RESUMO
PNU-95666E is being developed for the treatment of Parkinson's disease. This review will describe the syntheses of this D2 agonist proceeding from the very early routes to a usable production route.
RESUMO
The semisynthesis of Taxol was critical to its development as a drug. This review focuses on methods that have been developed to convert the readily available 10-deacetylbaccatin III (10-DAB) into Taxol, highlighting the various protection schemes used for the phenylisoserine side chain and 10-DAB, along with the methods developed for the conjoining of the side chain to the hindered C-13 hydroxyl of the diterpenoid framework.
RESUMO
Two stereoselective syntheses of a new pseudodipeptide isostere, the right-hand hydroxyethylene dipeptidomimetic (Xaa psi[CH2CH(OH)]Yaa), are presented. In one method readily available amino acids are used as starting materials for Evans chiral aldol condensation chemistry. The second method relies on the synthesis of an anti-aldol product for the hydroxyethylene isostere via an E-selective ethyl hydrocinnamate enolization, and thus allows for the synthesis of isosteres having side chains other than those available from amino acids. Both methods are illustrated by the chiral synthesis of Boc-Phe psi[CH2CH(OH)]Phe. Two diastereomers, (S,S,R) and (S,R,R), are incorporated into an HIV-1 protease inhibitor template which yields potent inhibitors of HIV-1 protease when the pseudodipeptide isostere is Phe psi[CH(OH)CH2]Phe or Phe psi[CH(OH)CH(OH)]Phe. The resulting Phe psi[CH2CH(OH)]Phe-containing inhibitors possess modest potency.
Assuntos
Dipeptídeos/química , Inibidores da Protease de HIV/química , HIV-1 , Desenho de Fármacos , Modelos Químicos , Estrutura Molecular , EstereoisomerismoRESUMO
A new type of pseudopeptide isostere exampled by Phe psi[CH2CH(OH)]Phe was synthesized from phenylalanine. The HIV protease inhibitory activity (IC50) of Noa-His-Phe psi[CH2CH(OH)]Phe-Ile-Amp was 0.8 pmol.L-1.
