59995-64-1

Basic information

• Product Name: Thienamycin
• Synonyms: [SR-[5α，6α(R^^)]]-3-[(2-Aminoethyl)thio]-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid;(5R)-3-(2-Aminoethylthio)-6β-[(R)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hepta-2-ene-2-carboxylic acid;(5R)-3-[(2-Aminoethyl)thio]-6β-[(R)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid;(5R,6R)-3-(2-aminoethylsulfanyl)-6-[(1R)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid;(5R,6R)-3-(2-aminoethylthio)-6-[(1R)-1-hydroxyethyl]-7-keto-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid;(5R,6R)-3-(2-azanylethylsulfanyl)-6-[(1R)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid;IMipeneM IMpurity A
• CAS NO: 59995-64-1
• Molecular Formula: C₁₁H₁₆N₂O₄S
• Molecular Weight: 272.323
• EINECS: 203-170-6
• Mol File: 59995-64-1.mol

Chemical Properties

• Boiling Point: 514°C at 760 mmHg
• Flash Point: 264.7°C
• Appearance: /
• Density: 1.5g/cm³
• Vapor Pressure: 1.02E-12mmHg at 25°C
• Refractive Index: 1.662
• Storage Temp.: Hygroscopic, -86°C Freezer, Under inert atmosphere
• Solubility: Chloroform (Slightly), Methanol (Slightly), Water (Slightly)
• PKA: 4.20±0.40(Predicted)
• Stability: Hygroscopic, Temperature Sensitive, Very Unstable
• CAS DataBase Reference: Thienamycin(CAS DataBase Reference)
• NIST Chemistry Reference: Thienamycin(59995-64-1)
• EPA Substance Registry System: Thienamycin(59995-64-1)

Safety Data

• Hazardous Substances Data: 59995-64-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Thienamycin is used as an antibiotic for treating various bacterial infections. Its broad-spectrum activity against both Gram-positive and Gram-negative bacteria, coupled with its resistance to β-lactamase enzymes, makes it an effective choice for combating a variety of infections, including those caused by antibiotic-resistant strains.
Used in Research and Development:
In the field of medical research, Thienamycin serves as a valuable compound for studying the mechanisms of antibiotic action and resistance. Its unique properties can be harnessed to develop new drugs or improve existing ones, potentially leading to more effective treatments for bacterial infections.
Used in Hospital Settings:
Thienamycin is utilized in hospitals and healthcare facilities as a potent antibiotic for the treatment of severe or life-threatening bacterial infections. Its effectiveness against a wide range of bacteria and resistance to bacterial enzymes make it a crucial tool in the management of complex and challenging infections.

InChI:InChI=1/C11H16N2O4S/c1-5(14)8-6-4-7(18-3-2-12)9(11(16)17)13(6)10(8)15/h5-6,8,14H,2-4,12H2,1H3,(H,16,17)/t5-,6-,8-/m1/s1

Synthetic route

p-nitrobenzyl (5R,6S)-2-<<2-<<<(p-nitrobenzyl)oxy>carbonyl>amino>ethyl>thio>-6-<(R)-1-hydroxyethyl>carbapen-2-em-3-carboxylate (64067-13-6) → thienamycin (59995-64-1)

Conditions	Yield
With hydrogen; palladium on activated charcoal under 2068.6 Torr;

formamidine acetic acid (3473-63-0) + imipenem (118334-32-0, 118395-94-1) → thienamycin (59995-64-1) + (R)-5-((1R,2R)-1-Carbamoyl-2-hydroxy-propyl)-3-(2-formimidoylamino-ethylsulfanyl)-1-formyl-4,5-dihydro-1H-pyrrole-2-carboxylic acid (130641-22-4)

Conditions	Yield
at 20℃; Rate constant; Product distribution;

imipenem (118334-32-0, 118395-94-1) → thienamycin (59995-64-1)

Conditions	Yield
With hydroxide at 20℃; Rate constant;

(3S,4R)-3-[(R)-1-hydroxyethyl]-4-[3-benzyloxycarbonyl-2-oxo-3-diazopropyl] azetidin-2-one → thienamycin (59995-64-1)

Conditions	Yield
Multistep reaction;

2-Diazo-4-[(2R,3S)-3-((R)-1-formyloxy-ethyl)-4-oxo-azetidin-2-yl]-3-oxo-butyric acid 4-nitro-phenyl ester + ethane-1,2-dithiol (540-63-6) → thienamycin (59995-64-1)

Conditions	Yield
With toluene-4-sulfonic acid In dichloromethane; isopropyl alcohol at 25℃; for 96h;

4-nitrobenzyl (2R,5R,6S)-6-[(1R)-1-hydroxyethyl]-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate (75363-99-4) → thienamycin (59995-64-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: DMAP, i-Pr2NEt / acetonitrile / 0 °C 2: 70 percent / i-Pr2NEt / acetonitrile / -5 °C 3: H2 / Pd/C / 2068.6 Torr View Scheme

(3S,4R)-3-[(R)-1-hydroxyethyl]-4-[3-(4-nitrobenzyl)-oxycarbonyl-2-oxopropyl]azetidin-2-one (75321-07-2) → thienamycin (59995-64-1)

Conditions	Yield
Multi-step reaction with 5 steps 1: 90 percent / p-carboxybenzenesulfonyl azide, Et3N / acetonitrile / 0 - 20 °C 2: rhodium(II) acetate / benzene / 80 °C 3: DMAP, i-Pr2NEt / acetonitrile / 0 °C 4: 70 percent / i-Pr2NEt / acetonitrile / -5 °C 5: H2 / Pd/C / 2068.6 Torr View Scheme

(3S,4R)-3-[(R)-1-hydroxyethyl)-4-[3-(4-nitrobenzyl)oxycarbonyl-2-oxo-3-diazopropyl]azetidin-2-one (74288-39-4) → thienamycin (59995-64-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: rhodium(II) acetate / benzene / 80 °C 2: DMAP, i-Pr2NEt / acetonitrile / 0 °C 3: 70 percent / i-Pr2NEt / acetonitrile / -5 °C 4: H2 / Pd/C / 2068.6 Torr View Scheme

(3S,4R)-1-(tert-Butyldimethylsilyl)-3-<(1R)-1-hydroxyethyl>-4-(carboxymethyl)azetidin-2-one (75321-05-0) → thienamycin (59995-64-1)

Conditions	Yield
Multi-step reaction with 8 steps 1: tetrahydrofuran / Ambient temperature 2: 86 percent / tetrahydrofuran / Ambient temperature 3: HCl / methanol 4: 90 percent / p-carboxybenzenesulfonyl azide, Et3N / acetonitrile / 0 - 20 °C 5: rhodium(II) acetate / benzene / 80 °C 6: DMAP, i-Pr2NEt / acetonitrile / 0 °C 7: 70 percent / i-Pr2NEt / acetonitrile / -5 °C 8: H2 / Pd/C / 2068.6 Torr View Scheme

(S)-1-(tert-Butyl-dimethyl-silanyl)-4-(2-trimethylsilanyl-[1,3]dithian-2-ylmethyl)-azetidin-2-one (75321-01-6) → thienamycin (59995-64-1)

Conditions	Yield
Multi-step reaction with 12 steps 1: 82 percent Turnov. / LDA / tetrahydrofuran / -78 °C 2: K-Selectride, KI / diethyl ether / 25 °C 3: 93 percent / HgCl2, HgO / methanol; H2O / Heating 4: 76 percent / hydrogen peroxide / methanol; H2O 5: tetrahydrofuran / Ambient temperature 6: 86 percent / tetrahydrofuran / Ambient temperature 7: HCl / methanol 8: 90 percent / p-carboxybenzenesulfonyl azide, Et3N / acetonitrile / 0 - 20 °C 9: rhodium(II) acetate / benzene / 80 °C 10: DMAP, i-Pr2NEt / acetonitrile / 0 °C 11: 70 percent / i-Pr2NEt / acetonitrile / -5 °C 12: H2 / Pd/C / 2068.6 Torr View Scheme
Multi-step reaction with 11 steps 1: LDA / tetrahydrofuran / -78 °C 2: 93 percent / HgCl2, HgO / methanol; H2O / Heating 3: 76 percent / hydrogen peroxide / methanol; H2O 4: tetrahydrofuran / Ambient temperature 5: 86 percent / tetrahydrofuran / Ambient temperature 6: HCl / methanol 7: 90 percent / p-carboxybenzenesulfonyl azide, Et3N / acetonitrile / 0 - 20 °C 8: rhodium(II) acetate / benzene / 80 °C 9: DMAP, i-Pr2NEt / acetonitrile / 0 °C 10: 70 percent / i-Pr2NEt / acetonitrile / -5 °C 11: H2 / Pd/C / 2068.6 Torr View Scheme

(3S,4R)-1-(t-butyldimethylsilyl)-3-[(R)-1-hydroxyethyl]-4-(2-oxo-2-trimethylsilylethyl)-azetidin-2-one (75321-04-9) → thienamycin (59995-64-1)

Conditions

Yield

Multi-step reaction with 9 steps 1: 76 percent / hydrogen peroxide / methanol; H2O 2: tetrahydrofuran / Ambient temperature 3: 86 percent / tetrahydrofuran / Ambient temperature 4: HCl / methanol 5: 90 percent / p-carboxybenzenesulfonyl azide, Et3N / acetonitrile / 0 - 20 °C 6: rhodium(II) acetate / benzene / 80 °C 7: DMAP, i-Pr2NEt / acetonitrile / 0 °C 8: 70 percent / i-Pr2NEt / acetonitrile / -5 °C 9: H2 / Pd/C / 2068.6 Torr View Scheme

(3S,4R)-1-(tert-Butyl-dimethyl-silanyl)-3-((R)-1-hydroxy-ethyl)-4-(2-imidazol-1-yl-2-oxo-ethyl)-azetidin-2-one (75333-88-9) → thienamycin (59995-64-1)

Conditions	Yield
Multi-step reaction with 7 steps 1: 86 percent / tetrahydrofuran / Ambient temperature 2: HCl / methanol 3: 90 percent / p-carboxybenzenesulfonyl azide, Et3N / acetonitrile / 0 - 20 °C 4: rhodium(II) acetate / benzene / 80 °C 5: DMAP, i-Pr2NEt / acetonitrile / 0 °C 6: 70 percent / i-Pr2NEt / acetonitrile / -5 °C 7: H2 / Pd/C / 2068.6 Torr View Scheme

(3S,4R)-3-Acetyl-1-(tert-butyl-dimethyl-silanyl)-4-(2-trimethylsilanyl-[1,3]dithian-2-ylmethyl)-azetidin-2-one (77551-48-5) → thienamycin (59995-64-1)

Conditions

Yield

Multi-step reaction with 11 steps 1: K-Selectride, KI / diethyl ether / 25 °C 2: 93 percent / HgCl2, HgO / methanol; H2O / Heating 3: 76 percent / hydrogen peroxide / methanol; H2O 4: tetrahydrofuran / Ambient temperature 5: 86 percent / tetrahydrofuran / Ambient temperature 6: HCl / methanol 7: 90 percent / p-carboxybenzenesulfonyl azide, Et3N / acetonitrile / 0 - 20 °C 8: rhodium(II) acetate / benzene / 80 °C 9: DMAP, i-Pr2NEt / acetonitrile / 0 °C 10: 70 percent / i-Pr2NEt / acetonitrile / -5 °C 11: H2 / Pd/C / 2068.6 Torr View Scheme

(3S,4R)-1-(t-butyldimethylsilyl)-3-[(R)-1-hydroxyethyl]-4-(3-p-nitrobenzyloxycarbonyl-2-oxopropyl)-azetidin-2-one (75321-06-1) → thienamycin (59995-64-1)

Conditions	Yield
Multi-step reaction with 6 steps 1: HCl / methanol 2: 90 percent / p-carboxybenzenesulfonyl azide, Et3N / acetonitrile / 0 - 20 °C 3: rhodium(II) acetate / benzene / 80 °C 4: DMAP, i-Pr2NEt / acetonitrile / 0 °C 5: 70 percent / i-Pr2NEt / acetonitrile / -5 °C 6: H2 / Pd/C / 2068.6 Torr View Scheme

p-nitrobenzyl (5R,6S)-2-diphenoxy phosphoryloxy-6-[(R)-1-hydroxyethyl]-1-carbapen-2-em-3-carboxylate (75321-08-3) → thienamycin (59995-64-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 70 percent / i-Pr2NEt / acetonitrile / -5 °C 2: H2 / Pd/C / 2068.6 Torr View Scheme

(3S,4R)-1-(tert-Butyl-dimethyl-silanyl)-3-(1-hydroxy-ethyl)-4-(2-trimethylsilanyl-[1,3]dithian-2-ylmethyl)-azetidin-2-one (75321-02-7, 75363-98-3, 75364-00-0, 80735-71-3) → thienamycin (59995-64-1)

Conditions

Yield

Multi-step reaction with 12 steps 1: 88 percent / TFAA, Me2SO, Et3N / CH2Cl2 / -78 °C 2: K-Selectride, KI / diethyl ether / 25 °C 3: 93 percent / HgCl2, HgO / methanol; H2O / Heating 4: 76 percent / hydrogen peroxide / methanol; H2O 5: tetrahydrofuran / Ambient temperature 6: 86 percent / tetrahydrofuran / Ambient temperature 7: HCl / methanol 8: 90 percent / p-carboxybenzenesulfonyl azide, Et3N / acetonitrile / 0 - 20 °C 9: rhodium(II) acetate / benzene / 80 °C 10: DMAP, i-Pr2NEt / acetonitrile / 0 °C 11: 70 percent / i-Pr2NEt / acetonitrile / -5 °C 12: H2 / Pd/C / 2068.6 Torr View Scheme

(3S,4R)-1-(tert-Butyl-dimethyl-silanyl)-3-((R)-1-hydroxy-ethyl)-4-(2-trimethylsilanyl-[1,3]dithian-2-ylmethyl)-azetidin-2-one (75321-02-7) → thienamycin (59995-64-1)

Conditions

Yield

Multi-step reaction with 10 steps 1: 93 percent / HgCl2, HgO / methanol; H2O / Heating 2: 76 percent / hydrogen peroxide / methanol; H2O 3: tetrahydrofuran / Ambient temperature 4: 86 percent / tetrahydrofuran / Ambient temperature 5: HCl / methanol 6: 90 percent / p-carboxybenzenesulfonyl azide, Et3N / acetonitrile / 0 - 20 °C 7: rhodium(II) acetate / benzene / 80 °C 8: DMAP, i-Pr2NEt / acetonitrile / 0 °C 9: 70 percent / i-Pr2NEt / acetonitrile / -5 °C 10: H2 / Pd/C / 2068.6 Torr View Scheme

2-Diazo-4-[(2R,3S)-3-((S)-1-hydroxy-ethyl)-4-oxo-azetidin-2-yl]-3-oxo-butyric acid 4-nitro-phenyl ester → thienamycin (59995-64-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 95 percent / Ph3P, HCOOH, EtO2CNNCO2Et / Mitsunobu's method 2: p-toluenesulfonic acid / CH2Cl2; propan-2-ol / 96 h / 25 °C View Scheme

4-{(2R,3S)-3-[(S)-1-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-4-oxo-azetidin-2-yl}-2-diazo-3-oxo-butyric acid 4-nitro-phenyl ester → thienamycin (59995-64-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: HCl / methanol; H2O 2: 95 percent / Ph3P, HCOOH, EtO2CNNCO2Et / Mitsunobu's method 3: p-toluenesulfonic acid / CH2Cl2; propan-2-ol / 96 h / 25 °C View Scheme

(3R,4R)-4-acetoxy-3-<(S)-1-(tert-butyldimethylsilyloxy)ethyl>-2-azetidinone (78963-60-7) → thienamycin (59995-64-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: 83 percent / ZnCl2 / CH2Cl2 2: HCl / methanol; H2O 3: 95 percent / Ph3P, HCOOH, EtO2CNNCO2Et / Mitsunobu's method 4: p-toluenesulfonic acid / CH2Cl2; propan-2-ol / 96 h / 25 °C View Scheme

(2S,3S)-1-(tert-Butyl-dimethyl-silanyl)-3-[(S)-1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-4-oxo-azetidine-2-carbaldehyde (102046-01-5) → thienamycin (59995-64-1)

Conditions	Yield
Multi-step reaction with 6 steps 1: 86 percent / Jones reagent 2: 81 percent / acetic acid 3: 83 percent / ZnCl2 / CH2Cl2 4: HCl / methanol; H2O 5: 95 percent / Ph3P, HCOOH, EtO2CNNCO2Et / Mitsunobu's method 6: p-toluenesulfonic acid / CH2Cl2; propan-2-ol / 96 h / 25 °C View Scheme

(2R,3S)-1-(tert-Butyl-dimethyl-silanyl)-3-[(S)-1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-4-oxo-azetidine-2-carbaldehyde (102129-89-5) → thienamycin (59995-64-1)

Conditions	Yield
Multi-step reaction with 6 steps 1: 96 percent / Jones reagent 2: 80 percent / acetic acid 3: 83 percent / ZnCl2 / CH2Cl2 4: HCl / methanol; H2O 5: 95 percent / Ph3P, HCOOH, EtO2CNNCO2Et / Mitsunobu's method 6: p-toluenesulfonic acid / CH2Cl2; propan-2-ol / 96 h / 25 °C View Scheme

(2S,3S)-1-(tert-Butyl-dimethyl-silanyl)-3-[(S)-1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-4-oxo-azetidine-2-carboxylic acid (102129-88-4) → thienamycin (59995-64-1)

Conditions	Yield
Multi-step reaction with 5 steps 1: 81 percent / acetic acid 2: 83 percent / ZnCl2 / CH2Cl2 3: HCl / methanol; H2O 4: 95 percent / Ph3P, HCOOH, EtO2CNNCO2Et / Mitsunobu's method 5: p-toluenesulfonic acid / CH2Cl2; propan-2-ol / 96 h / 25 °C View Scheme

(2R,3S)-1-(tert-Butyl-dimethyl-silanyl)-3-[(S)-1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-4-oxo-azetidine-2-carboxylic acid (102129-90-8) → thienamycin (59995-64-1)

Conditions	Yield
Multi-step reaction with 5 steps 1: 80 percent / acetic acid 2: 83 percent / ZnCl2 / CH2Cl2 3: HCl / methanol; H2O 4: 95 percent / Ph3P, HCOOH, EtO2CNNCO2Et / Mitsunobu's method 5: p-toluenesulfonic acid / CH2Cl2; propan-2-ol / 96 h / 25 °C View Scheme

<3S,4S(E)>-3-<1(S)-hydroxyethyl>-1-(4-methoxyphenyl)-4-(2-phenylethenyl)-2-azetidinone (101977-77-9) → thienamycin (59995-64-1)

Conditions

Yield

Multi-step reaction with 9 steps 1: 88 percent / silylation 2: 1.) cerric ammonium nitrate / 2.) silylation 3: 91 percent / 1.) O3; 2.) Me2S / CH2Cl2 / -78 °C 4: 96 percent / Jones reagent 5: 80 percent / acetic acid 6: 83 percent / ZnCl2 / CH2Cl2 7: HCl / methanol; H2O 8: 95 percent / Ph3P, HCOOH, EtO2CNNCO2Et / Mitsunobu's method 9: p-toluenesulfonic acid / CH2Cl2; propan-2-ol / 96 h / 25 °C View Scheme

(1'S,3S,4S)-3-(1'-<(tert-butyldimethylsilyl)oxy>ethyl)-1-(4'-methoxyphenyl)-4-(2'-phenylethenyl)-2-azetidinone (101977-83-7) → thienamycin (59995-64-1)

Conditions	Yield
Multi-step reaction with 8 steps 1: 1.) cerric ammonium nitrate / 2.) silylation 2: 91 percent / 1.) O3; 2.) Me2S / CH2Cl2 / -78 °C 3: 96 percent / Jones reagent 4: 80 percent / acetic acid 5: 83 percent / ZnCl2 / CH2Cl2 6: HCl / methanol; H2O 7: 95 percent / Ph3P, HCOOH, EtO2CNNCO2Et / Mitsunobu's method 8: p-toluenesulfonic acid / CH2Cl2; propan-2-ol / 96 h / 25 °C View Scheme

(3S,4R)-1-(tert-Butyl-dimethyl-silanyl)-3-[(S)-1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-4-((E)-styryl)-azetidin-2-one (102045-99-8) → thienamycin (59995-64-1)

Conditions	Yield
Multi-step reaction with 7 steps 1: 85 percent / 1.) O3; 2.) Me2S / CH2Cl2 / -78 °C 2: 86 percent / Jones reagent 3: 81 percent / acetic acid 4: 83 percent / ZnCl2 / CH2Cl2 5: HCl / methanol; H2O 6: 95 percent / Ph3P, HCOOH, EtO2CNNCO2Et / Mitsunobu's method 7: p-toluenesulfonic acid / CH2Cl2; propan-2-ol / 96 h / 25 °C View Scheme

(3S,4S)-1-(tert-Butyl-dimethyl-silanyl)-3-[(S)-1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-4-((E)-styryl)-azetidin-2-one (102046-00-4) → thienamycin (59995-64-1)

Conditions	Yield
Multi-step reaction with 7 steps 1: 91 percent / 1.) O3; 2.) Me2S / CH2Cl2 / -78 °C 2: 96 percent / Jones reagent 3: 80 percent / acetic acid 4: 83 percent / ZnCl2 / CH2Cl2 5: HCl / methanol; H2O 6: 95 percent / Ph3P, HCOOH, EtO2CNNCO2Et / Mitsunobu's method 7: p-toluenesulfonic acid / CH2Cl2; propan-2-ol / 96 h / 25 °C View Scheme

(3R,4R)-4-acetoxy-3-[(1R)-1-hydroxyethyl]azetidin-2-one (87037-95-4, 103365-27-1, 119720-15-9, 122673-16-9, 122673-17-0, 82938-53-2) → thienamycin (59995-64-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 81 percent / ZnI2 View Scheme

(2S,3S)-3-Acetyl-1-(tert-butyl-dimethyl-silanyl)-4-oxo-azetidine-2-carboxylic acid (82938-52-1) → thienamycin (59995-64-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: 70 percent / Diisopropylamine*borane, magnesium trifluoroacetate 2: 82 percent / dimethylformamide; acetic acid / 70 °C 3: 81 percent / ZnI2 View Scheme

thienamycin (59995-64-1) + 4-nitrobenzyl chloroformate (4457-32-3) → N-<<(p-nitrobenzyl)oxy>carbonyl>thienamycin lithium salt (64066-86-0)

Conditions	Yield
With lithium hydroxide; sodium hydrogencarbonate 1.) H2O, dioxane, ice/NaCl bath; 2.) ethyl acetate, 0.05 M LiOH; Yield given. Multistep reaction;
With lithium hydroxide; sodium hydrogencarbonate 1.) H2O, dioxane, 10 min, 2.) EtOAc; Yield given. Multistep reaction;

thienamycin (59995-64-1) → p-nitrobenzyl (5R,6S)-2-<<2-<<<(p-nitrobenzyl)oxy>carbonyl>amino>ethyl>thio>-6-<(R)-1-hydroxyethyl>carbapen-2-em-3-carboxylate (64067-13-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) NaHCO3, 2.) LiOH / 1.) H2O, dioxane, 10 min, 2.) EtOAc 2: HMPA / 2.5 h / Ambient temperature View Scheme
Multi-step reaction with 2 steps 1: 1.) NaHCO3, 2.) LiOH / 1.) H2O, dioxane, ice/NaCl bath; 2.) ethyl acetate, 0.05 M LiOH 2: 46 percent / hexamethylphosphoric acid triamide / 3 h / Ambient temperature View Scheme

thienamycin (59995-64-1) → p-nitrobenzyl (3S,5S,6S)-2-<<2-<<<(p-nitrobenzyl)oxy>carbonyl>amino>ethyl>thio>-6-<(R)-1-hydroxyethyl>carbapen-1-em-3-carboxylate (72778-08-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) NaHCO3, 2.) LiOH / 1.) H2O, dioxane, 10 min, 2.) EtOAc 2: HMPA / 2.5 h / Ambient temperature 3: 24 percent / 1,5-diazabicyclo<5.4.0>ondec-5-ene / dimethylsulfoxide / 0.17 h / Ambient temperature View Scheme
Multi-step reaction with 3 steps 1: 1.) NaHCO3, 2.) LiOH / 1.) H2O, dioxane, ice/NaCl bath; 2.) ethyl acetate, 0.05 M LiOH 2: 46 percent / hexamethylphosphoric acid triamide / 3 h / Ambient temperature 3: 21 percent / DBU / dimethylsulfoxide / 0.5 h View Scheme

thienamycin (59995-64-1) → Δ1-thienamycin (77171-32-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: 1.) NaHCO3, 2.) LiOH / 1.) H2O, dioxane, 10 min, 2.) EtOAc 2: HMPA / 2.5 h / Ambient temperature 3: 24 percent / 1,5-diazabicyclo<5.4.0>ondec-5-ene / dimethylsulfoxide / 0.17 h / Ambient temperature 4: 63 percent / H2 / 10percent Pd/c / tetrahydrofuran; ethanol / 0.5 h / Ambient temperature; phosphate buffer pH 7 View Scheme

thienamycin (59995-64-1) → 3-Hydroxy-5-[(1S,2R)-2-hydroxy-1-(morpholine-4-carbonyl)-propyl]-1H-pyrrole-2-carboxylic acid 4-nitro-benzyl ester

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) NaHCO3, 2.) LiOH / 1.) H2O, dioxane, 10 min, 2.) EtOAc 2: HMPA / 2.5 h / Ambient temperature 3: 2.1 mg / tetrahydrofuran / 96 h / Ambient temperature View Scheme

thienamycin (59995-64-1) → (2S,5S,6S)-3-[2-(4-Nitro-benzyloxycarbonylamino)-ethylsulfanyl]-6-[(R)-1-(4-nitro-benzyloxycarbonyloxy)-ethyl]-7-oxo-1-aza-bicyclo[3.2.0]hept-3-ene-2-carboxylic acid 4-nitro-benzyl ester (72843-08-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: 1.) NaHCO3, 2.) LiOH / 1.) H2O, dioxane, ice/NaCl bath; 2.) ethyl acetate, 0.05 M LiOH 2: 46 percent / hexamethylphosphoric acid triamide / 3 h / Ambient temperature 3: 21 percent / DBU / dimethylsulfoxide / 0.5 h 4: 49 percent / 4-(dimethylamino)pyridine / CH2Cl2 / 2.5 h / Ambient temperature View Scheme

thienamycin (59995-64-1) → N-<<(p-nitrobenzyl)oxy>carbonyl>-O-<<(p-nitrobenzyl)oxy>carbonyl>thienamycin p-nitrobenzyl ester (72778-09-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) NaHCO3, 2.) LiOH / 1.) H2O, dioxane, ice/NaCl bath; 2.) ethyl acetate, 0.05 M LiOH 2: 46 percent / hexamethylphosphoric acid triamide / 3 h / Ambient temperature 3: 58 percent / 4-(dimethylamino)pyridine / CH2Cl2 / 2.5 h / Ambient temperature View Scheme

Upstream product

• 3473-63-0 formamidine acetic acid 
• 118334-32-0 imipenem 
• 75321-07-2 (3S,4R)-3-[(R)-1-hydroxyethyl]-4-[3-(4-nitrobenzyl)-oxycarbonyl-2-oxopropyl]azetidin-2-one 
• 74288-39-4 (3S,4R)-3-[(R)-1-hydroxyethyl)-4-[3-(4-nitrobenzyl)oxycarbonyl-2-oxo-3-diazopropyl]azetidin-2-one 
• 75321-05-0 (3S,4R)-1-(tert-Butyldimethylsilyl)-3-<(1R)-1-hydroxyethyl>-4-(carboxymethyl)azetidin-2-one 
• 75321-01-6 (S)-1-(tert-Butyl-dimethyl-silanyl)-4-(2-trimethylsilanyl-[1,3]dithian-2-ylmethyl)-azetidin-2-one 
• 75321-04-9 (3S,4R)-1-(t-butyldimethylsilyl)-3-[(R)-1-hydroxyethyl]-4-(2-oxo-2-trimethylsilylethyl)-azetidin-2-one 
• 75333-88-9 (3S,4R)-1-(tert-Butyl-dimethyl-silanyl)-3-((R)-1-hydroxy-ethyl)-4-(2-imidazol-1-yl-2-oxo-ethyl)-azetidin-2-one 
• 77551-48-5 (3S,4R)-3-Acetyl-1-(tert-butyl-dimethyl-silanyl)-4-(2-trimethylsilanyl-[1,3]dithian-2-ylmethyl)-azetidin-2-one 
• 75321-06-1 (3S,4R)-1-(t-butyldimethylsilyl)-3-[(R)-1-hydroxyethyl]-4-(3-p-nitrobenzyloxycarbonyl-2-oxopropyl)-azetidin-2-one 
• 75321-02-7 (3S,4R)-1-(tert-Butyl-dimethyl-silanyl)-3-(1-hydroxy-ethyl)-4-(2-trimethylsilanyl-[1,3]dithian-2-ylmethyl)-azetidin-2-one 
• 75321-02-7 (3S,4R)-1-(tert-Butyl-dimethyl-silanyl)-3-((R)-1-hydroxy-ethyl)-4-(2-trimethylsilanyl-[1,3]dithian-2-ylmethyl)-azetidin-2-one 
• 78963-60-7 (3R,4R)-4-acetoxy-3-<(S)-1-(tert-butyldimethylsilyloxy)ethyl>-2-azetidinone 
• 102046-01-5 (2S,3S)-1-(tert-Butyl-dimethyl-silanyl)-3-[(S)-1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-4-oxo-azetidine-2-carbaldehyde 

Downstream Products

• 694-85-9 1-methyl-2-pyridone 
• 77660-71-0 C₂₃H₂₅N₃O₄S 
• 64066-86-0 N-<<(p-nitrobenzyl)oxy>carbonyl>thienamycin lithium salt 
• 72843-08-4 (2S,5S,6S)-3-[2-(4-Nitro-benzyloxycarbonylamino)-ethylsulfanyl]-6-[(R)-1-(4-nitro-benzyloxycarbonyloxy)-ethyl]-7-oxo-1-aza-bicyclo[3.2.0]hept-3-ene-2-carboxylic acid 4-nitro-benzyl ester 
• 72778-09-7 N-<<(p-nitrobenzyl)oxy>carbonyl>-O-<<(p-nitrobenzyl)oxy>carbonyl>thienamycin p-nitrobenzyl ester 
• 77171-32-5 Δ¹-thienamycin 
• 72778-08-6 p-nitrobenzyl (3S,5S,6S)-2-<<2-<<<(p-nitrobenzyl)oxy>carbonyl>amino>ethyl>thio>-6-<(R)-1-hydroxyethyl>carbapen-1-em-3-carboxylate 
• 64067-13-6 p-nitrobenzyl (5R,6S)-2-<<2-<<<(p-nitrobenzyl)oxy>carbonyl>amino>ethyl>thio>-6-<(R)-1-hydroxyethyl>carbapen-2-em-3-carboxylate 

Relevant articles and documents

Antibiotic synthesis

A method of preparing intermediates for carbapenem antibiotics characterized by treating a N-deprotected acetoxy conpound of the formula: STR1 in the presence of a Lewis acid or a silylating agent to yeild an intermediate; and cyclizing the intermediate in the presence of rhodium (II) acetate to form a bicyclic ketoester.

Stability and kinetics of degradation of imipenem in aqueous solution

In weakly acidic solution, the broad-spectrum antibiotic imipenem undergoes complex oligomerization initiated by intermolecular carboxyl group attack on the β-lactam group. In weakly alkaline solution, intermolecular reaction between the β-lactam and formimidoyl groups occurs instead. Both β-lactam and formimidoyl groups also hydrolyze at pH-dependent rates. Complex decomposition schemes were determined in kinetic studies at pH 4.0 and 9.0-9.5 using HPLC and mathematical models. The rates of the several initial reactions, calculated as functions of pH and imipenem concentration by fitting the models to kinetic data, fully account for imipenem decomposition rates throughout the neutral pH range.

N-acyl derivatives of thienamycin

Disclosed are N-acyl derivatives of the antibiotic thienamycin having the following structural formula: STR1 wherein R1 and R2 are independently selected from the group consisting of hydrogen and acyl. Such derivatives and their pharmaceutically acceptable salts, are useful as antibiotics. Also disclosed are processes for the preparation of such derivatives, pharmaceutical compositions comprising such derivatives, and methods of treatment comprising administering such derivatives and compositions when an antibiotic effect is indicated.

Salts of amino-beta-lactamic acids and process for the preparation thereof

Amino-beta-lactamic acid salts, having the formula: STR1 wherein: (X-Y) may form a system having from 1 to 3 carbon atoms, with or without double bond, (a) closed, in which: X is an atom selected from among carbon, oxygen, nitrogen and sulphur; Y is methylene; Z is a carboxy, sulphonic or phosphonic group (b) open, which may comprise a double bond, in which: X is an atom of hydrogen or a methyl, hydroxymethyl or thiol group, Y is an acid radical chosen from the group formed by sulphonic, phosphonic and sulphoamidic acid; Z is missing. R is an atom or hydrogen, or a methoxyl or ethoxyl group. R1 is, when present, methyl, acetoxymethyl, acylthiomethyl, such as acetyl and benzoyl derivatives, methoxy, chlorine, carbamoyloxymethyl, azido, azidomethyl (alpha, beta)-thioethylamine or a thiomethyl-heterocyclic derivative of the thiazole, thiadiazole, triazole, tetrazole, oxazole, oxadiazole, pyrimidine and imidazole nuclei. R2 is an atom of hydrogen or a methyl, ethyl, benzyl or phenyl group. m, n may be the same or different and may range from 1 to 4, forming a ring or m=n=O to form an open chain. A process for their preparation is also disclosed.

AN ENANTIOSELECTIVE APPROACH TO CARBAPENEM ANTIBIOTICS: FORMAL SYNTHESIS OF (+)-THIENAMYCIN

An enantioselective synthesis of intermediates in synthesis of thienamycin (15) and epithienamycin-C (16) is described.

3-[1-Hydroxyethyl]-4-carboxymethyl-azetidin-2-one

In a process for the total synthesis of thienamycin from L-aspartic acid via intermediate III: STR1 there is disclosed a process for preparing III via STR2 wherein R is a protecting group.

Process for the preparation of 1-carbapenems and intermediates via trithioorthoacetates

Disclosed is a process for the total synthesis of 1-carbapenem antibiotics (I) from L-aspartic acid via intermediates II and III: STR1 wherein R is hydrogen, a pharmaceutically acceptable ester moiety or salt cation, or a readily removable blocking group; R6 and R7 are, inter alia, independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl and aralkyl; R1' is hydrogen or a protecting group; and Ra, Rb and Rc are independently selected from alkyl, aryl and aralkyl.

Process for the preparation of (2S)-tetrahydro-2α-methyl-6-oxo-4βα-carboxylic acid

Disclosed is a process for preparing (2S)-tetrahydro-2α-methyl-6-oxo-4β-amino-2H-pyran-3α-carboxylic acid (I) which is useful in the synthesis of thienamycin. The process proceeds via a stereospecific reduction of the 2-acetyl-3-(R)-α-methylbenzylamino-2-pentenedioic acid diester (II). STR1 wherein R is, α-methylbenzyl, and R1 is lower alkyl having 1-6 carbon atoms or arylalkyl such as benzyl.

Process for the preparation of thienamycin and intermediates

Disclosed is a process for the total synthesis of thienamycin from 4-allylazetidinone (IIIa) via STR1 L-aspartic acid (III): STR2 R=H, blocking group or salt cation.