RESUMO
A different approach to the synthesis of dipeptides is described based on the formation of the NHCHR1CONH-CHR2CO bond by carbenoid N-H insertion, rather than the formation of the peptide bond itself. Thus decomposition of triethyl diazophosphonoacetate catalysed by rhodium(II) acetate in the presence of N-protected amino acid amides 8 gives the phosphonates 9. Subsequent Wadsworth-Emmons reaction of 9 with aldehydes in the presence of DBU gives dehydro dipeptides 10. The reaction has been extended to a simple two-step procedure, without the isolation of the intermediate phosphonate, for conversion of a range of amino acid amides 11 into dehydro dipeptides 12 and to an N-methylamide 11 h, and for conversion of a dipeptide to tripeptide (13-->14). Direct conversion, by using methyl diazophenylacetate, of amino acid amides to phenylglycine-containing dipeptides 19 proceeds in good chemical yield, but with poor diastereoselectivity.
Assuntos
Amidas/química , Biossíntese Peptídica , Aminoácidos/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas/métodos , Espectrofotometria InfravermelhoRESUMO
The synthesis and in vitro evaluation of the acetamidine derivatives of hetero-substituted lysine and homolysine analogues have identified potent inhibitors of human nitric oxide synthase enzymes, including examples with marked selectivity for the inducible isoform.
Assuntos
Acetamidas/síntese química , Inibidores Enzimáticos/síntese química , Lisina/análogos & derivados , Lisina/síntese química , Óxido Nítrico Sintase/antagonistas & inibidores , Acetamidas/farmacologia , Inibidores Enzimáticos/farmacologia , Humanos , Indicadores e Reagentes , Isoenzimas/antagonistas & inibidores , Lisina/farmacologia , Óxido Nítrico Sintase Tipo II , Ornitina/análogos & derivados , Ornitina/farmacologia , Sulfetos/farmacologia , Sulfonas/farmacologiaRESUMO
The current interest in solid-phase organic synthesis has led to a renewed interest in a complementary technique in which solid supported reagents are used in solution phase chemistry. This technique obviates the need for attachment of the substrate to a solid-support, and enables the chemist to monitor the reactions using familiar analytical techniques. The purpose of this review is to increase awareness of the wide range of useful transformations which can be accomplished using solid-supported reagents.
Assuntos
Química Farmacêutica , Catálise , Oxirredução , PolímerosRESUMO
The use of solution phase techniques has been explored as an alternative to solid-phase chemistry approaches for the preparation of arrays of compounds in the drug discovery process. Solution-phase work is free from some of the constraints of solid-phase approaches but has disadvantages with respect to purification. This article will also illustrate some of the advances made in recent years in solution phase array chemistry including using supported reagents and simple extractive protocols for the effective preparation of high quality samples.