Asymmetric Alkylation In The Synthesis Of Spiro [Pyrrolidine-2,3’-quinolione]

Quinoline compounds is a kind of important intermediates, it has importantapplications in medicine, dye, pesticide, chemical fertilizer, antioxidants, food and feedadditives, ect. Especially, the chiral spirocompounds with2(1H)-quinolione tend tohave a variety of biological activity. It is widespread invarious alkaloids and molecularstrcture of drug with different pharmacological action, and it has a stable of three-ringsystem and intramolecular lactam bond, some can be used as the source of the druglead compounds. The introduction of different substituent or side chain on the ring canproduce different pharmacological activities, such as resistance to mental disorders,anti-tumor, anti-platelet aggregation, positive inotropic, allergy and anti-ulcer effect. Inthis paper, pure chiral compounds spiro[pyrrolidine-2,3’-quinolione] was synthesizedwith proline as raw materials in the asymmetric synthesis method.This paper will be divided into two parts: the first part, spiro[pyrrolidine-2,3’-quinolione] was synthesized from racemic proline and R(S-)-proline as the rawmaterials by esterification, reaction group-protecting, C-alkylation, nitroreduction andcyclization. the method is simple in operation, high yield and versatility.The second part, chiralspiro[pyrrolidine-2,3’-quinolione] was synthesized fromR(S-)-proline as the raw materials by acid aldehyde condensation reaction,C-alkylation, hydrolysis, esterification, reaction group-protecting, nitroreduction andcyclization. In this part, the carbon alkylation reaction is the key step in the control ofchiral, LDA, KHMDS, LiHMDS, NaH was investigated, the experimental results showthat the asymmetric carbon atom. Has no racemization when the LDA was used asalkylation reagent, and the products of two configurations are enantiomers, S-:[α]DRT=+334.3(MeOH, c:0.134g/100ml),R-:[α]DRT=-338.89(MeOH, c:0.0744g/100ml). The final product with an ee value up to97%was achieved. A simple synthetic method ofchiral quinlione spiro-compound was obtained, which is significative for furtherstudies of their activity.