Intramolecular Diels-Alder chemistry of 4-vinylimidazoles
An investigation of 4-vinylimidazoles as diene components in the intramolecular Diels-Alder reaction is described. In the course of these studies several parameters affecting the cycloaddition were evaluated including the nature of the imidazole protecting group, the type of dienophile and the linking group. These investigations established that amino linkers were generally more effective than either ethers or esters. In most cases, the cycloadditions were highly stereoselective, resulting in the formation of products derived from an anti transition state. The polysubstituted tetrahydrobenzimidazole core of the pyrrole-imidazole alkaloid ageliferin can be constructed through the use of pseudo dimeric 4-vinylimidazoles.
He, Yong,Krishnamoorthy, Pasupathy,Lima, Heather M.,Chen, Yingzhong,Wu, Haiyan,Sivappa, Rasapalli,Dias, H. V. Rasika,Lovely, Carl J.
p. 2685 - 2701
(2011/05/08)
Synthesis and evaluation of potent, highly-selective, 3-aryl-piperazinone inhibitors of protein geranylgeranyltransferase-I
A series of compounds based on the carboxyl-terminal CAAL sequence of PGGTase-I substrates was designed and synthesized. Using piperazin-2-one as a semi-rigid scaffold, we have introduced critical pharmacophores in a well-defined arrangement to mimic the CAAL sequence. High potency and exceptional selectivity were obtained for inhibition of PGGTase-I with structures such as 45 and 70. Potency of this series of GGTIs was dependent on the presence of an l-leucine residue with a free carboxyl terminus, as well as an S configuration of the 3-aryl group. The selectivity was significantly enhanced by 5-methyl substitution on the imidazole ring and fluorine substitution on the 3-aryl group. Modification of the 6-position of the piperazinone scaffold was found to be unfavorable. Compounds 44 and 69, the corresponding methyl esters of 45 and 70, were found to selectively block processing of Rap1A by PGGTase-I in whole cells with IC50 values of 0.4 M and 0.7 M respectively. The Royal Society of Chemistry 2006.
Peng, Hairuo,Carrico, Dora,Thai, Van,Blaskovich, Michelle,Bucher, Cynthia,Pusateri, Erin E.,Sebti, Said M.,Hamilton, Andrew D.
p. 1768 - 1784
(2008/02/05)
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