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
• Article Data: 12

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

Thienamycin is one of the most potent naturally produced antibiotics known thus far. It has excellent activity against both Gram-positive and Gram-negative bacteria and is resistant to bacterial β-lactamase enzymes.

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

• 82938-51-0 C₁₂H₂₃NO₄Si 
• 82938-51-0 (2S,3S)-1-(tert-Butyl-dimethyl-silanyl)-3-(1-hydroxy-ethyl)-4-oxo-azetidine-2-carboxylic acid 
• 82938-52-1 (2S,3S)-3-Acetyl-1-(tert-butyl-dimethyl-silanyl)-4-oxo-azetidine-2-carboxylic acid 
• 87037-95-4 (3R,4R)-4-acetoxy-3-[(1R)-1-hydroxyethyl]azetidin-2-one 
• 102046-00-4 (3S,4S)-1-(tert-Butyl-dimethyl-silanyl)-3-[(S)-1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-4-((E)-styryl)-azetidin-2-one 
• 102045-99-8 (3S,4R)-1-(tert-Butyl-dimethyl-silanyl)-3-[(S)-1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-4-((E)-styryl)-azetidin-2-one 
• 101977-83-7 (1'S,3S,4S)-3-(1'-<(tert-butyldimethylsilyl)oxy>ethyl)-1-(4'-methoxyphenyl)-4-(2'-phenylethenyl)-2-azetidinone 
• 101977-77-9 <3S,4S(E)>-3-<1(S)-hydroxyethyl>-1-(4-methoxyphenyl)-4-(2-phenylethenyl)-2-azetidinone 
• 102129-90-8 (2R,3S)-1-(tert-Butyl-dimethyl-silanyl)-3-[(S)-1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-4-oxo-azetidine-2-carboxylic acid 
• 102129-88-4 (2S,3S)-1-(tert-Butyl-dimethyl-silanyl)-3-[(S)-1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-4-oxo-azetidine-2-carboxylic acid 
• 102129-89-5 (2R,3S)-1-(tert-Butyl-dimethyl-silanyl)-3-[(S)-1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-4-oxo-azetidine-2-carbaldehyde 
• 102046-01-5 (2S,3S)-1-(tert-Butyl-dimethyl-silanyl)-3-[(S)-1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-4-oxo-azetidine-2-carbaldehyde 
• 78963-60-7 (3R,4R)-4-acetoxy-3-<(S)-1-(tert-butyldimethylsilyloxy)ethyl>-2-azetidinone 
• 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 

Downstream Products

• 694-85-9 1-methyl-2-pyridone 
• 77660-71-0 C₂₃H₂₅N₃O₄S 
• 64066-86-0 N-<<(p-nitrobenzyl)oxy>carbonyl>thienamycin lithium salt 
• 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 
• 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 
• 77171-32-5 Δ¹-thienamycin 
• 72778-09-7 N-<<(p-nitrobenzyl)oxy>carbonyl>-O-<<(p-nitrobenzyl)oxy>carbonyl>thienamycin p-nitrobenzyl ester 
• 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 

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.

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.

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.