Stiripentol
From The Cure For The Needy
Contents |
Stiripentol (Diacomit)
Effective Against
Stirpentol has both direct anticonvulsant effects, as well as indirect effects through its tendency to raise blood levels of other anticonvulsants. The mechanism by which it directly affects seizures is unknown, but it appears to increase GABA levels in the brain. It does not appear to interact with either GABA-A or GABA-B receptors, so the effect on GABA may occur through prevention of synaptosomal reuptake, or inhibition of GABA transaminase.
Cost
"As of 2/16/2009, the retail cost of stiripentol from Caligor Pharmacy is $621.18 for the 500mg formulation, quantity sixty (#60; capsules or sachets)."
Obtained from https://braininstitute.mch.com/w/index.php?title=Stiripentol&oldid=4299
Reported Route of Synthesis
The condensation of 3,4-methylenedioxybenzaldehyde (I) with 3,3-dimethyl-2-butanone (II) by means of NaOH in ethanol-water gives 4,4-dimethyl-1-[(3,4-methylenedioxy) phenyl ]-1-penten-3-one (III), which is reduced with NaBH4 in methanol.
Castaner, J.; Hillier, K. Stiripentol. Drugs Fut 1980, 5(8): 413
Astoin, J.; et al.; Action of new ethylenic alcohols on the central nervous system. Eur J Med Chem - Chim Ther 1978, 13(1), 41-47
Cost of Starting Materials and Selected Reagents:
Starting Material Piperonal from Sigma-Aldrich: 25.7 USD (100g)
3,3-Dimethyl-2-butanone from Sigma-Aldrich: 20.7 USD (5 mL)
Sodium Borohydride from Sigma-Aldrich: 79.2 USD (100g)
Description: The synthesis of [14]-labeled stiripentol has been published: The reaction of 3,4-methylenedioxybromobenzene (I) with 14CO2 by means of butyllithium in ether gives 3,4-methylenedioxybenzoic acid (II), which is reduced with LiAlH4 to the corresponding benzyl alcohol (III). Oxidation of (III) with CrO3-pyridine affords the aldehyde (IV), which is condensed with methyl tert-butyl ketone (V) by means of NaOH in refluxing ethanol to give the labeled pentanone (VI) . Finally, this compound is reduced to [14C]-labeled stiripentol with NaBH4 in methanol.
Reference: Lepage, F. Veyre, A.; Madelmont, JC; Labarre, P.; Maurizis, JC; Rapp, M.; Dupuy, JM; Labelling by 14C and 3H of 4,4-dimethyl-1-(3,4 -- methylenedioxyphenyl)-1-pentene-3-ol or stiripentol. J Label Compd Radiopharm 1992, 31(11), 961
Obtained from http://www.chemdrug.com/ Specific, translated page available here.
Cost of Starting Materials and Selected Reagents:
Starting Material 1-Bromo-3,4-(methylenedioxy)benzene from Sigma-Aldrich: 87.2 USD (25g)
Butyllithium Solution (2 M) in cyclohexane from Sigma-Aldrich: 31.1 USD (100 mL)
Carbon Dioxide from Sigma-Aldrich: 192 USD (227G)
Lithium Aluminum Hydride from Sigma-Aldrich: 28.5 USD (10g)
Chromium(VI) oxide from Sigma-Aldrich: 227 USD (1 kg)
Pyridine from Sigma-Aldrich: 66.5 USD (100mL)
3,3-Dimethyl-2-butanone from Sigma-Aldrich: 20.7 USD (5 mL)
Sodium Hydroxide (10 M in H2O) from Sigma-Aldrich: 61.6 USD (100 mL)
Sodium Borohydride from Sigma-Aldrich: 79.2 USD (100g)