RESUMO
Ring contraction of 2,5-diketopiperazines by TRAL-alkylation led us to the stereoselective synthesis of original pyrrolidine-2,4-diones, a novel series of promising molecules with moderate anti-proliferative activity on breast cancer cells.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Dicetopiperazinas/química , Pirrolidinas/química , Pirrolidinas/farmacologia , Alquilação , Antineoplásicos/síntese química , Proliferação de Células/efeitos dos fármacos , Dicetopiperazinas/síntese química , Feminino , Humanos , Pirrolidinas/síntese química , EstereoisomerismoRESUMO
The electrophilic reactivity of Boc-DKPs has been studied. Thanks to Boc activation, the opening ability of carbonyl lactam groups is enhanced. According to experimental conditions, this enabled the synthesis of Boc-amino acid derivatives or original dipeptides via a regioselective and sequential way.
Assuntos
Dicetopiperazinas/química , Aminoácidos/síntese química , Aminoácidos/química , Dipeptídeos/síntese química , Dipeptídeos/química , Estrutura Molecular , EstereoisomerismoRESUMO
An efficient and original stereocontrolled transannular rearrangement starting from activated 2,5-diketopiperazines has been developed, an opportunity for the medicinal chemistry field, which requests access to novel biological scaffolds. This powerful ring contraction, which can be related to a stereoselective aza-version of the Chan rearrangement, allows for example the one-step synthesis of various tetramic acids, access to 2-disubstituted statins, or the synthesis of relevant lactam-constrained dipeptide mimetics using a TRAL-RCM sequence.
Assuntos
Piperazinas/química , Alquilação , Materiais Biomiméticos/síntese química , Dipeptídeos/síntese química , Lactamas/química , Estereoisomerismo , Especificidade por SubstratoRESUMO
Chiral 3-aminopyrrolidine-2,4-diones, obtained by transannular rearrangement of activated diketopiperazines, could be a springboard toward an exceptional stereoselective synthesis of original 2-disubstituted statines. After a selective reduction of the pyrrolidine-2,4-diones, the access to opened 2,4-diamino-3-hydroxyacid esters was carried out by a subsequent alkaline treatment or directly through a tandem reduction-solvolysis.
Assuntos
Aminoácidos/química , Dicetopiperazinas/química , Hidroxiácidos/síntese química , Aminação , Aminoácidos/síntese química , Cristalografia por Raios X , Hidroxiácidos/química , Lactamas/química , Modelos Moleculares , Estrutura Molecular , Oxirredução , Pirrolidinas/química , EstereoisomerismoRESUMO
A novel solid-phase strategy allows the efficient preparation of "traceless" sulfahydantoins. A total of 28 derivatives, with crude purity generally higher than 85%, were prepared by parallel synthesis. Through reductive alkylations, Mitsunobu reactions, and sulfamoylation reactions on oxime resin, the synthetic strategy affords sulfahydantoin derivatives selectively substituted at N(2), N(5) and N(2), N(5) positions, although yields of disubstituted compounds are lower. The mild reaction conditions involved lead to sulfahydantoins without racemization.
