engleski

Synthesis, Separation and Absolute Configuration Determination by ECD Spectroscopy and TDDFT Calculations of 3-Amino-beta- lactams and Derived Guanidines

Four isomeric chiral 3-amino-beta-lactams 4 with p-fluorophenyl and p-methoxyphenyl substituents at N and C-4 positions, similar to the cholesterol absorption inhibitor ezetimibe, have been prepared as diastereomerically and enantiomerically pure compounds by ester enolate/imine cyclocondensation. The same route afforded analogues with a 1, 3-benzodioxole instead of the p- methoxyphenyl group. Moreover, beta-lactams 4a, b were converted into benzoylguanidine derivatives. The series of chiral beta-lactams and beta-lactam guanidines was characterized by electronic circular dichroism (ECD) spectroscopy, and their absolute configurations were assigned based on ECD TDDFT calculations. The calculations also demonstrated that the beta-lactam sector and helicity rules cannot be applied to beta-lactams appended with aromatic chromophores such as the present ezetimibe analogues.

Circular dichroism ; Cyclization ; Enols ; Enantioselectivity ; Lactams ; Density functional calculations

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