Synthese Of Pyrrolo[1, 2-a] Pyrazine-1, 4-dione Alkyl Derivatives

Pyrrole alkaloids is one of the important branches of alkaloid chemistry, many kinds of alkaloids which include pyrrolo[1,2-a]pyrazine-1,4-dione structural element show notable bioactivities, such as anti-bacterium anti-inflammatory, antitumor, antivirus, and anti-diabetes, et al. The thesis describe the synthesis of bioactivity substances of 3,3-dialkyl-2-hydropyrrolo[1,2-a]pyrazine-1,4-diones by refinement multi-step reactions with the economic and convenient compounds of pyrrole andα-amino acid as starting materials. A series of N-(pyrrole-2-carbonyl)-α-amino acid methyl esters as synthetic intermediates were synthesized by acylation of pyrrole with trichloroacetyl chloride, followed by condensation with a-amino acid methyl esters. Ten novel 3,3-dialkyl-2-hydropyrrolo[1,2-a]pyrazine-1,4-diones were obtained in 77.3～91% yields by "one-pot" reaction of the above intermediates and alkylation reagents RX. The reaction mechanism about the synthesis of 3,3-dialkyl-2-hydropyr-rolo[1,2-a]pyrazine-1,4-diones was researched preliminarily also. We concluded the reaction process is that the structure of pyrrolo[1,2-a]pyrazine-1,4-dione was generated by intramolecular cyclocondensation of N-(pyrrole-2-carbonyl)-α-amino acid methyl esters at first, then the cyclocondensation products reacted with alkylation reagents RX, forming the alkylates.Most of the above products prepared by the studies are new compounds without document data existed to reference. All of the synthetic products were purified by recrystallization or chromatography, and their structures were determined by means of IR,1HNMR, MS combination with the chemical and physical properties. Furthermore, some of these product's structures were confirmed by single-crystal X-ray diffraction. Reaction conditions, reaction mechanisms of the syntheses were discussed and explained in detail, and the spectral data also.