Synthesis of new purine derivatives for SAR studies on Mycobacterium tuberculosis

Abstract

O diaminomaleonitrilo, um reagente disponível comercialmente, foi tratado com trietilortoformiato para gerar o (Z)-N-(2-amino-1,2-dicianovinil)formimidato de etilo. O último composto fez-se reagir com as aminas primárias para gerar as (Z)-N-(2-amino-1,2- dicianovinil) formamidinas, que na presença de base ciclizam intramolecularmente formando as 5-amino-4-(cianoformimidoil)imidazoles. 6-Cianopurinas foram obtidas por reacção das (Z)-N-(2-amino-1,2-dicianovinil) formamidinas e dos 5-amino-4-(cianoformimidoil) imidazoles com trietilortoformiato. As 6-cianopurinas foram usadas como reagente de partida para gerar 6-imidatopurinas, por reacção com o ião metoxido, e as 6-(N´-hydroxy)carboximidamidopurinas, por reacção com hidroxilamina. Os últimos compostos foram tratados com derivados de ácido carboxílico para gerar as 6- carboximidamidopurinas. As 6-imidatopurinas reagiram com O-benzilhidroxilamina e derivados de hidrazida tendo dado origem às 6-(N´-benzoyloxy)carboximidamidopurinas e às 6- carbohidrazonamidopurinas, respectivamente. As 6-carbohidrazonamidopurinas foram usadas como reagentes de partida para gerar as novas pyrimido[5,4-d]pyrimidinas por reacção com um nucleófilo e estes últimos compostos foram convertidos nas 6-triazolopurinas por aquecimento na presenҫa de catálise acidíca.

Diaminomaleonitrile, a commercially available reagent, was treated with triethylorthoformiate to generate ethyl (Z)-N-(2-amino-1,2-dicyanovinil)formimidate. The latter compound was reacted with selected primary amines to generate (Z)-N-(2-amino-1,2- dicyanovinil)formamidines, that in the presence of base evolved to 5-amino-4- (cyanoformimidoyl)imidazoles. The 6-cyanopurines were obtained from both the two last compounds by reaction with triethylorthoformiate. The 6-cyanopurines were used as starting materials to generate 6-imidatopurines, by reaction with methoxide ion, and 6-(N´-hydroxy)carboximidamidepurines by reaction with hydroxylamine. The latter compounds reacted with acid derivatives generating 6- carboximidamidepurines. The 6-imidatopurines were reacted with O-benzylhydroxylamine and hydrazide derivatives generating 6-(N´-benzoyloxy)carboximidamidepurines and 6- carbohydrazonamidepurines, respectively. The 6-carbohydrazonamidepurines were used as starting material to generate new pyrimido[5,4-d]pyrimidines by reaction with a nucleophile and the latter compounds were converted to 6-triazolopurines by heating in the presence of acid catalysis.