Tetrahydro-4(1H)-pyrimidinone ring formation of bellenamine, a biogenic amine, with carbonyl compounds

Article abstract of DOI:10.1246/bcsj.67.1904

Bellenamine, (R)-3,6-diamino-N-(aminomethyl)hexanamide in a neutral aqueous solution at 37°C formed a new tetrahydro-4(1H)-pyrimidinone compound, N¹,N³-methylenebellenamine by the reaction with self-generated formaldehyde. The structure was elucidated by NMR spectral analyses. Two tetrahydro-4(1H)-pyrimidinone compounds, N¹,N³-methylenebellenamine and (R)-6-(3-aminopropyl)tetrahydro-4(1H)-pyrimidinone (tentatively named cyclized bellenamine) were synthesized from bellenamine and D-β-lysinamide, respectively, with an equimolar amount of formalin in good yields. However, formation of a 5-membered ring 4-imidazolidinone compound by the reaction of L-lysinamide with formalin was a very low yield. Reaction of bellenamine with acetaldehyde gave a mixture of four diastereomeric aldol adducts. By the reaction with acetone or diacetone alcohol, two stereoisomeric diacetone adducts, (2R,9aS)- and (2R,9aR)-2-(3-aminopropyl)-8,8,9a-trimethyloctahydro-4H-pyrimido[1,6α ]pyrimidin-4-one, were obtained. Although these adducts were difficult to separate, the (2R,9aR) diastereomer was more stable than the other in acidic aqueous solution.