{[(2S,5R,6R)-3,3-Dimethyl-7-oxo-6-(2-phenoxy-acetylamino)-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carbonyl]-amino}-4-methyl-pentanoic acid 2,2,2-trichloro-ethyl ester (113322-04-6)

Conditions	Yield
With diisopropyl-carbodiimide In dichloromethane	67%

L-Val-OCH2CCl3 (69472-79-3) + penicilin V (87-08-1) → (S)-2-{[(2S,5R,6R)-3,3-Dimethyl-7-oxo-6-(2-phenoxy-acetylamino)-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carbonyl]-amino}-3-methyl-butyric acid 2,2,2-trichloro-ethyl ester (113322-05-7)

Conditions	Yield
With diisopropyl-carbodiimide In dichloromethane	64%

O-diphenylmethyl 2,2,2-trichloroacetimidate (100865-93-8) + penicilin V (87-08-1) → (2S,5R,6R)-benzhydryl 6-(2-phenoxyacetamido)-3,3-dimethyl-7-oxo-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylate (52141-84-1)

Conditions	Yield
In dichloromethane at 20℃; for 18h; Inert atmosphere;	63%

2,2,2-trichloroethyl glycinate*HBr (40126-72-5) + penicilin V (87-08-1) → {[(2S,5R,6R)-3,3-Dimethyl-7-oxo-6-(2-phenoxy-acetylamino)-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carbonyl]-amino}-acetic acid 2,2,2-trichloro-ethyl ester (113322-07-9)

Conditions	Yield
With triethylamine; diisopropyl-carbodiimide In dichloromethane	50%

H2N-IleOTce (72218-78-1) + penicilin V (87-08-1) → (2S,3S)-2-{[(2S,5R,6R)-3,3-Dimethyl-7-oxo-6-(2-phenoxy-acetylamino)-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carbonyl]-amino}-3-methyl-pentanoic acid 2,2,2-trichloro-ethyl ester (113322-08-0)

Conditions	Yield
With diisopropyl-carbodiimide In dichloromethane	37%

H2N-OTroc-TyrOTce (113351-77-2) + penicilin V (87-08-1) → (S)-2-{[(2S,5R,6R)-3,3-Dimethyl-7-oxo-6-(2-phenoxy-acetylamino)-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carbonyl]-amino}-3-[4-(2,2,2-trichloro-ethoxycarbonyloxy)-phenyl]-propionic acid 2,2,2-trichloro-ethyl ester (113322-11-5)

Conditions	Yield
With diisopropyl-carbodiimide In dichloromethane	36%

(S)-2-Amino-pentanedioic acid bis-(2,2,2-trichloro-ethyl) ester; hydrobromide (113322-03-5) + penicilin V (87-08-1) → (S)-2-{[(2S,5R,6R)-3,3-Dimethyl-7-oxo-6-(2-phenoxy-acetylamino)-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carbonyl]-amino}-pentanedioic acid bis-(2,2,2-trichloro-ethyl) ester (113322-10-4)

Conditions	Yield
With triethylamine; diisopropyl-carbodiimide In dichloromethane	26%

H2N-TrpOTce (113322-02-4) + penicilin V (87-08-1) → (S)-2-{[(2S,5R,6R)-3,3-Dimethyl-7-oxo-6-(2-phenoxy-acetylamino)-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carbonyl]-amino}-3-(1H-indol-3-yl)-propionic acid 2,2,2-trichloro-ethyl ester (113322-09-1)

Conditions	Yield
With diisopropyl-carbodiimide In dichloromethane	14%

penicilin V (87-08-1) → (R)-((2R)-4t-carboxy-5,5-dimethyl-thiazolidin-2r-yl)-(2-phenoxy-acetylamino)-acetic acid (123314-55-6)

Conditions	Yield
With water In 1,4-dioxane at 30℃; Rate constant; Bacillus cereus 569/H β-lactamase I, pH 7; also hydroxy ion instead of enzyme;
With sodium hydroxide

diazomethane (186581-53-3, 908094-01-9) + penicilin V (87-08-1) → (3S,5R,6R)-3-diazoacetyl-2,2-dimethyl-6-phenoxyacetamidopenam (15583-33-2)

Conditions	Yield
(i) Et3N, CH2Cl2, (ii) ClCO2Me, (iii) /BRN= 102415/; Multistep reaction;

diazomethane (186581-53-3, 908094-01-9) + penicilin V (87-08-1) → methyl (2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenoxyacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate (2315-05-1)

Conditions	Yield
In diethyl ether

methanol (67-56-1) + penicilin V (87-08-1) → methyl (2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenoxyacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate (2315-05-1)

Conditions	Yield
With pyridine; dicyclohexyl-carbodiimide In dichloromethane

Upstream product

• 123314-55-6 (R)-((2R)-4t-carboxy-5,5-dimethyl-thiazolidin-2r-yl)-(2-phenoxy-acetylamino)-acetic acid 
• 1025-55-4 6-aminopenicillanic acid trimethylsilyl ester 
• 701-99-5 Phenoxyacetyl chloride 
• 1203-85-6 6-β-aminopenicillanic acid sodium salt 
• 53059-76-0 6β-benzylideneamino-penicillanic acid; 1,1,3,3-tetramethyl-butylamine salt 
• 40124-92-3 6R(β)-tritylaminopenicillanic acid 
• 1098-87-9 penicillin V sodium salt 
• 65538-78-5 Penicillin-V-2'-bromethylester 
• 72-18-4 L-valine 
• 122-59-8 2-phenoxyacetic acid 
• 40966-75-4 penicillin V methoxymethyl ester 
• 52-67-5 3,3-dimethyl-D-cysteine 
• 1030-50-8 (4S)-2t-((R)-amino-tert-butoxycarbonyl-methyl)-5,5-dimethyl-thiazolidine-4r-carboxylic acid 
• 1057-37-0 (4S)-2t-[(R)-tert-butoxycarbonyl-(2-phenoxy-acetylamino)-methyl]-5,5-dimethyl-thiazolidine-4r-carboxylic acid 

Downstream Products

• 123314-55-6 (R)-((2R)-4t-carboxy-5,5-dimethyl-thiazolidin-2r-yl)-(2-phenoxy-acetylamino)-acetic acid 
• 15583-33-2 (3S,5R,6R)-3-diazoacetyl-2,2-dimethyl-6-phenoxyacetamidopenam 
• 2315-05-1 methyl (2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenoxyacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate 
• 19707-30-3 6β-(2-phenoxy-acetylamino)-penicillanic acid ethyl ester 
• 1447-54-7 6β-(2-phenoxy-acetylamino)-penicillanic acid methoxyamide 
• 10234-58-9 6β-(2-phenoxy-acetylamino)-penicillanic acid pyridin-4-ylmethoxy-amide 
• 4052-70-4 6β-(2-phenoxy-acetylamino)-penicillanic acid phenethyloxyamide 
• 10047-62-8 (Ξ)-2-[6β-(2-phenoxy-acetylamino)-penicillanoylaminooxy]-butyric acid ethyl ester 
• 4052-73-7 6β-(2-phenoxy-acetylamino)-penicillanic acid benzyloxyamide 
• 4266-57-3 6β-(2-phenoxy-acetylamino)-penicillanic acid 2-phenyl-propoxyamide 
• 4052-72-6 6β-(2-phenoxy-acetylamino)-penicillanic acid methyl-((Ξ)-2-phenyl-propoxy)-amide 
• 4052-71-5 6β-(2-phenoxy-acetylamino)-penicillanic acid methyl-((Ξ)-1-methyl-2-phenyl-ethoxy)-amide 
• 5776-67-0 6β-(2-phenoxy-acetylamino)-penicillanic acid 3-phenyl-propoxyamide 
• 5776-63-6 2-{[6β-(2-phenoxy-acetylamino)-penicillanoylaminooxy]-methyl}-benzoic acid 

Relevant academic research and scientific papers

Partial Elimination of Valine-oxygen During Penicillin Biosynthesis

G.c.-m.s. analysis of the methyl ester of penicillin V obtained on incubating Penicillium chrysogenum mycelium with L-valine demonstrated the elimination of one of the two carboxy-oxygen atoms.

Biomimetic Synthesis of Penicillin

A working chemical model for the carbon-sulphur bond formation step involved in penicillin biosynthesis is presented; thus, oxidation of a monocyclic β-lactam thiol, or its disulphide form, with dioxygen or hydrogen peroxide, catalysed by iron(II) ion, ascorbic acid, and ethylenediaminetetra-acetic acid, results in direct ring closure to penicillins as well as cephams, in a process similar to the enzymatic synthesis.

Kinetically controlled acylation of 6-APA catalyzed by penicillin acylase from Streptomyces lavendulae: effect of reaction conditions in the enzymatic synthesis of penicillin V

Enzymatic synthesis of penicillin V (penV) by acylation of 6-aminopenicillanic acid (6-APA) was carried out using methyl phenoxyacetate (MPOA) as activated acyl donor and soluble penicillin acylase from Streptomyces lavendulae (SlPVA) as biocatalyst. The effect of different reaction conditions on penV synthesis was investigated, such as enzyme concentration, pH, molar ratio of 6-APA to MPOA, as well as presence of DMSO as water-miscible co-solvent at different concentrations. Time-course profiles of all reactions followed the typical pattern of kinetically controlled synthesis (KCS) of β-lactam antibiotics: penV concentration reached a maximum (highest yield or Ymax) and then decreased gradually. Such maximum was higher at pH 7.0, observing that final penV concentration was abruptly reduced when basic pH values were employed in the reaction. Under the selected conditions (100 mM Tris/HCl buffer pH 7.0, 30 °C, 2.7percent (v/v) DMSO, 20 mM MPOA, 0.3 UI/ml of SlPVA), Ymax was enhanced by increasing the substrate molar ratio (6-APA to MPOA) up to 5, reaching a maximum of 94.5percent and a S/H value of 16.4 (ratio of synthetic activity to hydrolytic activity). As a consequence, the use of an excess of 6-APA as nucleophile has allowed us to obtain some of the highest Ymax and S/H values among those reported in literature for KCS of β-lactam antibiotics. Although many penicillin G acylases (PGAs) have been described in kinetically controlled acylations, SlPVA should be considered as a different enzyme in the biocatalytic tool-box for novel potential synthetic processes, mainly due to its different substrate specificity compared to PGAs.

CEPHALOSPORIN DERIVATIVES AND METHODS OF USE

This invention provides cephalosporin derivatives for killing or inhibiting the spread of microorganisms such as non-replicating Mycobacterium tuberculosis and in the treatment of infectious disease.

LIQUID PHARMACEUTICAL FOR ORAL DELIVERY

A liquid pharmaceutical for oral delivery wherein at the time of use, a solid unit dosage form is added to the liquid wherein the unit dosage form is comprised of a substrate soluble in the liquid and a particulate pharmaceutically active material in a pharmaceutically effective amount. At the time of use, the unit dosage form is added to the liquid, without requiring measurement of the liquid, and the entire liquid is consumed to provide for oral delivery of the pharmaceutically effective amount of material.

Method of using deuterated calcium channel blockers

A method of enhancing the efficiency and increasing the duration of action of drugs (e.g. dihydropyridines and anti-bacterials) and particularly of nifedipine and penicillins wherein one or more hydrogen atoms are deuterated and wherein the deuterated drug has unexpectedly improved properties when used in much lower concentrations than unmodified drug. A method for determining the identity and bioequivalency of a new drug is also disclosed wherein the molecular and isotope structure of a new drug is determined by isotope ratio mass spectrometry and compared with the molecular and isotope structure of a known human drug.

Solvolysis of the methoxymethyl protecting group in penicillin derivatives

The methoxymethyl (MOM) moiety, used as protecting group for the carboxyl function of penicillin derivatives, their sulfoxides and sulfones, could be easily cleaved in aqueous methanol at room temperature. The rate of deprotection by solvolysis is not sensitive to the nature of the substituent in position 6, but depends on the state of oxidation of the thiazolidine sulfur.

Prodrug derivatives of carboxylic acid drugs

Novel ester derivatives of carboxylic acid medicaments of formula (I), wherein R--COO--represents the acyloxy residue of a carboxylic acid drug or medicament, n is an integrer from 1 to 3, and R1 and R2 are the same or different and are selected from a group consisting of an alkyl, an alkenyl, an aryl, an aralkyl, a cycloalkyl and which group may be unsubstituted or substituted, or R1 and R2 together with the N forms a 4-, 5-, 6- or 7-membered heterocyclic ring, which in addition to the nitrogen atom may contain one or two further heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and which heterocyclic group may be substituted. These compounds are highly biolabile prodrug forms of the corresponding carboxylic acid compounds and are highly susceptible to undergoing enzymatic hydrolysis in vivo whereas they are highly stable in aqueous solution. The novel derivatives are less irritating to mucosa than the parent carboxylic acids and may provide an improved bio-availability of the drugs.

Extremely Selective and Mild Cleavage of β-Haloalkyl Groups by Cobalt(I)phthalocyanine Anion in Semisyntheses of β-Lactam Antibiotics

Cleavage of β-haloalkyl groups can be performed extremely selectively by cobalt(I)phthalocyanine anion under very mild conditions, qualifying it best in the chemistry of highly sensitive β-lactam antibiotics.This is demonstrated in penicillin and cephalosporin semisyntheses.

New Oxidatively Removable Carboxy Protecting Groups

2,6-Dimethoxybenzyl esters are readily oxidized by 2,3-dichloro-5,6-dicyano benzoquinone (DDQ) to generate the corresponding carboxylic acids.Phenyl esters substituted with hydroxy, methoxy and dimethylamino groups are also efficiently oxidized by ceric ammonium nitrate (CAN) under pH control conditions.