Robert W. DeSimone

Total synthesis of (+)- and (−)-norsecurinine

Abstract (−)-Norsecurinine ( 1a ) has been prepared in a stereospecific fashion beginning with the acetylenic oxazole 18 . Diels-Alder cyclization of 18 afforded the furanoketone 19 , which was transformed in five steps to the butenolide mesylate 24 . Transannular alkylation of 24 then afforded 1a . In identical fashion, ent- 18 gave (+)-norsecurinine ( 1b ).

Imidazo[1,2-a]pyrazine diaryl ureas: Inhibitors of the receptor tyrosine kinase EphB4

Inhibition of receptor tyrosine kinases (RTKs) such as vascular endothelial growth factor receptors (VEGFRs) and platelet-derived growth factor receptors (PDGFRs) has been validated by recently launched small molecules Sutent and Nexavar, both of which display activities against several angiogenesis-related RTKs. EphB4, a receptor tyrosine kinase (RTK) involved in the processes of embryogenesis and angiogenesis, has been shown to be aberrantly up regulated in many cancer types such as breast, lung, bladder and prostate. We propose that inhibition of EphB4 in addition to other validated RTKs would enhance the anti-angiogenic effect and ultimately result in more pronounced anti-cancer efficacy. Herein we report the discovery and SAR of a novel series of imidazo[1,2-a]pyrazine diarylureas that show nanomolar potency for the EphB4 receptor, in addition to potent activity against several other RTKs.

Tetrapyrroles. V. Formal syntheses of the ring-C,D pyrromethenones of phytochrome and phycocyanin

Abstract Formal syntheses of pyrromethenones 2 and 3 , potential intermediates for the preparation of phycocyanin ( 5 ) and phytochrome ( 4 ), respectively, have been accomplished by Pd o mediated coupling of iodopyrrole 7 with acetylenic amides of general structure 8a,b followed by F- catalyzed 5-exo-dig cyclization and DDQ oxidation.

Substituted 3-(2-benzoxazyl)-benzimidazol-2-(1H)-ones : A new class of GABAA brain receptor ligands

A novel class of potent benzodiazepine receptor (BZR) ligands has been designed and synthesized aided by molecular modeling of known benzodiazepine ligands such as CGS-8216 and the use of known pharmacophore models.