180973-24-4

Basic information

• Product Name: (3S,4E)-3-Hydroxy-7-[(triphenylmethyl)thio]-4-heptenoic acid
• Synonyms: (3S,4E)-3-Hydroxy-7-[(triphenylmethyl)thio]-4-heptenoic acid;(S,E)-3-hydroxy-7-(tritylthio)hept-4-enoic acid;4-Heptenoic acid, 3-hydroxy-7-[(triphenylMethyl)thio]-, (3S,4E)-;(3S,4E)-3-Hydroxy-7-[(triphenylMethyl)thio]-4-heptenoic;(3S)-3-hydroxy-7-tritylsulfanylhept-4-enoic acid;(E,3S)-3-hydroxy-7-tritylsulfanyl-hept-4-enoic acid
• CAS NO: 180973-24-4
• Molecular Formula: C₂₆H₂₆O₃S
• Molecular Weight: 418.554
• Mol File: 180973-24-4.mol
• Article Data: 7

Chemical Properties

• Appearance: /
• Density: 1.201
• CAS DataBase Reference: (3S,4E)-3-Hydroxy-7-[(triphenylmethyl)thio]-4-heptenoic acid(CAS DataBase Reference)
• NIST Chemistry Reference: (3S,4E)-3-Hydroxy-7-[(triphenylmethyl)thio]-4-heptenoic acid(180973-24-4)
• EPA Substance Registry System: (3S,4E)-3-Hydroxy-7-[(triphenylmethyl)thio]-4-heptenoic acid(180973-24-4)

Safety Data

• Hazardous Substances Data: 180973-24-4(Hazardous Substances Data)

Usage

General Description

The chemical compound "(3S,4E)-3-Hydroxy-7-[(triphenylmethyl)thio]-4-heptenoic acid" is a thioester derivative of a six-carbon unsaturated fatty acid. It contains a hydroxyl group at the third carbon, a thioether linkage with a triphenylmethyl group at the seventh carbon, and a double bond in the E-configuration at the fourth carbon. (3S,4E)-3-Hydroxy-7-[(triphenylmethyl)thio]-4-heptenoic acid is likely to possess biological activity due to its structural similarity to endogenous lipid molecules and may be of interest for studying lipid metabolism or developing therapeutics targeting thioesterases or other enzymes involved in fatty acid metabolism. Further research is needed to fully understand the properties and potential applications of this compound.

Synthetic route

(E)-(S)-3-Hydroxy-7-tritylsulfanyl-hept-4-enoic acid benzyl ester (180973-40-4) → (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4)

Conditions	Yield
With lithium hydroxide In methanol; water	100%

(3S,4E)-3-hydroxy-1-((4R)-4-isopropyl-2-thioxothiazolidin-3-yl)-7-tritylsulfanyl-hept-4-en-1-one (663918-95-4) → (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4)

Conditions	Yield
With lithium hydroxide; water In tetrahydrofuran Cooling with ice;	96%
Stage #1: (3S,4E)-3-hydroxy-1-((4R)-4-isopropyl-2-thioxothiazolidin-3-yl)-7-tritylsulfanyl-hept-4-en-1-one With water; lithium hydroxide In tetrahydrofuran at 0 - 20℃; Stage #2: With hydrogenchloride In tetrahydrofuran; water pH=2;	86%
With lithium hydroxide monohydrate; water In tetrahydrofuran at 0 - 30℃; for 12h;	13 g

(E)-(S)-3-hydroxy-1-[(R)-4-isopropyl-5,5-diphenyl-2-oxo-oxazolidin-3-yl]-7-tritylthio-4-hepten-1-one (878630-47-8) → (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4)

Conditions	Yield
Stage #1: (E)-(S)-3-hydroxy-1-[(R)-4-isopropyl-5,5-diphenyl-2-oxo-oxazolidin-3-yl]-7-tritylthio-4-hepten-1-one With water; sodium hydroxide In tetrahydrofuran; methanol at 0℃; for 1h; Stage #2: With hydrogenchloride In water; ethyl acetate at 0℃;	92%
With sodium hydroxide	76%
With sodium hydroxide In methanol; water at 0 - 20℃; for 1h;	58%

(2E)-5-[(triphenylmethyl)thio]-2-pentenal (180973-22-2) → (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: BuLi / tetrahydrofuran / -78 °C 1.2: Cp2ZrCl2 / tetrahydrofuran / -78 - 20 °C 2.1: 76 percent / NaOH View Scheme
Multi-step reaction with 2 steps 1.1: SmI2 / tetrahydrofuran / -78 °C 1.2: tetrahydrofuran / -78 °C 2.1: 76 percent / NaOH View Scheme
Multi-step reaction with 2 steps 1: 99 percent / Ti(IV) complex with (S)-(-)-binaphthyl amino alcohol 2: 100 percent / LiOH / methanol; H2O View Scheme

triphenylmethanethiol (3695-77-0) → (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4)

Conditions	Yield
Multi-step reaction with 5 steps 1: 78 percent / Cs2CO3 2: 91 percent / DIBAL 3: 74 percent / (COCl)2, DMSO, Et3N 4: 99 percent / Ti(IV) complex with (S)-(-)-binaphthyl amino alcohol 5: 100 percent / LiOH / methanol; H2O View Scheme
Multi-step reaction with 4 steps 1.1: triethylamine / dichloromethane / 1 h / 25 °C / Inert atmosphere; Automated synthesizer 2.1: dmap / N,N-dimethyl-formamide / 2 h / 100 °C / Inert atmosphere; Automated synthesizer 2.2: 2 h / -20 - 25 °C / Inert atmosphere; Automated synthesizer 2.3: -78 - 0 °C / Inert atmosphere; Automated synthesizer 3.1: n-butyllithium / tetrahydrofuran; hexane / 1 h / -78 °C / Inert atmosphere; Automated synthesizer 3.2: 1 h / -78 - -30 °C / Inert atmosphere; Automated synthesizer 3.3: 1 h / -50 - 0 °C / Inert atmosphere; Automated synthesizer 4.1: water; sodium hydroxide / tetrahydrofuran; methanol / 1 h / 0 °C 4.2: 0 °C View Scheme
Multi-step reaction with 4 steps 1.1: sodium hydride / tetrahydrofuran / 20 °C / Flow reactor 2.1: diisobutylaluminium hydride / toluene / -97 °C / Flow reactor 3.1: lithium hexamethyldisilazane / tetrahydrofuran / -40 °C / Flow reactor 3.2: 0.02 h / -78 °C / Flow reactor 4.1: sodium hydroxide / methanol; water / 1 h / 0 - 20 °C View Scheme

(E)-5-(tritylthio)-2-penten-1-ol (180973-37-9) → (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: 74 percent / (COCl)2, DMSO, Et3N 2: 99 percent / Ti(IV) complex with (S)-(-)-binaphthyl amino alcohol 3: 100 percent / LiOH / methanol; H2O View Scheme
Multi-step reaction with 3 steps 1.1: manganese(IV) oxide / dichloromethane / 8 h / 25 - 45 °C 2.1: titanium tetrachloride / dichloromethane / 0 - 5 °C 2.2: 2 h / -78 °C 2.3: 0.5 h / -78 °C 3.1: lithium hydroxide monohydrate; water / tetrahydrofuran / 12 h / 0 - 30 °C View Scheme

(E)-5-Tritylsulfanyl-pent-2-enoic acid methyl ester (180973-36-8) → (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: 91 percent / DIBAL 2: 74 percent / (COCl)2, DMSO, Et3N 3: 99 percent / Ti(IV) complex with (S)-(-)-binaphthyl amino alcohol 4: 100 percent / LiOH / methanol; H2O View Scheme

methyl (2E)-penta-2,4-dienoate (2409-87-2) → (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4)

Conditions	Yield
Multi-step reaction with 5 steps 1: 78 percent / Cs2CO3 2: 91 percent / DIBAL 3: 74 percent / (COCl)2, DMSO, Et3N 4: 99 percent / Ti(IV) complex with (S)-(-)-binaphthyl amino alcohol 5: 100 percent / LiOH / methanol; H2O View Scheme

S-trityl 3-mercaptopropionaldehyde (150350-28-0) → (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: dmap / N,N-dimethyl-formamide / 2 h / 100 °C / Inert atmosphere; Automated synthesizer 1.2: 2 h / -20 - 25 °C / Inert atmosphere; Automated synthesizer 1.3: -78 - 0 °C / Inert atmosphere; Automated synthesizer 2.1: n-butyllithium / tetrahydrofuran; hexane / 1 h / -78 °C / Inert atmosphere; Automated synthesizer 2.2: 1 h / -78 - -30 °C / Inert atmosphere; Automated synthesizer 2.3: 1 h / -50 - 0 °C / Inert atmosphere; Automated synthesizer 3.1: water; sodium hydroxide / tetrahydrofuran; methanol / 1 h / 0 °C 3.2: 0 °C View Scheme
Multi-step reaction with 4 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 0 °C / Inert atmosphere 1.2: 0 - 20 °C / Inert atmosphere 2.1: diisobutylaluminium hydride / toluene / -97 °C / Flow reactor 3.1: lithium hexamethyldisilazane / tetrahydrofuran / -40 °C / Flow reactor 3.2: 0.02 h / -78 °C / Flow reactor 4.1: sodium hydroxide / methanol; water / 1 h / 0 - 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 0 °C / Inert atmosphere 1.2: 0 - 20 °C / Inert atmosphere 2.1: diisobutylaluminium hydride / toluene / -97 °C / Flow reactor 3.1: lithium hexamethyldisilazane / tetrahydrofuran / -78 °C / Flow reactor 3.2: 0.02 h / Flow reactor 4.1: sodium hydroxide / methanol; water / 1 h / 0 - 20 °C View Scheme
Multi-step reaction with 5 steps 1.1: triphenylphosphine / toluene; water / 6 h / 25 - 105 °C 1.2: 2 h / 0 - 5 °C 2.1: diisobutylaluminium hydride / toluene / 3 h / 0 - 5 °C / Inert atmosphere 3.1: manganese(IV) oxide / dichloromethane / 8 h / 25 - 45 °C 4.1: titanium tetrachloride / dichloromethane / 0 - 5 °C 4.2: 2 h / -78 °C 4.3: 0.5 h / -78 °C 5.1: lithium hydroxide monohydrate; water / tetrahydrofuran / 12 h / 0 - 30 °C View Scheme

ethyl (E)-5-(triphenylmethylthio)-2-pentenoate (1309766-86-6) → (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: diisobutylaluminium hydride / toluene / -97 °C / Flow reactor 2.1: lithium hexamethyldisilazane / tetrahydrofuran / -40 °C / Flow reactor 2.2: 0.02 h / -78 °C / Flow reactor 3.1: sodium hydroxide / methanol; water / 1 h / 0 - 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: diisobutylaluminium hydride / toluene / -97 °C / Flow reactor 2.1: lithium hexamethyldisilazane / tetrahydrofuran / -78 °C / Flow reactor 2.2: 0.02 h / Flow reactor 3.1: sodium hydroxide / methanol; water / 1 h / 0 - 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: diisobutylaluminium hydride / toluene / 3 h / 0 - 5 °C / Inert atmosphere 2.1: manganese(IV) oxide / dichloromethane / 8 h / 25 - 45 °C 3.1: titanium tetrachloride / dichloromethane / 0 - 5 °C 3.2: 2 h / -78 °C 3.3: 0.5 h / -78 °C 4.1: lithium hydroxide monohydrate; water / tetrahydrofuran / 12 h / 0 - 30 °C View Scheme

trityl chloride (76-83-5) → (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4)

Conditions

Yield

Multi-step reaction with 8 steps 1.1: toluene / 6 h / 25 - 30 °C 2.1: sodium tetrahydroborate / tetrahydrofuran / 0.17 h / 0 - 5 °C 2.2: 3 h / 0 - 30 °C 3.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 2 h / -75 - -70 °C 3.2: 2 h / -75 - 5 °C 4.1: triphenylphosphine / toluene; water / 6 h / 25 - 105 °C 4.2: 2 h / 0 - 5 °C 5.1: diisobutylaluminium hydride / toluene / 3 h / 0 - 5 °C / Inert atmosphere 6.1: manganese(IV) oxide / dichloromethane / 8 h / 25 - 45 °C 7.1: titanium tetrachloride / dichloromethane / 0 - 5 °C 7.2: 2 h / -78 °C 7.3: 0.5 h / -78 °C 8.1: lithium hydroxide monohydrate; water / tetrahydrofuran / 12 h / 0 - 30 °C View Scheme

3-(tritylthio) propanoic acid (27144-18-9) → (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4)

Conditions

Yield

Multi-step reaction with 7 steps 1.1: sodium tetrahydroborate / tetrahydrofuran / 0.17 h / 0 - 5 °C 1.2: 3 h / 0 - 30 °C 2.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 2 h / -75 - -70 °C 2.2: 2 h / -75 - 5 °C 3.1: triphenylphosphine / toluene; water / 6 h / 25 - 105 °C 3.2: 2 h / 0 - 5 °C 4.1: diisobutylaluminium hydride / toluene / 3 h / 0 - 5 °C / Inert atmosphere 5.1: manganese(IV) oxide / dichloromethane / 8 h / 25 - 45 °C 6.1: titanium tetrachloride / dichloromethane / 0 - 5 °C 6.2: 2 h / -78 °C 6.3: 0.5 h / -78 °C 7.1: lithium hydroxide monohydrate; water / tetrahydrofuran / 12 h / 0 - 30 °C View Scheme

3-(tritylthio)propan-1-ol (100360-56-3) → (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 2 h / -75 - -70 °C 1.2: 2 h / -75 - 5 °C 2.1: triphenylphosphine / toluene; water / 6 h / 25 - 105 °C 2.2: 2 h / 0 - 5 °C 3.1: diisobutylaluminium hydride / toluene / 3 h / 0 - 5 °C / Inert atmosphere 4.1: manganese(IV) oxide / dichloromethane / 8 h / 25 - 45 °C 5.1: titanium tetrachloride / dichloromethane / 0 - 5 °C 5.2: 2 h / -78 °C 5.3: 0.5 h / -78 °C 6.1: lithium hydroxide monohydrate; water / tetrahydrofuran / 12 h / 0 - 30 °C View Scheme

(S)-2-{(Z)-2-[(S)-2-((R)-2-Amino-3-methyl-butyrylamino)-3-tritylsulfanyl-propionylamino]-but-2-enoylamino}-3-methyl-butyric acid methyl ester (180973-32-4) + (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4) → (5E,7S,11R,14S,17E,20S)-methyl 17-ethylidene-7-hydroxy-11,20-diisopropyl-9,12,15,18-tetraoxo-1,1,1-triphenyl-14-(tritylthiomethyl)-2-thia-10,13,16,19-tetraazahenicos-5-en-21-oate (180973-33-5)

Conditions	Yield
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine	95%

C52H49N5O7S (1196992-63-8) + (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4) → C63H63N5O7S2 (1196992-65-0)

Conditions	Yield
Stage #1: C52H49N5O7S With diethylamine In acetonitrile at 20℃; for 2h; Inert atmosphere; Stage #2: (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane; acetonitrile at 0 - 20℃; Inert atmosphere;	95%

(R)-4-(9H-fluoren-9-ylmethoxycarbonylamino)-4-{(S)-1-[1-(methoxycarbonylmethyl-carbamoyl)-cyclopropylcarbamoyl]-2-tritylsulfanyl-ethylcarbamoyl}-butyric acid tert-butyl ester (1196992-16-1) + (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4) → (R)-4-((E)-(S)-3-hydroxy-7-tritylsulfanyl-hept-4-enoylamino)-4-{(S)-1-[1-(methoxycarbonylmethyl-carbamoyl)-cyclopropylcarbamoyl]-2-tritylsulfanyl-ethylcarbamoyl}-butyric acid tert-butyl ester (1196992-18-3)

Conditions

Yield

Stage #1: (R)-4-(9H-fluoren-9-ylmethoxycarbonylamino)-4-{(S)-1-[1-(methoxycarbonylmethyl-carbamoyl)-cyclopropylcarbamoyl]-2-tritylsulfanyl-ethylcarbamoyl}-butyric acid tert-butyl ester With diethylamine In acetonitrile at 20℃; for 1h; Stage #2: (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane; acetonitrile at 0 - 20℃;

91%

[(1-{(S)-2-[(R)-2-(9H-Fluoren-9-ylmethoxycarbonylamino)-3-phenyl-propionylamino]-3-tritylsulfanyl-propionylamino}-cyclopropanecarbonyl)-amino]-acetic acid methyl ester (1196992-76-3) + (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4) → [(1-{(S)-2-[(R)-2-((E)-(S)-3-hydroxy-7-tritylsulfanyl-hept-4-enoylamino)-3-phenyl-propionylamino]-3-tritylsulfanyl-propionylamino}-cyclopropanecarbonyl)-amino]-acetic acid methyl ester (1196992-77-4)

Conditions

Yield

Stage #1: [(1-{(S)-2-[(R)-2-(9H-Fluoren-9-ylmethoxycarbonylamino)-3-phenyl-propionylamino]-3-tritylsulfanyl-propionylamino}-cyclopropanecarbonyl)-amino]-acetic acid methyl ester With diethylamine In acetonitrile at 20℃; for 2h; Inert atmosphere; Stage #2: (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane; acetonitrile at 0 - 20℃; Inert atmosphere;

87%

(R)-4-(9H-fluoren-9-ylmethoxycarbonylamino)-4-{(S)-1-[1-(methoxycarbonylmethyl-carbamoyl)-1-methyl-ethylcarbamoyl]-2-tritylsulfanyl-ethylcarbamoyl}-butyric acid tert-butyl ester (1196992-05-8) + (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4) → (R)-4-((E)-(S)-3-hydroxy-7-tritylsulfanyl-hept-4-enoylamino)-4-{(S)-1-[1-(methoxycarbonylmethyl-carbamoyl)-1-methyl-ethylcarbamoyl]-2-tritylsulfanyl-ethylcarbamoyl}-butyric acid tert-butyl ester (1196992-07-0)

Conditions

Yield

Stage #1: (R)-4-(9H-fluoren-9-ylmethoxycarbonylamino)-4-{(S)-1-[1-(methoxycarbonylmethyl-carbamoyl)-1-methyl-ethylcarbamoyl]-2-tritylsulfanyl-ethylcarbamoyl}-butyric acid tert-butyl ester With diethylamine In acetonitrile at 20℃; Stage #2: (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane; acetonitrile at 0 - 20℃;

85%

2-(Trimethylsilyl)ethanol (2916-68-9) + (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4) → (S,E)-2-(trimethylsilyl)ethyl 3-(((S)-2-amino-3-methylbutanoyl)oxy)-7-(tritylthio)hept-4-enoate (1043577-31-6)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane Cooling with ice;	80%
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0 - 5℃; for 0.916667h;	2.5 g

[(1-{(S)-2-[(R)-3-(3-chloro-phenyl)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-propionylamino]-3-tritylsulfanyl-propionylamino}-cyclopropanecarbonyl)-amino]-acetic acid methyl ester (1196992-69-4) + (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4) → [(1-{(S)-2-[(R)-3-(3-chloro-phenyl)-2-((E)-(S)-3-hydroxy-7-tritylsulfanyl-hept-4-enoylamino)-propionylamino]-3-tritylsulfanyl-propionylamino}-cyclopropanecarbonyl)-amino]-acetic acid methyl ester (1196992-72-9)

Conditions

Yield

Stage #1: [(1-{(S)-2-[(R)-3-(3-chloro-phenyl)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-propionylamino]-3-tritylsulfanyl-propionylamino}-cyclopropanecarbonyl)-amino]-acetic acid methyl ester With diethylamine In dichloromethane; acetonitrile at 20℃; for 1.5h; Inert atmosphere; Stage #2: (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane; acetonitrile at 20℃; for 16h; Inert atmosphere;

80%

(R)-4-(9H-fluoren-9-ylmethoxycarbonylamino)-4-{(S)-1-[1-(methoxycarbonylmethyl-carbamoyl)-cyclobutylcarbamoyl]-2-tritylsulfanyl-ethylcarbamoyl}-butyric acid tert-butyl ester (1196992-35-4) + (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4) → (R)-4-((E)-(S)-3-hydroxy-7-tritylsulfanyl-hept-4-enoylamino)-4-{(S)-1-[1-(methoxycarbonylmethyl-carbamoyl)-cyclobutylcarbamoyl]-2-tritylsulfanyl-ethylcarbamoyl}-butyric acid tert-butyl ester (1196992-37-6)

Conditions

Yield

Stage #1: (R)-4-(9H-fluoren-9-ylmethoxycarbonylamino)-4-{(S)-1-[1-(methoxycarbonylmethyl-carbamoyl)-cyclobutylcarbamoyl]-2-tritylsulfanyl-ethylcarbamoyl}-butyric acid tert-butyl ester With diethylamine In acetonitrile at 20℃; Inert atmosphere; Stage #2: (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane; acetonitrile at 0 - 20℃; Inert atmosphere;

75%

(R)-4-(9H-fluoren-9-ylmethoxycarbonylamino)-4-{(S)-1-[1-(1-hydroxy-2-methoxycarbonyl-ethyl)-cyclopropylcarbamoyl]-2-tritylsulfanyl-ethylcarbamoyl}-butyric acid tert-butyl ester (1196991-91-9) + (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4) → (R)-4-{(S)-1-[1-(1-hydroxy-2-methoxycarbonyl-ethyl)-cyclopropylcarbamoyl]-2-tritylsulfanyl-ethylcarbamoyl}-4-((E)-(S)-3-hydroxy-7-tritylsulfanyl-hept-4-enoylamino)-butyric acid tert-butyl ester (1196991-93-1)

Conditions

Yield

Stage #1: (R)-4-(9H-fluoren-9-ylmethoxycarbonylamino)-4-{(S)-1-[1-(1-hydroxy-2-methoxycarbonyl-ethyl)-cyclopropylcarbamoyl]-2-tritylsulfanyl-ethylcarbamoyl}-butyric acid tert-butyl ester With diethylamine In dichloromethane; acetonitrile for 1.5h; Stage #2: (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 16h; Inert atmosphere;

72%

(3S,4R)-4-[(S)-2-((R)-2-Amino-propionylamino)-3-tritylsulfanyl-propionylamino]-3-hydroxy-5-methyl-hexanoic acid allyl ester + (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4) → (3S,4R)-3-Hydroxy-4-{(S)-2-[(R)-2-((E)-(S)-3-hydroxy-7-tritylsulfanyl-hept-4-enoylamino)-propionylamino]-3-tritylsulfanyl-propionylamino}-5-methyl-hexanoic acid allyl ester (881845-29-0)

Conditions	Yield
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine	65%

[(1-{(S)-2-[(R)-2-(9H-Fluoren-9-ylmethoxycarbonylamino)-3-pyridin-4-yl-propionylamino]-3-tritylsulfanyl-propionylamino}-cyclopropanecarbonyl)-amino]-acetic acid methyl ester (1196992-82-1) + (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4) → [(1-{(S)-2-[(R)-2-((E)-(S)-3-hydroxy-7-tritylsulfanyl-hept-4-enoylamino)-3-pyridin-4-yl-propionylamino]-3-tritylsulfanyl-propionylamino}-cyclopropanecarbonyl)-amino]-acetic acid methyl ester (1196992-84-3)

Conditions

Yield

Stage #1: [(1-{(S)-2-[(R)-2-(9H-Fluoren-9-ylmethoxycarbonylamino)-3-pyridin-4-yl-propionylamino]-3-tritylsulfanyl-propionylamino}-cyclopropanecarbonyl)-amino]-acetic acid methyl ester With diethylamine In acetonitrile at 20℃; Inert atmosphere; Stage #2: (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane; acetonitrile at 0 - 20℃; Inert atmosphere;

61%

C46H44N4O7S (1196992-56-9) + (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4) → [(1-{(S)-2-[2-((E)-(S)-3-hydroxy-7-tritylsulfanyl-hept-4-enoylamino)-acetylamino]-3-tritylsulfanyl-propionylamino}-cyclopropanecarbonyl)-amino]-acetic acid methyl ester (1196992-58-1)

Conditions	Yield
Stage #1: C46H44N4O7S With diethylamine In acetonitrile at 20℃; for 2h; Inert atmosphere; Stage #2: (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane; acetonitrile at 20℃; for 16h; Inert atmosphere;	56%

((R)-2-{(S)-2-[2-(9H-Fluoren-9-ylmethoxycarbonylamino)-2-methyl-propionylamino]-3-tritylsulfanyl-propionylamino}-3-methyl-butyrylamino)-acetic acid methyl ester (1196992-44-5) + (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4) → ((R)-2-{(S)-2-[2-((E)-(S)-3-hydroxy-7-tritylsulfanyl-hept-4-enoylamino)-2-methyl-propionylamino]-3-tritylsulfanyl-propionylamino}-3-methyl-butyrylamino)-acetic acid methyl ester (1196992-46-7)

Conditions

Yield

Stage #1: ((R)-2-{(S)-2-[2-(9H-Fluoren-9-ylmethoxycarbonylamino)-2-methyl-propionylamino]-3-tritylsulfanyl-propionylamino}-3-methyl-butyrylamino)-acetic acid methyl ester With diethylamine In acetonitrile at 20℃; for 1.25h; Inert atmosphere; Stage #2: (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane; acetonitrile at 0 - 20℃; Inert atmosphere;

51%

[2-((S)-2-{[1-(9H-fluoren-9-ylmethoxycarbonylamino)-cyclopropanecarbonyl]-amino}-3-tritylsulfanyl-propionylamino)-3-methyl-butyrylamino]-acetic acid methyl ester + (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4) → [2-((S)-2-{[1-((E)-(S)-3-hydroxy-7-tritylsulfanyl-hept-4-enoylamino)-cyclopropanecarbonyl]-amino}-3-tritylsulfanyl-propionylamino)-3-methyl-butyrylamino]-acetic acid methyl ester

Conditions

Yield

Stage #1: [2-((S)-2-{[1-(9H-fluoren-9-ylmethoxycarbonylamino)-cyclopropanecarbonyl]-amino}-3-tritylsulfanyl-propionylamino)-3-methyl-butyrylamino]-acetic acid methyl ester With diethylamine In acetonitrile at 20℃; Inert atmosphere; Stage #2: (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane; acetonitrile at 0 - 20℃; Inert atmosphere;

41%

(E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4) → spiruchostatin A

Conditions	Yield
Multi-step reaction with 4 steps 1: 65 percent / N,N-diisopropylethylamine; benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium PF6(1-) 2: 87 percent / morpholine / Pd(PPh3)4 / methanol 3: 67 percent / MNBA; DMAP / CH2Cl2 4: 100 percent / I2 / methanol; CH2Cl2 View Scheme

(E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4) → (3S,4R)-3-Hydroxy-4-[((E)-(4S,7R,11S)-11-hydroxy-7-methyl-6,9-dioxo-1,2-dithia-5,8-diaza-cyclopentadec-12-ene-4-carbonyl)-amino]-5-methyl-hexanoic acid

Conditions	Yield
Multi-step reaction with 3 steps 1: 65 percent / N,N-diisopropylethylamine; benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium PF6(1-) 2: 87 percent / morpholine / Pd(PPh3)4 / methanol 3: 100 percent / I2 / methanol; CH2Cl2 View Scheme

(E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4) → (2S,6R,9S,12R,13S)-13-Hydroxy-12-isopropyl-6-methyl-2-((E)-4-tritylsulfanyl-but-1-enyl)-9-tritylsulfanylmethyl-1-oxa-5,8,11-triaza-cyclopentadecane-4,7,10,15-tetraone (881845-68-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 65 percent / N,N-diisopropylethylamine; benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium PF6(1-) 2: 87 percent / morpholine / Pd(PPh3)4 / methanol 3: 67 percent / MNBA; DMAP / CH2Cl2 View Scheme

(E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4) → (3S,4R)-3-Hydroxy-4-{(S)-2-[(R)-2-((E)-(S)-3-hydroxy-7-tritylsulfanyl-hept-4-enoylamino)-propionylamino]-3-tritylsulfanyl-propionylamino}-5-methyl-hexanoic acid (878630-45-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 65 percent / N,N-diisopropylethylamine; benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium PF6(1-) 2: 87 percent / morpholine / Pd(PPh3)4 / methanol View Scheme

(E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4) → romidepsin (128517-07-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: 95 percent / (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate, DIEA 2: 98 percent / LiOH 3: EDCl, DMAP, TsOH 4: 84 percent / I2 / methanol; H2O View Scheme

(E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4) → (3S,9S,12R,16S)-6-eth-(Z)-ylidene-3,12-diisopropyl-16-((E)-4-tritylsulfanyl-but-1-enyl)-9-tritylsulfanylmethyl-1-oxa-4,7,10,13-tetraazacyclohexadecane-2,5,8,11,14-pentaone (180973-35-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 95 percent / (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate, DIEA 2: 98 percent / LiOH 3: EDCl, DMAP, TsOH View Scheme

(E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4) → (5E,7S,11R,14S,17E,20S)-17-ethylidene-7-hydroxy-11,20-diisopropyl-9,12,15,18-tetraoxo-1,1,1-triphenyl-14-(tritylthiomethyl)-2-thia-10,13,16,19-tetraazahenicos-5-en-21-oic acid (180973-34-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 95 percent / (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate, DIEA 2: 98 percent / LiOH View Scheme

C51H51ClN3O5PolS + (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (180973-24-4) → C77H75ClN3O7PolS2

Conditions	Yield
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane for 24h;

Upstream product

• 1309766-86-6 ethyl (E)-5-(triphenylmethylthio)-2-pentenoate 
• 150350-28-0 S-trityl 3-mercaptopropionaldehyde 
• 663918-95-4 (3S,4E)-3-hydroxy-1-((4R)-4-isopropyl-2-thioxothiazolidin-3-yl)-7-tritylsulfanyl-hept-4-en-1-one 
• 2409-87-2 methyl (2E)-penta-2,4-dienoate 
• 180973-36-8 (E)-5-Tritylsulfanyl-pent-2-enoic acid methyl ester 
• 180973-37-9 (E)-5-(tritylthio)-2-penten-1-ol 
• 3695-77-0 triphenylmethanethiol 
• 878630-47-8 (E)-(S)-3-hydroxy-1-[(R)-4-isopropyl-5,5-diphenyl-2-oxo-oxazolidin-3-yl]-7-tritylthio-4-hepten-1-one 
• 180973-40-4 (E)-(S)-3-Hydroxy-7-tritylsulfanyl-hept-4-enoic acid benzyl ester 
• 100360-56-3 3-(tritylthio)propan-1-ol 
• 27144-18-9 3-(tritylthio) propanoic acid 
• 76-83-5 trityl chloride 
• 180973-22-2 (2E)-5-[(triphenylmethyl)thio]-2-pentenal 

Downstream Products

• 881845-68-7 (2S,6R,9S,12R,13S)-13-Hydroxy-12-isopropyl-6-methyl-2-((E)-4-tritylsulfanyl-but-1-enyl)-9-tritylsulfanylmethyl-1-oxa-5,8,11-triaza-cyclopentadecane-4,7,10,15-tetraone 
• 878630-45-6 (3S,4R)-3-Hydroxy-4-{(S)-2-[(R)-2-((E)-(S)-3-hydroxy-7-tritylsulfanyl-hept-4-enoylamino)-propionylamino]-3-tritylsulfanyl-propionylamino}-5-methyl-hexanoic acid 
• 1043577-31-6 (S,E)-2-(trimethylsilyl)ethyl 3-(((S)-2-amino-3-methylbutanoyl)oxy)-7-(tritylthio)hept-4-enoate 
• 1309766-85-5 allyl (3S,4R,5S)-4-[(S)-2-{(R)-2-[(E)-(S)-3-hydroxy-7-(tritylthio)-4-heptenoylamino]propionylamino}-3-(tritylthio)propionylamino]-3-hydroxy-5-methylheptanoate 
• 1309766-89-9 (2S,6R,9S,12R,13S)-12-((S)-sec-butyl)-13-hydroxy-6-methyl-2-[(E)-4-tritylthio-1-butenyl]-9-tritylthiomethyl-1-oxa-5,8,11-triaza-cyclopentadecane-4,7,10,15-tetraone 
• 1089192-66-4 (S,E)-2-(trimethylsilyl)ethyl 3-(((S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl) amino)-3-methylbutanoyl)oxy)-7-(tritylthio)hept-4-enoate 
• 1137735-74-0 (S,E)-2-(trimethylsilyl)ethyl 3-(((S)-2-amino-3-methylbutanoyl)oxy)-7-(tritylthio)hept-4-enoate 
• 1196992-58-1 [(1-{(S)-2-[2-((E)-(S)-3-hydroxy-7-tritylsulfanyl-hept-4-enoylamino)-acetylamino]-3-tritylsulfanyl-propionylamino}-cyclopropanecarbonyl)-amino]-acetic acid methyl ester 
• 1196992-72-9 [(1-{(S)-2-[(R)-3-(3-chloro-phenyl)-2-((E)-(S)-3-hydroxy-7-tritylsulfanyl-hept-4-enoylamino)-propionylamino]-3-tritylsulfanyl-propionylamino}-cyclopropanecarbonyl)-amino]-acetic acid methyl ester 
• 1196992-65-0 C₆₃H₆₃N₅O₇S₂ 
• 1196992-37-6 (R)-4-((E)-(S)-3-hydroxy-7-tritylsulfanyl-hept-4-enoylamino)-4-{(S)-1-[1-(methoxycarbonylmethyl-carbamoyl)-cyclobutylcarbamoyl]-2-tritylsulfanyl-ethylcarbamoyl}-butyric acid tert-butyl ester 
• 1196992-18-3 (R)-4-((E)-(S)-3-hydroxy-7-tritylsulfanyl-hept-4-enoylamino)-4-{(S)-1-[1-(methoxycarbonylmethyl-carbamoyl)-cyclopropylcarbamoyl]-2-tritylsulfanyl-ethylcarbamoyl}-butyric acid tert-butyl ester 
• 1196992-07-0 (R)-4-((E)-(S)-3-hydroxy-7-tritylsulfanyl-hept-4-enoylamino)-4-{(S)-1-[1-(methoxycarbonylmethyl-carbamoyl)-1-methyl-ethylcarbamoyl]-2-tritylsulfanyl-ethylcarbamoyl}-butyric acid tert-butyl ester 
• 1196991-93-1 (R)-4-{(S)-1-[1-(1-hydroxy-2-methoxycarbonyl-ethyl)-cyclopropylcarbamoyl]-2-tritylsulfanyl-ethylcarbamoyl}-4-((E)-(S)-3-hydroxy-7-tritylsulfanyl-hept-4-enoylamino)-butyric acid tert-butyl ester 

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