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
• Article Data: 13

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

PGX 9 is a useful intermediate in the chemoenzymatic synthesis of Latanoprost and Bimatoprost, that are prostaglandin analogs widely used for glaucoma treatment.

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

• 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 
• 944269-28-7 benzyl(1R,2R,3R)-3-hydroxy-2-[5-phenyl-(3S)-hydroxy-(1E)-pentenyl]-5-oxo-cyclopentane-acetate 

Downstream Products

• 69610-63-5 (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 
• 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 
• 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 
• 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 
• 38344-08-0 (5Z)-bimatoprost acid 
• 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 
• 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 
• 155206-00-1 bimatoprost 
• 41639-83-2 latanoprost acid 

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.

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.

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.