Eflornithine
From The Cure For The Needy
Contents |
Eflornithine (Ornidyl)
Effective Against
African Trypanosomiasis (sleeping sickness), especially the West African form (Trypanosoma brucei gambiense)
Eflornithine appears to kill trypanosomes by acting as a suicide inhibitor of the enzyme ornithine decarboxylase (EC 4.1.1.17), this enzyme regulates cell division by catalysing the first step in polyamine biosynthesis. As the inhibitor has a low half-life in humans, it is broken down quickly while the parasite cannot metabolise it quickly enough. This means that it preferentially harms the parasite.
Cost
From Sigma-Aldrich: 127.50 USD (25mg) or 394 USD (100mg) for the hydrochloride hydrate
From Tocris Bioscience: 44 USD (10 mg) or 195 USD (50mg)
Reported Routes of Synthesis
By reaction of N2, N5-dibenzylidinolysine methly ester (I), with chlorodifluoromethane (II) in the presence of lithium diisopropylamide, followed by acid hydrolysis of the ester. Isolated as the monohydrochloride salt, monohydrate.
Gale, G.R. D,L-alpha-Difluoromethyl ornithine. Drugs Fut 1981, 6(3): 142
Schijvenaars, M.; Franke, B.; Mariman, ECM; Steegers-Theunissen, R.; Willemen, J.; Groenen, P.; Klootwijk, R.; Hol, F.; D, L-alpha-Difluoromethyl ornithine - RMI 71782. Product data sheet, center de recherche Merrell, Strasbourg Cedex 2002, Abst 1027
Cost of Starting Materials and Selected Reagents:
Starting Material Methyl 2,5-bis(benzylideneamino)pentanoate pricing not available from Sigma-Aldrich
Starting Material Chlorodifluoromethane pricing not available from Sigma-Aldrich
- Chloroform from Sigma-Aldrich: 22.4 USD (25 mL)
- Hydrofluoric acid from Sigma-Aldrich: 63.5 USD (100 mL)
Lithium diisopropylamide from Sigma-Aldrich: 146 USD (25 g)
Hydrochloric acid from Sigma-Aldrich: 46.5 USD (100 mL)
The optical resolution of 2,5-diamino-2-(difluoromethyl) pentanoic acid is performed as follows: The cyclization of its corresponding methyl ester (I) by means of sodium methoxide in methanol gives the racemic piperidone (II), which is submitted to optical resolution with (-)-binaphthylphosphoric acid yielding after crystallization and acidification with HCl the (+) and (-) piperidones (III) and (IV). Finally, both compounds are treated with refluxing 6N HCl to afford the target enantiomers.
Jung, M.; Bey, P. (Aventis Pharma SA); 2-(Difluoromethyl)-2,5-diaminopentanoic acid. US 4413141
Cost of Starting Materials and Selected Reagents:
Starting Material Methyl 2,5-diamino-2-(difluoromethyl)pentanoate pricing not available from Sigma-Aldrich
Hydrochloric acid from Sigma-Aldrich: 46.5 USD (100 mL)
Sodium methoxide from Sigma-Aldrich: 20.1 USD (25 g)
(-)-binaphthylphosphoric acid (BNPA) pricing not available from Sigma-Aldrich