Traceless solid-phase synthesis of 1,3,7,8-tetrasubstituted xanthine (1,3,7,8-tetrasubstituted 1H-purine-2,6(3H,7H)-dione) derivatives has been developed. The solid-phase synthetic route began on a solid supported N'-cyano-N-substituted carbamimidothioate, which was prepared from cyanamide, isothiocyanate, and Merrifield resin. After N-alkylation of carbamimidothioate resin with ethyl 2-bromoac...

DURING A STUDY on the metabolism of histidine in a child affected with histidinemia (Beauvais, P., and Humbel, R., to be published), we became interested in the chromatography of imidazoles. In this disease the urine contains numerous imidazoles: histidine and its metabolites, imidazole-pyruvic, imidazole-lactic and imidazole-acetic acids and N-acetylhistidine.’I developed a chromatographic met...

Various tetrasubstituted pyrroles/pyrazoles have been prepared from nitro-substituted 1,3-enynes with aromatic amines/hydrazines via a copper-catalyzed cascade aza-Michael addition, cyclization and aromatization at room temperature. This protocol is also effective for the synthesis of tetrasubstituted pyrazoles in high yields.

A facile solid phase synthesis of 2,4,6,7-tetrasubstituted pyrrolo[2,3-d]pyrimidines is described. The synthesis involves a highly efficient five-step route starting from resin-bound dimeric peptoids. To demonstrate the versatility of our method, a representative library of 108 tetrasubstituted pyrrolo[2,3-d]pyrimidines of high quality was synthesized.

A series of tetrasubstituted aromatics has been synthesized, many of which are based on elaborated N-methyliminodiacetic acid (MIDA)-boronates. A sequence employing nitration, bromination, stepwise Suzuki-Miyaura (SM) coupling with a boronic acid, then base-mediated unmasking of the boronic acid from the MIDA-boronate and a second SM-coupling has led to our desired, mainly 1,2,4,5-substituted t...