Asymmetric Synthesis And Structural Characterization Of Multi Functional Group Of Chiral Aziridine Derivatives

The versatility and high reactivity of the chiral aziridines make them attractiveintermediates for the synthesis of various types of organic molecules, such as chiralamines, aminoacids, amino alcohols, alkaloid,β-lactamic, polymers. Moreover, chiralaziridines have been utilized as ligands and auxiliaries in asymmetric synthesis. Anumber of synthetic aziridines have found biological applications as antitumor agents,antibiotics, and as enzyme inhibitors. Several naturally occurring aziridines have beenshown exhibit antibiotic and antitumor activity. Despite these interests, the reports ofthe synthetic methods for these compounds are rather limited. In this paper, somechiral aziridine derivatives with novel structure have been synthesized based on thepatented applied prospects and the main results as follows:1. Chiral sythons for 4-(L)-(1'R,2'S,5'R)-menthyloxy-butenolide 3 and 4-(L)-(1'R,2'S,5'R)-menthyloxy-2-bromo-butenolide 5a were synthesized via photochemicalreaction, acetalization, bromine addition and elimination reaction for hydrogenbromide using furfural, a very cheap material.2.4-(R)-(1'R,2'S,5'R)-menthyloxy-butyrolacto[3,4-b]-2(S)-6(R)-1-N-alkyl-azirid-ines 7 were synthesized via tandem asymmetric Michael addition/intramolecularnucleophilic substitution of 4-(L)-(1'R,2'S,5'R)-menthyloxy-2-bromo-butenolide 5awith nitrogen nucleophilic reagents by using DMSO as solvent and triethylamine asalkali catalyst under the condition of 60～65℃refluxing. Chiral 4-hydroxy-4-butyrolactam fused aziridine was synthesized by 4-(R)-(1'R,2'S,5'R)-menthyloxy-butyrolacto[3,4-b]-2(S)-6(R)-1-N-alkyl-aziridines with cyclohexane under roomtemperature.3. Chiral compound spiro[1-bromo-4-L-menthyloxy-5-oxo-6-oxa-biscyclo [3.1.0]-hexane-2,3'-(4'-diphenylmenthanol-5'-L-menthyloxy-butyrolactone)]was synthesizedvia Michael addition reaction of 4-(L)-(1'R,2'S,5'R)-menthyloxy-2-bromo-butenolidewith diphenyl menthanol by using acetonitrile as solvent, K₂CO₃ as alkali medium and TBAB as phase transfer catalyst under the condition of nitrogen gas atmosphere. Anovel chiral compound spiro[1-bromo-4-hydroxy-5-(N-cyclohexyl)-butyrolactam-6-oxa-biscyclo[3.1.0]-hexane-2,3'-(4'-diphenylmenthanol-5'-L-menthyl-oxy-butyrolac-tone) was synthesized by spiro[1-bromo-4-L-menthyloxy-5-oxo-6-oxa-biscyclo[3.1.0]-hexane-2,3'-(4'-diphenylmenthanol-5'-L-menthyloxy-butyrolacto-ne)] with cyclohex-ane under room temperature.4. A novel chiral compound 4-(R)-(1'R,2'S,5'R)-menthyloxy-3-(R)-hexahydropy-ridine-butyrolactone was synthesized via Michael addition reaction of 4-(L)-(1'R,2'S,5'R)-menthyloxy-butenolide with hexahydropyridine by using acetonitrile assolvent, K₂CO₃ as alkali medium and TBAB as phase transfer catalyst under thecondition of nitrogen gas atmosphere.5. A novel morphine derivative was synthesized by Michael addition/internalnucleophilic substitution of 4-(L)-(1'R,2'S,5'R)-menthyloxy-butenolide with phenyl-glyalcohol under mild condition. 4-(L)-(1'R,2'S,5'R)-menthyloxy-3-benzylamine-butenolide was synthesized via Michael addition/intramolecular elimination reactionby using 4-(L)-(1'R,2'S,5'R)-menthyloxy-2-bromo-butenolide with benzylamine undernitrogen gas atmosphere.6. Obtained chiral 4'-(R)-butenolide-4-(R)-butenolide via photochemical reaction,acetalization and etc. by using furfural, a very cheap material.7. Obtained six kinds of phenylhydrazones under the condition of ice bath byusing aniline diazonium salts and active methylene compounds.Componds of 8, 10, 11, 12, 13, 14 and 15 were characterized by elementalanalysis, IR, NMR and MS. Their chemical structures and spatial configurations ofcompounds 8a, 10, 11, 12, 13, 14 and 15e were also determined by X-ray crystallinediffraction.