Kevin A. Sullivan

Novel, potent and selective cyclin D1/CDK4 inhibitors: indolo[6,7-a]pyrrolo[3,4-c]carbazoles.

The synthesis and CDK inhibitory properties of a series of indolo[6,7-a]pyrrolo[3,4-c]carbazoles is reported. In addition to their potent CDK activity, the compounds display antiproliferative activity against two human cancer cell lines. These inhibitors also effect strong G1 arrest in these cell lines and inhibit Rb phosphorylation at Ser780 consistent with inhibition of cyclin D1/CDK4.

5-Formyl salicylaldehyde as a linker for the synthesis of benzofuran containing insulin sensitivity enhancer compounds

Abstract 5-Formyl salicylaldehyde was prepared by treatment of 4-hydroxybenzaldehyde with HMTA in TFA. Reaction of this dialdehyde with α-haloacetyl aryl compounds gave 2,5-disubstituted benzofurans, from which an Insulin Sensitivity Enhancer compound was prepared.

Phenyliodine(III) bis(trifluoroacetate)-mediated oxidation of bisindolylmaleimides to indolo[2,3-a]carbazoles

A novel protocol for the oxidation of bisindolylmaleimides to the corresponding indolo[2,3-a]carbazoles in 15–56% yield with phenyliodine(III) bis(trifluoroacetate) (PIFA) is reported.

A novel, stereoselective synthesis of cis-4a (S), 8a(R)-decahydro-6(2H)-isoquinolones from meroquinene esters

Abstract Intramolecular cyclization of N-acylated meroquinene t-butyl esters in cold H2SO4 cleanly afforded cis-4a(S), 8a(R)-decahydro-6(2H)-isoquinolones with cmnplete stereocontrol in ⪢95% yield. Formation of the meroquinene esters from cinchona alkaloid autoxidation using an improved Doering protocol was accomplished in three steps with 85% overall yield.

Selective Monoarylation of Benzenediols via Dianion Intermediates

Abstract Application of the SNAr reaction on benzenediols with arylfluorides revealed an enhancement in monosubstitution selectivity over bis substitution when excess base was used. This trend was studied using symmetrical and nonsymmetrical benzenediols with various levels of steric hindrance. The effect of various bases was examined. A 100% monoselectivity was achieved in the presence of 2.5 equiv. of Cs2CO3. The methodology was employed in the synthesis of an important pharmaceutical product, 1, an arylether.