130209-76-6

Usage

InChI:InChI=1/C26H38O5/c1-19(2)31-26(30)13-9-4-3-8-12-22-23(25(29)18-24(22)28)17-16-21(27)15-14-20-10-6-5-7-11-20/h3,5-8,10-11,16-17,19,21-25,27-29H,4,9,12-15,18H2,1-2H3/b8-3-,17-16+/t21?,22-,23-,24+,25-/m1/s1

Synthetic route

2-iodo-propane (75-30-9) + (5Z)-bimatoprost acid (38344-08-0) → 15α-hydroxy-17-phenyl-18,19,20-trinorprostaglandin F2α isopropyl ester (130209-76-6)

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetone for 10h; Ambient temperature;	80%

15-keto-17-phenyl-18,19,20-trinorprostaglandin F2α isopropyl ester (130209-77-7) → 15β-hydroxy-17-phenyl-18,19,20-trinorprostaglandin F2α isopropyl ester (130273-87-9) + 15α-hydroxy-17-phenyl-18,19,20-trinorprostaglandin F2α isopropyl ester (130209-76-6)

Conditions	Yield
With sodium tetrahydroborate; cerium(III) chloride In methanol; dichloromethane for 0.5h;	A 41% B 28%
With sodium tetrahydroborate; cerium(III) chloride 1.) MeOH, CH2Cl2, -78 deg C, 30 min, 2.) -78 deg C, 1 h; Yield given. Multistep reaction. Yields of byproduct given;

dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) → 15α-hydroxy-17-phenyl-18,19,20-trinorprostaglandin F2α isopropyl ester (130209-76-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) PhB(OH)2, molecular sieves 3A, 2.) PCC, AlCl3, 3.) DIPEA, LiCl, 4.) aq. H2O2 2: 1.) CeCl3*7H2O, 2.) NaBH4 / 1.) MeOH, CH2Cl2, -78 deg C, 30 min, 2.) -78 deg C, 1 h View Scheme

(Z)-7-((1R,2S,3R,5S)-3,5-Dihydroxy-2-hydroxymethyl-cyclopentyl)-hept-5-enoic acid isopropyl ester (177616-22-7) → 15α-hydroxy-17-phenyl-18,19,20-trinorprostaglandin F2α isopropyl ester (130209-76-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) PhB(OH)2, molecular sieves 3A, 2.) PCC, AlCl3, 3.) DIPEA, LiCl, 4.) aq. H2O2 2: 1.) CeCl3*7H2O, 2.) NaBH4 / 1.) MeOH, CH2Cl2, -78 deg C, 30 min, 2.) -78 deg C, 1 h View Scheme

(Z)-7-[(1R,2S,3R,5S)-2-(tert-Butyl-dimethyl-silanyloxymethyl)-3,5-dihydroxy-cyclopentyl]-hept-5-enoic acid isopropyl ester → 15α-hydroxy-17-phenyl-18,19,20-trinorprostaglandin F2α isopropyl ester (130209-76-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: NaHSO4*H2O / tetrahydrofuran; H2O / 13 h / Ambient temperature 2: 1.) PhB(OH)2, molecular sieves 3A, 2.) PCC, AlCl3, 3.) DIPEA, LiCl, 4.) aq. H2O2 3: 1.) CeCl3*7H2O, 2.) NaBH4 / 1.) MeOH, CH2Cl2, -78 deg C, 30 min, 2.) -78 deg C, 1 h View Scheme

Isopropyl (Z)-7-((1R,2R,3R,5S)-2-((3S,E)-3-(tert-butyldimethylsilyloxy)-5-phenyl-pent-1-enyl)-3-(tert-butyldimethylsilyloxy)-5-hydroxy-cyclopentyl)-hept-5-enoate (1190883-22-7) → 15α-hydroxy-17-phenyl-18,19,20-trinorprostaglandin F2α isopropyl ester (130209-76-6)

Conditions	Yield
With hydrogen fluoride In water; isopropyl alcohol Product distribution / selectivity;

isobutylamine (78-81-9) + 15α-hydroxy-17-phenyl-18,19,20-trinorprostaglandin F2α isopropyl ester (130209-76-6) → 17-phenyl-trinor-prostaglandin F2α isobutylamide (1131798-25-8)

Conditions	Yield
In methanol at 80℃; for 24 - 48h;	80%

15α-hydroxy-17-phenyl-18,19,20-trinorprostaglandin F2α isopropyl ester (130209-76-6) → 15-keto-17-phenyl-18,19,20-trinorprostaglandin F2α isopropyl ester (130209-77-7)

Conditions	Yield
With 2,3-dicyano-5,6-dichloro-p-benzoquinone In 1,4-dioxane for 24h; Ambient temperature;	76%

propylamine (107-10-8) + 15α-hydroxy-17-phenyl-18,19,20-trinorprostaglandin F2α isopropyl ester (130209-76-6) → bimatoprost (155206-00-1)

Conditions	Yield
In methanol at 90℃;	62%

15α-hydroxy-17-phenyl-18,19,20-trinorprostaglandin F2α isopropyl ester (130209-76-6) → (Z)-7-{(1R,2R,3R,5S)-3,5-Dihydroxy-2-[(2S,3S)-3-((S)-1-hydroxy-3-phenyl-propyl)-oxiranyl]-cyclopentyl}-hept-5-enoic acid isopropyl ester (177616-23-8) + (Z)-7-{(1R,2R,3R,5S)-3,5-Dihydroxy-2-[(2R,3R)-3-((S)-1-hydroxy-3-phenyl-propyl)-oxiranyl]-cyclopentyl}-hept-5-enoic acid isopropyl ester (177768-47-7)

Conditions	Yield
With titanium(IV) isopropylate; tert.-butylhydroperoxide; L-(+)-diisopropyl tartrate; dihydrogen peroxide; phenylboronic acid Product distribution; multistep reaction; stereoselective epoxidation of 17-phenyl-18,19,20-trinorprostaglandin F2α isopropyl ester and its 15-R epimer; regio- and stereoselective reactions of epoxides formed;
With titanium(IV) isopropylate; tert.-butylhydroperoxide; L-(+)-diisopropyl tartrate; dihydrogen peroxide; phenylboronic acid Yield given. Multistep reaction. Yields of byproduct given;
With titanium(IV) isopropylate; tert.-butylhydroperoxide; (-)-diisopropyl tartrate; dihydrogen peroxide; phenylboronic acid Yield given. Multistep reaction. Yields of byproduct given;

15α-hydroxy-17-phenyl-18,19,20-trinorprostaglandin F2α isopropyl ester (130209-76-6) → 15β-hydroxy-17-phenyl-18,19,20-trinorprostaglandin F2α isopropyl ester (130273-87-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 76 percent / DDQ / dioxane / 24 h / Ambient temperature 2: 41 percent / NaBH4, CeCl3*7H2O / CH2Cl2; methanol / 0.5 h View Scheme

Upstream product

• 75-30-9 2-iodo-propane 
• 38344-08-0 (5Z)-bimatoprost acid 
• 1190883-22-7 Isopropyl (Z)-7-((1R,2R,3R,5S)-2-((3S,E)-3-(tert-butyldimethylsilyloxy)-5-phenyl-pent-1-enyl)-3-(tert-butyldimethylsilyloxy)-5-hydroxy-cyclopentyl)-hept-5-enoate 
• 130209-77-7 15-keto-17-phenyl-18,19,20-trinorprostaglandin F_2α isopropyl ester 
• 177616-22-7 (Z)-7-((1R,2S,3R,5S)-3,5-Dihydroxy-2-hydroxymethyl-cyclopentyl)-hept-5-enoic acid isopropyl ester 
• 41162-19-0 dimethyl(2-oxo-4-phenylbutyl)phosphonate 

Downstream Products

• 1131798-25-8 17-phenyl-trinor-prostaglandin F2α isobutylamide 
• 155206-00-1 bimatoprost 
• 130273-87-9 15β-hydroxy-17-phenyl-18,19,20-trinorprostaglandin F_2α isopropyl ester 
• 177616-23-8 (Z)-7-{(1R,2R,3R,5S)-3,5-Dihydroxy-2-[(2S,3S)-3-((S)-1-hydroxy-3-phenyl-propyl)-oxiranyl]-cyclopentyl}-hept-5-enoic acid isopropyl ester 
• 177768-47-7 (Z)-7-{(1R,2R,3R,5S)-3,5-Dihydroxy-2-[(2R,3R)-3-((S)-1-hydroxy-3-phenyl-propyl)-oxiranyl]-cyclopentyl}-hept-5-enoic acid isopropyl ester 
• 130209-77-7 15-keto-17-phenyl-18,19,20-trinorprostaglandin F_2α isopropyl ester 

Relevant academic research and scientific papers

Process for the Preparation of Prostaglandin Analogues and Intermediates Thereof

The present application provides intermediates for preparing prostaglandin analogues and processes for preparing prostaglandin analogues and intermediates thereof. The intermediates include: A compound of formula (6): R1 represents H, C1-C5-alkyl, or benzyl, in particular isopropyl.

9,11-cycloendoperoxide pro-drugs of prostaglandin analogues for treatment of ocular hypertension and glaucoma

9,11-Cycloendoperoxide derivatives of biologically active prostaglandin analogs, and particularly of the ocular hypotensive drugs Bimatoprost, Latanaprost, Unoprostone, Travoprost and prostaglandin H2 1-ethanolamide or of structurally closely related analogs, are pro-drugs which hydrolyze under physiological conditions to provide prostaglandin analogues that are capable of providing sustained ocular and other in vivo concentrations of the respective drugs. The compounds of the invention have the formula shown below where the variables have the meaning defined in the specification.

Regio- and stereoselective reactions of 17-phenyl-18,19,20-trinorprostaglandin F2α isopropyl ester

Novel prostaglandin F2α derivatives, functionalized at C13 and C14, have been prepared. 17-Phenyl-18,19,20-trinorprostaglandin F2α isopropyl ester [(15S)-1] and its epimer [(15A)-1] were stereoselectively epoxidized, using Sharpless conditions, to produce each of the four diastereomeric epoxides (15S)-2, (15S)-3, (15R)-2, and (15R)-3. Treatment of the four epoxides with LiOH stereospecifically-produced the pentahydroxy substituted analogues 12 and 13. Alternatively, epoxides 2 and 3 were allowed to react with thiophenolate ion. The attack of the sulfur nucleophile on the epoxide occurred at either C13 or C14 depending on the stereochemistry of the epoxide and of C15.

Phenyl-Substituted Prostaglandins: Potent and Selective Antiglaucoma Agents

A series of phenyl-substituted analoques of prostaglandin F2α (PGF2α) were prepared and evaluated for ocular hypotensive effect and side effects in different animal models.In addition, the activity of the analogues on FP receptors was studied in vitro.The results were compared with those of PGF2α and its isopropyl ester.The phenyl-substituted PGF2α analogues exhibited good intraocular pressure reducing effect, were more selective, and exhibited a much higher therapeutic index in the eye than PGF2α or its isopropyl ester.The analogues exhibited high activity on FP receptors in a stereoselective manner for the 15a-hydroxyl group.