A convenient base-mediated two-step synthesis of cotinine analogs and a one-pot base-free synthesis of iso-cotinine derivatives featuring an Ugi-4CR/cyclization protocol are reported. These approaches exploit the reactivity of the peptidyl position present in the Ugi adducts, allowing the facile construction of the γ-lactam core, as well as the introduction of a N-substituted methyl group into the analogs in a straightforward manner. A plausible mechanism for the cyclization step is discussed.

An Efficient Microwave-Assisted Synthesis of Cotinine and Iso-Cotinine Analogues from an Ugi-4CR Approach. -The cotinine analogues [e.g. (VI)] are synthesized from 3-pyridinylaldehydes [e.g. (I)] in two steps under base-mediated reaction conditions. The iso-cotinine analogues are synthesized from 2-or 4-pyridinylaldehydes [e.g. (XIII)] in one step under base-free conditions. -(POLINDARA-GARCIA, L. A.; MONTESINOS-MIGUEL, D.; VAZQUEZ*, A.; Org. Biomol. Chem. 13 (2015) 34, 9065-9071, http://dx.doi.org/10.1039/C5OB01170A ; Dep. Quim. Org., Fac. Quim., Univ. Natl. Auton. Mex., Coyoacan, 04510 Mexico, Mex.; Eng.) -L. Grundl 05-125