Pyrrolidine Derivatives Research

Pyrrolidine derivatives are the key intermediate to synthesize quinolone antibacterial drugs, antihypertensive drugs, hypoglycemic drugs, and antineoplastic agents. More and more attentions have paid for them, particularly, it becomes a research hot that catalytic stereoselective synthesis of poly functional pyrrolidine derivatives in recent years at home and abroad.Five typical pyrrolidine derivatives have been synthesized,and some of their synthesis schemes were optimized.Ganerally, we choose cheap raw materials and simple synthetic.It's better to know other simillar pyrrolidine derivatives where synthesized one of them. Specific research results are as follows:By using ethyl acrylate and benzyl amine as starting materials, we synthesized3-amino-pyrrolidine dihydrochloride salt after addition, substitution, cyclization, decarboxylation, and reduction, and investigated the two critical steps (the Dieckmann cyclization and the reduction of oxime).Cyclization reaction takes place between L-malic acid and benzylamine, after reducting thire product by using LAH/THF, we got the crude product (S)-N-benzyl3-hydroxypyrrolidine, then resoluted them by using resolution agent Ts-L-Phe.We investigated the reduction step and the resolution step.Using hexamethylenetetramine as the source of amino, reacted with cis-1,4-dichloro-2-butene, it takes two steps to synthesize N-Boc-3-pyrroline. Following cyclazition and ring-open to get (±)-trans-N-Boc-3-benzyl amino-4-hydroxy-pyrrolidine.We use L-mandelic acid to resolute the racemic mixture to get the final product,(3S,4S)-N-Boc-3-benzyl amino-4-hydroxy-pyrrolidine,and investigated the solvent effects in the last two steps.Without solvent, hexahydrophthalic anhydride reacted with urea at high-temperature to get cis-hexahydro phthalimide, then the product was reducted by LAH/THF system to get the final product cis-Octahydroisoindole.We use glycine ethyl ester hydrochloride and acrylonitrile as raw materials, through addition, protecting the sec-amino and Dieckmann cyclization to get1-Boc-3-cyano-4-pyrrolidone.