41639-74-1

Basic information

• Product Name: HYDRIDE-L
• Synonyms: HYDRIDE-L;(+)-(3aR,4R,5r,6aS)-Hexahydro-5-hydroxy-4-[(1E,3R)-3-hydroxy-5-phenyl-1-pentenyl]-2H-cyclopenta[b]furan-2-one;BP-2 (LT-EDI);BP-2 (LT-EDI)(Bimaprost、Latanprost);(3aR,4R,5R,6aS)-5-Hydroxy-4-((S,E)-3-hydroxy-5-phenylpent-1-en-1-yl)hexahydro-2H-cyclopenta[b]furan-2-one;2H-Cyclopenta[b]furan-2-one,hexahydro-5-hydroxy-4-[(1E,3S)-3-hydroxy-5-phenyl-1-penten-1-yl]-,(3aR,4R,5R,6aS)-;(3aR,4R,5R,6aS)-Hexahydro-5-hydroxy-4-[(1E,3S)-3-hydroxy-5-phenyl-1-penten-1-yl]-2H-cyclopenta[b]furan-2-one;Lactondiol B
• CAS NO: 41639-74-1
• Molecular Formula: C₁₈H₂₂O₄
• Molecular Weight: 302.36
• Mol File: 41639-74-1.mol

Chemical Properties

• Boiling Point: 509.18 °C at 760 mmHg
• Flash Point: 185.604 °C
• Appearance: /
• Density: 1.287 g/cm³
• Refractive Index: 1.64
• Storage Temp.: 2-8°C
• CAS DataBase Reference: HYDRIDE-L(CAS DataBase Reference)
• NIST Chemistry Reference: HYDRIDE-L(41639-74-1)
• EPA Substance Registry System: HYDRIDE-L(41639-74-1)

Safety Data

• Hazardous Substances Data: 41639-74-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
HYDRIDE-L is used as an intermediate in the chemoenzymatic synthesis of Latanoprost and Bimatoprost, which are prostaglandin analogs. These analogs are widely used for the treatment of glaucoma, a group of eye conditions that damage the optic nerve, leading to vision loss.
Used in Chemical Synthesis:
HYDRIDE-L is also used as a key component in the synthesis of various chemicals and compounds. Its unique properties make it an essential building block in the creation of new and innovative products.
Used in Research and Development:
Due to its diverse applications, HYDRIDE-L is also utilized in research and development for the discovery and creation of new compounds and materials. Its versatility allows researchers to explore its potential in various fields, leading to new breakthroughs and advancements.

InChI:InChI=1/C18H22O4/c19-13(7-6-12-4-2-1-3-5-12)8-9-14-15-10-18(21)22-17(15)11-16(14)20/h1-5,8-9,13-17,19-20H,6-7,10-11H2/b9-8+/t13-,14+,15+,16+,17-/m0/s1

Synthetic route

(3aR,4R,5R,6aS)-5-hydroxy-4-((E)-3-oxo-5-phenylpent-1-en-1-yl)hexahydro-2H-cyclopenta[b]furan-2-one → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions	Yield
Stage #1: (3aR,4R,5R,6aS)-5-hydroxy-4-((E)-3-oxo-5-phenylpent-1-en-1-yl)hexahydro-2H-cyclopenta[b]furan-2-one With chlorobis(2,6,6-trimethylbicyclo[3.1.1]heptan-3-yl)borane In tetrahydrofuran at -40℃; for 12h; Stage #2: With hydrogenchloride In water at 20℃; for 0.5h; Reagent/catalyst; Temperature;	88%
With C20H35B In tetrahydrofuran; hexane at -40℃; for 12h;	76%

(3aR,4R,5R,6aS)-4-[(1E,3S)-3-hydroxy-5-phenylpent-1-en-1-yl]-2-oxo-hexahydro-2H-cyclopenta[b]furan-5-yl benzoate (55444-68-3) → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions	Yield
With potassium carbonate In methanol at 25℃; for 2h;	83%
With methanol; potassium carbonate deprotection;

(1S,5R,6R,7R)-6-<(3R)-3-hydroxy-5-phenyl-1-pentenyl>-7-<(4-phenylbenzoyl)oxy>-2-oxabicyclo<3.3.0>octan-3-one (41639-73-0) → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions	Yield
With methanol; potassium carbonate	80%
With potassium carbonate In tetrahydrofuran; methanol for 2.5h;
Stage #1: (1S,5R,6R,7R)-6-<(3R)-3-hydroxy-5-phenyl-1-pentenyl>-7-<(4-phenylbenzoyl)oxy>-2-oxabicyclo<3.3.0>octan-3-one With methanol; potassium carbonate at 20 - 30℃; Stage #2: With hydrogenchloride In water; ethyl acetate at 20 - 30℃; for 0.5h;

benzyl(1R,2R,3R)-3-hydroxy-2-[5-phenyl-(3S)-hydroxy-(1E)-pentenyl]-5-oxo-cyclopentane-acetate (944269-28-7) → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions	Yield
With L-Selectride In tetrahydrofuran at -70℃; for 2h; Product distribution / selectivity;	78%

benzyl (1R,2R,3R)-3-hydroxy-2-[5-phenyl-(3S)-3-hydroxy-1-pentenyl]-5-oxo-cyclopentaneacetate → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions	Yield
Stage #1: benzyl (1R,2R,3R)-3-hydroxy-2-[5-phenyl-(3S)-3-hydroxy-1-pentenyl]-5-oxo-cyclopentaneacetate With L-Selectride In tetrahydrofuran at -70℃; for 2h; Cooling with methanol-dry ice; Stage #2: With water; ammonium chloride In tetrahydrofuran Product distribution / selectivity;	78%

(1R,2'S,5'R)-methyl(1R,2R,3R)-3-hydroxy-2-[5-phenyl-(3S)-hydroxy-(1E)-pentenyl]-5-oxo-acetate → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions	Yield
With L-Selectride In tetrahydrofuran at -70℃; for 2h; Product distribution / selectivity;	77%

(1'R,2'S,5'R)-menthyl (1R,2R,3R)-3-hydroxy-2-[5-phenyl-(3S)-3-hydroxy-1-pentenyl]-5-oxo-cyclopentaneacetate → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions	Yield
Stage #1: (1'R,2'S,5'R)-menthyl (1R,2R,3R)-3-hydroxy-2-[5-phenyl-(3S)-3-hydroxy-1-pentenyl]-5-oxo-cyclopentaneacetate With L-Selectride In tetrahydrofuran at -70℃; for 2h; Cooling with methanol-dry ice; Stage #2: With water; ammonium chloride In tetrahydrofuran Product distribution / selectivity;	77%

C38H33NO8 → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions	Yield
With potassium carbonate In methanol; dichloromethane at 25 - 30℃; Inert atmosphere;	77%

ethyl (1R,2R,3R) 3-hydroxy-2-[5-phenyl-(3S)-hydroxy-(1E)-pentenyl]-5-oxo-cyclopentane acetate → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions	Yield
With L-Selectride In tetrahydrofuran at -70℃; for 2h; Product distribution / selectivity;	75%

ethyl (1R,2R,3R)-3-hydroxy-2-[5-phenyl-(3S)-3-hydroxy-1-pentenyl]-5-oxo-cyclopentaneacetate → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions	Yield
Stage #1: ethyl (1R,2R,3R)-3-hydroxy-2-[5-phenyl-(3S)-3-hydroxy-1-pentenyl]-5-oxo-cyclopentaneacetate With L-Selectride In tetrahydrofuran at -70℃; for 2h; Cooling with methanol-dry ice; Stage #2: With water; ammonium chloride In tetrahydrofuran Product distribution / selectivity;	75%

2-naphthyl (1R,2R,3R)-3-hydroxy-2-[(E)-5-phenyl-(3S)-hydroxy-1-pentenyl]-5-oxo-cyclopentane acetate → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions	Yield
With L-Selectride In tetrahydrofuran at -70℃; for 2h; Product distribution / selectivity;	68%

2-naphthyl (1R,2R,3R)-3-hydroxy-2-[5-phenyl-(3S)-3-hydroxy-1-pentenyl]-5-oxo-cyclopentaneacetate → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions	Yield
Stage #1: 2-naphthyl (1R,2R,3R)-3-hydroxy-2-[5-phenyl-(3S)-3-hydroxy-1-pentenyl]-5-oxo-cyclopentaneacetate With L-Selectride In tetrahydrofuran at -70℃; for 2h; Cooling with methanol-dry ice; Stage #2: With water; ammonium chloride In tetrahydrofuran Product distribution / selectivity;	68%

(E)-3-phenylacrylic acid (140-10-3) → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: H2 / 5 percent Pd/C / ethyl acetate 2.1: MeOH 3.1: N-BuLi / tetrahydrofuran / 0 °C 3.2: tetrahydrofuran 4.1: NaHMDS / 1,2-dimethoxy-ethane 4.2: 1,2-dimethoxy-ethane 5.1: (S)-BINAL-H; LiAlH4 / tetrahydrofuran 6.1: K2CO3; MeOH View Scheme

3-phenylpropanoic acid methyl ester (103-25-3) → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: N-BuLi / tetrahydrofuran / 0 °C 1.2: tetrahydrofuran 2.1: NaHMDS / 1,2-dimethoxy-ethane 2.2: 1,2-dimethoxy-ethane 3.1: (S)-BINAL-H; LiAlH4 / tetrahydrofuran 4.1: K2CO3; MeOH View Scheme

dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: NaHMDS / 1,2-dimethoxy-ethane 1.2: 1,2-dimethoxy-ethane 2.1: (S)-BINAL-H; LiAlH4 / tetrahydrofuran 3.1: K2CO3; MeOH View Scheme
Multi-step reaction with 3 steps 1: 1.) NaH / 1.) THF, 90 min, 2.) THF, 30 min 2: lithium triethylborohydride / tetrahydrofuran / 0.5 h 3: potassium carbonate / methanol; tetrahydrofuran / 2.5 h View Scheme

(3aR,4R,5R,6aS)-2-oxo-4-((1E)-3-oxo-5-phenylpent-1-en-1-yl)-hexahydro-2H-cyclopenta[b]furan-5-yl benzoate (55076-60-3) → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: (S)-BINAL-H; LiAlH4 / tetrahydrofuran 2: K2CO3; MeOH View Scheme
Multi-step reaction with 2 steps 1: (-)-diisopinocamphenylborane chloride / dichloromethane / 26 h / -25 - 30 °C 2: potassium carbonate / methanol / 2 h / 25 °C View Scheme

3-Phenylpropionic acid (501-52-0) → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: MeOH 2.1: N-BuLi / tetrahydrofuran / 0 °C 2.2: tetrahydrofuran 3.1: NaHMDS / 1,2-dimethoxy-ethane 3.2: 1,2-dimethoxy-ethane 4.1: (S)-BINAL-H; LiAlH4 / tetrahydrofuran 5.1: K2CO3; MeOH View Scheme

(1S,5R,6R,7R)-6-(3-oxo-5-phenyl-1E-pentenyl)-7-<(4-phenylbenzoyl)oxy>-2-oxabicyclo<3.3.0>octan-3-one (41639-72-9) → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: lithium triethylborohydride / tetrahydrofuran / 0.5 h 2: potassium carbonate / methanol; tetrahydrofuran / 2.5 h View Scheme

(3aR,4R,5R,6aS)-4-formyl-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl biphenyl-4-carboxylate (38754-71-1) → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) NaH / 1.) THF, 90 min, 2.) THF, 30 min 2: lithium triethylborohydride / tetrahydrofuran / 0.5 h 3: potassium carbonate / methanol; tetrahydrofuran / 2.5 h View Scheme

benzoic acid (3aR,4R,5R,6aS)-4-((E)-3-hydroxy-5-phenyl-pent-1-enyl)-2-oxo-hexahydro-cyclopenta[b]furan-5-yl ester → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions	Yield
Stage #1: benzoic acid (3aR,4R,5R,6aS)-4-((E)-3-hydroxy-5-phenyl-pent-1-enyl)-2-oxo-hexahydro-cyclopenta[b]furan-5-yl ester With methanol; sodium methylate for 2h; Stage #2: With hydrogenchloride In methanol; water at 0 - 5℃; pH=6.5; Product distribution / selectivity;

(3aR,4R,6aS)-2-oxo-4-((E)-3-oxo-5-phenylpent-1-enyl)hexahydro-2H-cyclopenta[b]furan-5-yl biphenyl-4-carboxylate → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / toluene; tetrahydrofuran / 0.5 h / 25 °C / Inert atmosphere 1.2: -20 - 0 °C / Inert atmosphere 1.3: pH 3 2.1: potassium carbonate; methanol / 2 h / 25 °C View Scheme

(3aR,4R,6aS)-4-((S,E)-3-hydroxy-5-phenylpent-1-enyl)-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl biphenyl-4-carboxylate → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions	Yield
With methanol; potassium carbonate at 25℃; for 2h;

(3aR,4R,6aS)-4-formyl-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl biphenyl-4-carboxylate → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium hydride / dichloromethane / 1 h / 0 °C 1.2: 0 - 5 °C 2.1: (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / toluene; tetrahydrofuran / 0.5 h / 25 °C / Inert atmosphere 2.2: -20 - 0 °C / Inert atmosphere 2.3: pH 3 3.1: potassium carbonate; methanol / 2 h / 25 °C View Scheme

C21H20O5 → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 1 h / -70 °C / Inert atmosphere 1.2: 1 h / Inert atmosphere 2.1: sodium hydride / dichloromethane / 1 h / 0 °C 2.2: 0 - 5 °C 3.1: (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / toluene; tetrahydrofuran / 0.5 h / 25 °C / Inert atmosphere 3.2: -20 - 0 °C / Inert atmosphere 3.3: pH 3 4.1: potassium carbonate; methanol / 2 h / 25 °C View Scheme

4-Phenyl-2-butanone (2550-26-7) → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions	Yield
Multi-step reaction with 5 steps 1: acetic acid; bromine / methanol / 2 h / -5 - 20 °C 2: acetonitrile / 1 h / 80 °C 3: lithium chloride; triethylamine / tetrahydrofuran / 2 h / -4 - 20 °C 4: (-)-diisopinocamphenylborane chloride / dichloromethane / 26 h / -25 - 30 °C 5: potassium carbonate / methanol / 2 h / 25 °C View Scheme

diethyl (2-oxo-4-phenylbutyl)phosphonate (40601-45-4) → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: lithium chloride; triethylamine / tetrahydrofuran / 2 h / -4 - 20 °C 2: (-)-diisopinocamphenylborane chloride / dichloromethane / 26 h / -25 - 30 °C 3: potassium carbonate / methanol / 2 h / 25 °C View Scheme

1-bromo-4-phenylbutan-2-one (31984-10-8) → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: acetonitrile / 1 h / 80 °C 2: lithium chloride; triethylamine / tetrahydrofuran / 2 h / -4 - 20 °C 3: (-)-diisopinocamphenylborane chloride / dichloromethane / 26 h / -25 - 30 °C 4: potassium carbonate / methanol / 2 h / 25 °C View Scheme

(+/-)-7,7-dichlorobicyclo[3.2.0]hept-2-en-6-one (5307-99-3) → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: (S)-6,6'-bis(2,4,6-triisopropylphenyl)-1,1'-spirobiindane-7,7'-diyl hydrogenphosphate; dihydrogen peroxide / chloroform; water / -15 °C / Schlenk technique 2.1: ammonium chloride; zinc / methanol / 3 h / 70 °C 3.1: formic acid; sulfuric acid / 24 h / 80 °C 3.2: 2 h / 0 - 20 °C 4.1: [bis(acetoxy)iodo]benzene; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical / dichloromethane; N,N-dimethyl acetamide / 6 h / 20 °C 5.1: sodium hydride / tetrahydrofuran / 1 h / 0 °C / Inert atmosphere 5.2: 6 h / 0 - 20 °C / Inert atmosphere 6.1: C20H35B / tetrahydrofuran; hexane / 12 h / -40 °C View Scheme
Multi-step reaction with 6 steps 1.1: (S)-6,6'-bis(2,4,6-triisopropylphenyl)-1,1'-spirobiindane-7,7'-diyl hydrogenphosphate; dihydrogen peroxide / chloroform; water / 48 h / 0 °C / Schlenk technique 2.1: ammonium chloride; zinc / methanol / 3 h / 70 °C 3.1: formic acid; sulfuric acid / 24 h / 80 °C 3.2: 2 h / 0 - 20 °C 4.1: [bis(acetoxy)iodo]benzene; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical / dichloromethane; N,N-dimethyl acetamide / 6 h / 20 °C 5.1: sodium hydride / tetrahydrofuran / 1 h / 0 °C / Inert atmosphere 5.2: 6 h / 0 - 20 °C / Inert atmosphere 6.1: C20H35B / tetrahydrofuran; hexane / 12 h / -40 °C View Scheme

(-)-(1S,5R)-2-oxabicyclo[3.3.0]oct-6-en-3-one (26054-46-6) → (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: formic acid; sulfuric acid / 24 h / 80 °C 1.2: 2 h / 0 - 20 °C 2.1: [bis(acetoxy)iodo]benzene; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical / dichloromethane; N,N-dimethyl acetamide / 6 h / 20 °C 3.1: sodium hydride / tetrahydrofuran / 1 h / 0 °C / Inert atmosphere 3.2: 6 h / 0 - 20 °C / Inert atmosphere 4.1: C20H35B / tetrahydrofuran; hexane / 12 h / -40 °C View Scheme

(3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1) → (1S,5R,6R,7R)-6-<(3S)-3-hydroxy-5-phenyl-1-pentyl>-7(R)-hydroxy-2-oxabicyclo<3.3.0>octan-3-one (145667-75-0)

Conditions	Yield
With 5%-palladium/activated carbon; hydrogen; sodium hydroxide In ethanol at 20℃; under 760.051 Torr; for 5h;	100%
With palladium 10% on activated carbon; hydrogen; sodium hydroxide In ethanol at 20℃; under 3000.3 Torr;	85%
With sodium hydroxide; hydrogen; 5%-palladium/activated carbon In ethyl acetate Product distribution / selectivity;	78%

3,4-dihydro-2H-pyran (110-87-2) + (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1) → (3aR,4R,5R,6aS)-hexahydro-4-((3S,E)-5-phenyl-3-(tetrahydro-2H-pyran-2-yloxy)pent-1-enyl)-5-(tetrahydro-2H-pyran-2-yloxy)cyclopenta[b]furan-2-one (69610-63-5)

Conditions	Yield
With toluene-4-sulfonic acid In dichloromethane at 20℃; for 2.5h;	89.9%
With toluene-4-sulfonic acid In dichloromethane at 20℃; for 2.5h;	89.9%
With toluene-4-sulfonic acid In dichloromethane for 0.5h;
With toluene-4-sulfonic acid In dichloromethane Etherification;

(3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1) → (3aR,4R,5R,6aS)-4-[(1E,3S)-3-hydroxy-5-phenylpent-1-en-1-yl]-hexahydro-2H-cyclopenta[b]furan-2,5-diol (856240-62-5)

Conditions	Yield
With diisobutylaluminium hydride In tetrahydrofuran at -70℃; for 2h;	81%
With diisobutylaluminium hydride
With diisobutylaluminium hydride In dichloromethane at -78℃; for 2h;
Stage #1: (3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one With diisobutylaluminium hydride In dichloromethane at -78℃; for 2h; Stage #2: With ammonium chloride at 20℃; for 0.25h; Reagent/catalyst; Temperature;

(3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1) → (Z)-7-[(1R,2R,3R,5S)-3,5-Dihydroxy-2-((E)-(S)-3-hydroxy-5-phenyl-pent-1-enyl)-cyclopentyl]-hept-5-enoic acid

Conditions	Yield
Multi-step reaction with 4 steps 1: p-TSA / CH2Cl2 2: DIBAL-H / -78 °C 3: NaHMDS 4: aq. AcOH / tetrahydrofuran View Scheme

(3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1) → 7-[(1R,2R,3R,5S)-3,5-Dihydroxy-2-((R)-3-hydroxy-5-phenyl-pentyl)-cyclopentyl]-heptanoic acid

Conditions	Yield
Multi-step reaction with 5 steps 1: p-TSA / CH2Cl2 2: DIBAL-H / -78 °C 3: NaHMDS 4: aq. AcOH / tetrahydrofuran 5: H2 / 5 percent Pd/C / ethyl acetate View Scheme

(3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1) → [(1R,2R,3R,5S)-5-Hydroxy-2-[(E)-(S)-5-phenyl-3-(tetrahydro-pyran-2-yloxy)-pent-1-enyl]-3-(tetrahydro-pyran-2-yloxy)-cyclopentyl]-acetaldehyde

Conditions	Yield
Multi-step reaction with 2 steps 1: p-TSA / CH2Cl2 2: DIBAL-H / -78 °C View Scheme

(3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1) → 7-((1R,2R,3R,5S)-5-hydroxy-2-((3S,E)-5-phenyl-3-(tetrahydro-2H-pyran-2-yloxy)pent-1-enyl)-3-(tetrahydro-2H-pyran-2-yloxy)cyclopentyl)hept-5-enoic acid

Conditions	Yield
Multi-step reaction with 3 steps 1: p-TSA / CH2Cl2 2: DIBAL-H / -78 °C 3: NaHMDS View Scheme
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 2.5 h / 20 °C 2.1: diisobutylaluminium hydride / toluene; hexane / -70 °C 3.1: potassium tert-butylate / tetrahydrofuran / 0.5 h / -20 °C 3.2: 16 h / -20 °C View Scheme
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 2.5 h / 20 °C 2.1: diisobutylaluminium hydride / hexane; toluene / -70 °C 3.1: potassium tert-butylate / tetrahydrofuran / 0.5 h / -20 °C 3.2: 16 h / -20 °C View Scheme

(3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1) → N-(methanesulfonyl)-17-phenyl-ω-trinor-PGE2-carboxamide (69590-43-8)

Conditions	Yield
Multi-step reaction with 5 steps 1: p-toluenesulfonic acid / CH2Cl2 / 0.5 h 2: diisobutylaluminum hydride / toluene; hexane / 0.33 h 3: 1.) sodium methylsulfinylcarbanide / 1.) Me2SO, 2.) Me2SO, 2 h 4: Jones reagent / acetone / 0.08 h / -20 °C 5: 65percent aq. acetic acid / 14 h / Ambient temperature View Scheme

(3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1) → (3aR,4R,5R,6aS)-hexahydro-4-((3S,E)-5-phenyl-3-(tetrahydro-2H-pyran-2-yloxy)pent-1-enyl)-5-(tetrahydro-2H-pyran-2-yloxy)-2H-cyclopenta[b]furan-2-ol (856453-32-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: p-toluenesulfonic acid / CH2Cl2 / 0.5 h 2: diisobutylaluminum hydride / toluene; hexane / 0.33 h View Scheme
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / dichloromethane / 2.5 h / 20 °C 2: diisobutylaluminium hydride / toluene; hexane / -70 °C View Scheme
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / dichloromethane / 2.5 h / 20 °C 2: diisobutylaluminium hydride / hexane; toluene / -70 °C View Scheme

(3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1) → N-{(Z)-7-[(1R,2R,3R,5S)-5-Hydroxy-2-[(E)-(S)-5-phenyl-3-(tetrahydro-pyran-2-yloxy)-pent-1-enyl]-3-(tetrahydro-pyran-2-yloxy)-cyclopentyl]-hept-5-enoyl}-methanesulfonamide (69590-40-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: p-toluenesulfonic acid / CH2Cl2 / 0.5 h 2: diisobutylaluminum hydride / toluene; hexane / 0.33 h 3: 1.) sodium methylsulfinylcarbanide / 1.) Me2SO, 2.) Me2SO, 2 h View Scheme

(3aR,4R,5R,6aS)-hexahydro-5-hydroxy-4-[(1E,3S)-5-phenyl-3-hydroxy-(1E)-pentenyl]-2H-cyclopentane [β] furan-2-one (41639-74-1) → N-{(Z)-7-[(1R,2R,3R)-5-Oxo-2-[(E)-(S)-5-phenyl-3-(tetrahydro-pyran-2-yloxy)-pent-1-enyl]-3-(tetrahydro-pyran-2-yloxy)-cyclopentyl]-hept-5-enoyl}-methanesulfonamide (69590-42-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: p-toluenesulfonic acid / CH2Cl2 / 0.5 h 2: diisobutylaluminum hydride / toluene; hexane / 0.33 h 3: 1.) sodium methylsulfinylcarbanide / 1.) Me2SO, 2.) Me2SO, 2 h 4: Jones reagent / acetone / 0.08 h / -20 °C View Scheme

Upstream product

• 103-25-3 3-phenylpropanoic acid methyl ester 
• 933789-26-5 (3aR,4R,5R,6aS)-5-hydroxy-4-((E)-3-oxo-5-phenylpent-1-en-1-yl)hexahydro-2H-cyclopenta[b]furan-2-one 
• 62961-72-2 Corey aldehyde 
• 87422-39-7 (3aR,6aS)-3,3-dichloro-3,3a,6,6a-tetrahydro-2H-cyclopenta[b]furan-2-one 
• 32233-40-2 (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one 
• 542-92-7 cyclopenta-1,3-diene 
• 26054-46-6 (-)-(1S,5R)-2-oxabicyclo[3.3.0]oct-6-en-3-one 
• 5307-99-3 (+/-)-7,7-dichlorobicyclo[3.2.0]hept-2-en-6-one 
• 31984-10-8 1-bromo-4-phenylbutan-2-one 
• 40601-45-4 diethyl (2-oxo-4-phenylbutyl)phosphonate 
• 2550-26-7 4-Phenyl-2-butanone 

Downstream Products

• 1300092-81-2 C₂₆H₃₈O₈ 
• 1300092-82-3 (3aR,4R,5R,6aS)-5-((2-methoxyethoxy)methoxy)-4-((R)-3-((2-methoxyethoxy)methoxy)-5-phenylpentyl)hexahydro-2H-cyclopenta[b]furan-2-one 
• 1300092-83-4 (3aR,4R,5R,6aS)-5-((2-methoxyethoxy)methoxy)-4-((R)-3-((2-methoxyethoxy)methoxy)-5-phenylpentyl)hexahydro-2H-cyclopenta[b]furan-2-ol 
• 1300092-85-6 (Z)-7-((1R,2R,3R,5S)-5-hydroxy-3-((2-methoxyethoxy)methoxy)-2-((R)-3-((2-methoxyethoxy)methoxy)-5-phenylpentyl)cyclopentyl)hept-5-enoic acid 
• 1300092-87-8 (Z)-isopropyl 7-((1R,2R,3R,5S)-5-hydroxy-3-((2-methoxyethoxy)methoxy)-2-((R)-3-((2-methoxyethoxy)methoxy)-5-phenylpentyl)cyclopentyl)hept-5-enoate 
• 130209-82-4 latanoprost 
• 41639-83-2 latanoprost acid 
• 155206-00-1 bimatoprost 
• 856240-52-3 (5Z)-N-ethyl-7-((1R,2R,3R,5S)-5-hydroxy-2-((3S,E)-5-phenyl-3-(tetrahydro-2H-pyran-2-yloxy)pent-1-enyl)-3-(tetrahydro-2H-pyran-2-yloxy)cyclopentyl)hept-5-enamide 
• 38315-47-8 (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-((S)-(E)-3-hydroxy-5-phenylpent-1-enyl)-cyclopentyl]hept-5-enoic acid methyl ester 
• 38344-08-0 (5Z)-bimatoprost acid 
• 1240483-15-1 (3aR,4R,5R,6aS)-5-((tert-butyldimethylsilyl)oxy)-4-((S,E)-3-((tert-butyldimethylsilyl)oxy)-5-phenylpent-1-en-1-yl)hexahydro-2H-cyclopenta[b]furan-2-one 
• 145667-75-0 (1S,5R,6R,7R)-6-<(3S)-3-hydroxy-5-phenyl-1-pentyl>-7(R)-hydroxy-2-oxabicyclo<3.3.0>octan-3-one 
• 856240-62-5 (3aR,4R,5R,6aS)-hexahydro-4-[(1E,3S)-3-hydroxy-5-phenyl-1-penten-1-yl]-2H-cyclopenta[b]furan-2,5-diol 

Relevant articles and documents

Preparation method of bemeprost

The invention discloses a preparation method of bemeprost, which comprises the following steps: (1) in a first solvent, carrying out oxidation reaction on a compound 1 in an oxidation system to generate a compound 2; (2) in a second solvent, under the action of alkali, mixing the compound 2 with a compound 7 for reaction to generate a compound 3; (3) carrying out reduction reaction on the compound3 in a third solvent under the action of a first reducing agent to generate a compound 4; (4) in a fourth solvent, carrying out reduction reaction on the compound 4 under the action of a second reducing agent to generate a compound 5; and (5) in a fifth solvent, under the action of alkali, carrying out the following reaction on the compound 5 and the compound 8 to generate bemeprost of a compound6. According to the preparation method disclosed by the invention, the operation steps are remarkably simplified, the reaction conditions are mild, and the operation is simple and convenient; raw materials are cheap and easy to obtain, and cost is reduced; the product yield is high, and the method is suitable for industrial production.

An improved synthesis of latanoprost involving effective control on 15(S) diastereomer

An improved process for the synthesis of latanoprost having excellent optical purity (de 99.9%, [α]D20 = +35.37° (c = 0.90, acetonitrile)) without use of preparative HPLC is described. This process involves effective purification of hydroxyl intermediate (5A) through solvent crystallization followed by inhibition of inversion of the chiral center at C-15 position. This was possible due to judicious use of diol intermediate (6) for double bond reduction prior to hydroxyl protection.

Access to a Key Building Block for the Prostaglandin Family via Stereocontrolled Organocatalytic Baeyer–Villiger Oxidation

A new protocol for the construction of a crucial bicyclic lactone of prostaglandins using a stereocontrolled organocatalytic Baeyer–Villiger (B-V) oxidation was developed. The key B-V oxidation of a racemic cyclobutanone derivative with aqueous hydrogen peroxide has enabled an early-stage construction of a bicyclic lactone skeleton in high enantiomeric excess (up to 95 %). The generated bicyclic lactone is fully primed with two desired stereocenters and enabled the synthesis of the entire family of prostaglandins according to Corey′s route. Furthermore, the reactivity and enantioselectivity of B-V oxidation of racemic bicyclic cyclobutanones were evaluated and 90–99 % ee was obtained, representing one of the most efficient routes to chiral lactones. This study further facilitates the synthesis of prostaglandins and chiral lactone-containing natural products to promote drug discovery.

Novel method for preparing Prostaglandin derivatives

Provided is a novel method for preparing prostaglandin derivatives. The method is suitable for mass production by effectively manufacturing prostaglandin derivatives with high yield. The method comprises the following steps: (S-1) adding a first reducing agent to a prostaglandin intermediate compound represented by chemical formula II and manufacturing a compound represented by chemical formula III; (S-2) manufacturing a compound represented by chemical formula IV from the compound represented by chemical formula III in the presence of a base; (S-3) adding a second reducing agent to the compound represented by chemical formula IV and manufacturing a compound represented by chemical formula V; and (S-4) performing Wittig reaction of the compound represented by chemical formula V and a compound represented by chemical formula VI, and manufacturing a compound represented by chemical formula I.COPYRIGHT KIPO 2017

PROCESSES AND INTERMEDIATES FOR THE PREPARATIONS OF PROSTAGLANDINS

A method for preparing cyclopentanones or lactones is provided to be useful for preparation of prostagladins, to remove problems such as the long synthesis route and the removal of undesired isomers, and thus achieves a simple and economical synthesis route. The method for preparing a compound of the following formula II having an enantiomer purity higher than 95% e.e.(enantiomeric excess) comprises the steps of: reacting a compound of the following formula IV having an optical purity higher than 90% e.e. with cuprate; and optionally performing a de-protection reaction of the obtained compound to convert P1, P2, or both P1 and P2 into H. In the formulae, Z does not take part in coupling and de-protection reactions and is an optional group acting as a leaving group in reduction/lactonization reactions, R2 is a single bond, C1-4 alkylene or -CH2O- group, R3 is a C1-7-alkyl or aryl or aralkyl unsubstituted or substituted by C1-4 alkyl, halogen or trihalomethyl, X1 and X2 are independently hydrogen or P1 and P2, respectively, wherein P1 and P2 are protective groups for hydroxyl groups which are identical to or different from each other.

A NOVEL PROCESS FOR THE PREPARATION OF PROSTAGLANDINS AND INTERMEDIATES THEREOF

This invention relates to novel process for the preparation of prostaglandin compounds having formula (K), wherein R is selected from the group consisting of C1-C7 alkyl; C7-C17 aralkyl wherein the aryl group is unsubstituted or substituted with one to three substituents selected from the group consisting of C1-C6 alkyl, halo and CF3; and (CH2)nOR2 wherein n is from 1 to 3 and R2 represents a C6-C10 aryl group which is unsubstituted or substituted with one to three substituents selected from the group consisting of C1-C6 alkyl, halo and CF3; and R1 is selected from OR3 and NHR3 wherein R3 is C1-C6 alkyl, H; and dashed lines represents a double bond or a single bond, is disclosed. Novel intermediates are also disclosed.

IMPROVED PROCESS FOR THE PREPARATION OF PROSTAGLANDINS AND ANALOGUES THEREOF

The present invention relates to an improved process for the preparation of prostaglandin and prostaglandin analogues, particularly PGF2α derivatives.

Improved Process for the Production of Prostaglandins and Prostaglandin Analogs

The present invention relates to an improved process for the production of prostaglandins and prostaglandin analogs. In particular, this invention relates to the production of prostaglandins of the PGF2α-series, including latanoprost, travoprost, and bimatoprost, which are active pharmaceutical ingredients used for the reduction of elevated intraocular pressure in patients with glaucoma and ocular hypertension.

Processes and intermediates for the preparations of prostaglandins

The present invention provides novel processes for the preparation of a cyclopentanone of Formula II and a lactone of Formula I, which are useful in the production of prostaglandins: wherein Z, R2, R3, X1, X2, and are as defined in the specification. The invention also provides novel enantiomerically enriched compounds.

Processes and intermediates for the preparations of prostaglandins

The present invention provides novel processes for the preparation of a cyclopentanone of Formula II and a lactone of Formula I, which are useful in the production of prostaglandins: wherein Z, R2, R3, X1, X2, and ------------ are as defined in the specification. The invention also provides novel enantiomerically enriched compounds.