Concise synthesis of guanidine-containing heterocycles using the Biginelli reaction.
Two general methods for the synthesis of 2-imino-5-carboxy-3,4-dihydropyrimidines were developed using the three-component Biginelli reaction. The first method utilizes pyrazole carboxamidine, a beta-ketoester, and an aldehyde in an initial Biginelli reaction. After Boc protection, these products undergo aminolysis and acidic deprotection to generate 2-imino-5-carboxy-3,4-dihydropyrimidines in a four-step sequence. The second method utilizes a triazone-protected guanidine, a beta-ketoester, and an aldehyde in a Biginelli reaction. Acidic cleavage of the triazone yields 2-imino-5-carboxy-3,4-dihydropyrimidines in a two-step sequence. We also describe the further elaboration of several of these products using a tethered Biginelli reaction to give triazaacenaphthalene structures similar to those found in crambescidin and batzelladine alkaloids.
Nilsson
Bradley L
BL
Department of Chemistry, University of California, Irvine, California 92697-2025, USA.
Overman
Larry E
LE
D000447:Aldehydes / Q000737:chemistry; D000470:Alkaloids / Q000138:chemical synthesis; D019791:Guanidine / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D008722:Methods; D011720:Pyrazoles / Q000737:chemistry
D000447:Aldehydes; D000470:Alkaloids; D006571:Heterocyclic Compounds; D011720:Pyrazoles; C107726:pyrazole-1-carboxamidine; D019791:Guanidine