169873-06-7

Upstream product

• 169771-75-9 (S)-(+)-tetrahydrofuran-2-yl acetoacetate 
• 552-89-6 2-nitro-benzaldehyde 
• 97-99-4 (S)-(tetrahydrofuran-2-yl)methanol 
• 87392-07-2 (S)-tetrahydro-2-furoic acid 
• 87324-01-4 (S)-(+)-methyl tetrahydrofuran-2-carboxylate 
• 16874-33-2 tetrahydro-2-furancarboxylic acid 
• 97-99-4 Tetrahydrofurfuryl alcohol 

Downstream Products

• 138661-03-7 (RS)-furnidipine 
• 138661-03-7 (SS)-furnidipine 

Relevant academic research and scientific papers

Synthesis and Chromatographic Separation of the Stereoisomers of Furnidipine

The four stereoisomers of methyl tetrahydrofuran-2-ylmethyl 2,6-dimethyl-4-(o-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate (furnidipine), have been synthesized and separated by chiral chromatography using D-phenylglycine as chiral stationary phase.Enantiomeric purity of stereoisomers is determined by HPLC-CSP technique and configurations deduced via X-ray crystallography.

Synthesis, Structure, and Pharmacological Evaluation of the Stereoisomers of Furnidipine

The synthesis and pharmacological activities of the four stereoisomers of methyl tetrahydrofuran-2-ylmethyl 2,6-dimethyl-4-(2'-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate (furnidipine) are reported.The four isomers were synthesized by a modified Hantzsch synthesis by reaction of (-)- or (+)-tetrahydrofuran-2-ylmethyl 3-aminocrotonate and methyl 2-acetoacetate or, alternatively, by reaction of (-)- or (+)-tetrahydrofuran-2-ylmethyl 2-acetoacetate and methyl 3-aminocrotonate.The 1:1 diasteromeric mixture thus obtained were separated by chromatography, using poly(D-phenylglycine) as the chiral stationary phase.The enantiomeric purity of the stereoisomers was determined by high-performance liquid chromatography-chiral stationary phase technique (HPLC-CSP).Attempts to obtain crystals of a single stereoisomer failed in different solvent, while methanol crystallization of the product obtained from (+/-)-tetrahydrofuran-2-ylmethyl 2-acetoacetate and methyl 3-aminocrotonate yielded good-quality crystals of the most insoluble racemate which proved to be a mixture of the (SS)/(RR) enantiomers by X-ray crystaloography.Conformational analysis of the stereoisomers, assuming rotation of the aryl substituent and ester groups, shows small energy differences (about 4 kcal*mol-1) between the most and the least favorable conformations.Binding studies were performed using isradipine as a reference ligand.The results showed stereospecificity of the furnidipine isomers in brain, ileum, and cardiac tissues, the (SS) and (SR)-isomers clearly being more potent than their (RR)- and (RS)-enantiomers.The (SS)- and (SR)-isomers were also more selective on cerebral tissue when compared with ileal and cardiac preparations.