Tafluprost

Base Information

• Chemical Name: Tafluprost
• CAS No.: 209860-87-7
• Molecular Formula: C₂₅H₃₄F₂O₅
• Molecular Weight: 452.539
• European Community (EC) Number: 682-458-7
• UNII: 1O6WQ6T7G3
• DSSTox Substance ID: DTXSID401021504
• Nikkaji Number: J1.975.790K
• Wikipedia: Tafluprost
• Wikidata: Q2139543
• NCI Thesaurus Code: C87385
• RXCUI: 1244607
• Pharos Ligand ID: H348SPT32H76
• Metabolomics Workbench ID: 43728
• ChEMBL ID: CHEMBL1963683
• Mol file: 209860-87-7.mol

Synonyms:1-methylethyl (5Z)-7-((1R,2R, 3R,5S)-2-((1E)-3,3-difluoro-4-phenoxy -1-butenyl)-3,5-dihydroxycyclopentyl)-5-heptenoate;AFP-168;tafluprost

Chemical Property of Tafluprost

Chemical Property:

• Vapor Pressure: 4.62E-13mmHg at 25°C
• Refractive Index: 1.548
• Boiling Point: 552.9ºC at 760mmHg
• PKA: 14.48±0.70(Predicted)
• Flash Point: 288.2°C
• PSA: 75.99000
• Density: 1.186 g/cm³
• LogP: 4.68300
• Storage Temp.: 2-8°C
• XLogP3: 4.5
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 13
• Exact Mass: 452.23743050
• Heavy Atom Count: 32
• Complexity: 614

Purity/Quality:

98.0% ^*data from raw suppliers

Tafluprost ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(C)OC(=O)CCCC=CCC1C(CC(C1C=CC(COC2=CC=CC=C2)(F)F)O)O
• Isomeric SMILES: CC(C)OC(=O)CCC/C=C\C[C@H]1[C@H](C[C@H]([C@@H]1/C=C/C(COC2=CC=CC=C2)(F)F)O)O
• Recent ClinicalTrials: Prospective, Single Center Switching Study of 0.0015% Tafluprost Ophthalmic Solution in Primary Open-angle Glaucoma and Ocular Hypertension Patients With Corneal Disorders (Switching From 0.005% Latanoprost Ophthalmic Solution)
• Recent EU Clinical Trials: Selective laser trabeculoplasty versus eye drops for first line treatment of exfoliation ocular hypertension or glaucoma: a randomised clinical trial
• Recent NIPH Clinical Trials: Efficacy and safety of a switch to latanoprost 0.005% + timolol maleate 0.5% fixed combination eyedrops from tafluprost 0.0015% monotherapy.
• Description: Glaucoma is second only to cataracts as a causative factor of blindness. By 2010, it is estimated that approximately 60 million people worldwide will be afflicted by glaucoma, so effective treatments should garner a large market. PG analogs have been widely used for lowering IOP by increasing uveoscleral outflow through agonism of the prostanoid FP receptor, and currently marketed versions include latanoprost, unoprostone isopropyl ester, bimatoprost, and travoprost. Compared to the carboxylic acid of latanaprost (Ki=4.7 nM), the carboxylic acid of tafluprost displayed a 10-fold greater affinity for the prostanoid FP receptor (Ki=0.4 nM). The synthesis of tafluprost begins with a Wittig condensation of the protected bicyclic lactone carbaldehyde with a dimethyl phosphonate ketone derivative.Compared to the carboxylic acid of latanaprost (Ki 4.7 nM), the carboxylic acid of tafluprost displayed a 10-fold greater affinity for the prostanoid FP receptor (Ki 0.4 nM). The synthesis of tafluprost begins with a Wittig condensation of the protected bicyclic lactone carbaldehyde with a dimethyl phosphonate ketone derivative. The bottom appendage is then completed by the fluorination of the ketone with morpholino-sulfur trifluoride. Hydrolysis of the benzoate ester protecting group liberates the hydroxy group, and reduction of the lactone is accomplished with aluminum hydride to generate the lactol. Condensation of this intermediate with the phosphonium salt of the acid side chain generates the free acid, or active ingredient, which is subsequently esterified with 2-iodopropane in the presence of DBU. .
• Uses: Tafluprost is a novel prostanoid used in the treatment of glaucoma and is the first prostanoid to be released in a preservative free-formula.

Technology Process of Tafluprost

There total 66 articles about Tafluprost which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 94.3%

2-iodo-propane (75-30-9) + C22H28F2O5*C10H17N → tafluprost (209860-87-7)

Guidance literature:

With 1,8-diazabicyclo[5.4.0]undec-7-ene; In tert-butyl methyl ether; at 56 ℃;

Reference yield: 93.2%

2-iodo-propane (75-30-9) + C22H28F2O5 → tafluprost (209860-87-7)

Guidance literature:

With 1,8-diazabicyclo[5.4.0]undec-7-ene; In acetone; at 55 ℃; Reagent/catalyst; Solvent;

Reference yield: 92.5%

propan-2-yl (5Z)-7-[(1R,2R,3R,5S)-3,5-bis(acetyloxy)-2-[(1E)-3,3-difluoro-4-phenoxybut-1-en-1-yl]cyclopentyl]hept-5-enoate (1559057-73-6) → tafluprost (209860-87-7)

Guidance literature:

With sodium; In isopropyl alcohol; at -20 ℃; for 24h; Temperature;

upstream raw materials:

2-iodo-propane

AFP-172

dimethyl (3-phenoxy-2-oxopropyl)phosphonate

(1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one

Refernces

• 1、 -. "Method for purifying tafluprost". Paragraph 0101-0103. . Retrieved 2021/05/29.
• 2、 Fletcher, Stephen P.,Goetzke, F. Wieland,Ku?era, Roman. "An Asymmetric Suzuki-Miyaura Approach to Prostaglandins: Synthesis of Tafluprost". supporting information. . Retrieved 2020/04/09.