Carboprost
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Carboprost (Hemabate)
Effective Against
Carboprost is a synthetic prostaglandin analogue of PGF2α (specifically, it is 15-methyl-PGF2α) with oxytocic properties (meaning it acts by causing the uterus to contract the way it does during labor and also helps the cervix to dilate).
Cost
From Cayman Chemical: 100 USD (1g) or 450 USD (5g)
Reported Routes of Synthesis
Addition of Grignard reagent CH3MgCl to the ketone (I) in toluene or xylene or THF followed by preparative HPLC leads to alcohol (II), which undergoes reduction with DIBAL in THF to give lactol (III). Wittig reaction of lactol (III) with the ylide formed by the reaction of 4-carboxybutyltriphenyl-phosphonium bromide (IV) either with NaH or NaNH2, DMSO affords free acid (V) of the title compound (1).
Improved method for the Wittig reaction in the preparation of carboprost. AstraZeneca Pharma India Ltd., AstraZeneca plc, WO 2008081191
Grignard reaction of tris(trimethylsilyl) derivative of 15-oxo-PGF2alpha (I) with CH3MgBr in Et2O gives a mixture of compounds 15(R) and 15(S)-methyl-PGF2alpha, which is then subsequently treated with CH2N2 and subjected to chromatography to afford 15(S)-methyl derivative (II). Saponification of methyl ester (II) by means of KOH in MeOH/H2O furnishes the free acid (III) of the title compound (1,2).
Process for production of novel prostaglandin analogs. Pfizer Inc. DE 2121980, GB 1314291, GB 1314293, DE 2166630, CA 0959485
15-Methyl and 15-ethyl prostaglandin analogs Pfizer Inc. US 3728382, JP 1977017449, JP 1978084945
Debenzoylation of benzoyl derivative (I) by means of NaOMe in MeOH gives alcohol (II), which is treated with Et2NSiMe3 in acetone to yield trimethylsilyloxy derivative (III). Reduction of lactone (III) with DIBAL in toluene leads to diol (IV). Reduction of lactone (I) or (II) with DIBAL in THF affords diol (V) or (VI) respectively. Wittig reaction of either trimethylsilyloxy derivative (IV) or benzoyl derivative (V) or triol (VI) with 4-carboxybutyltriphenyl-phosphonium bromide (VII) using NaH, DMSO furnishes racemate (VIII) of the title compound (1).
Yankee, E.W.; Axen, U.; Bundy, G.L.
Prostaglandins: A general article about prostaglandins and some biological and chemical synthesis techniques
Collins, Paul W. 2000. Prostaglandins. Kirk-Othmer Encyclopedia of Chemical Technology.