Short Total Synthesis of Δ12-Prostaglandin J2 and Related Prostaglandins. Design, Synthesis, and Biological Evaluation of Macrocyclic Δ12-Prostaglandin J2 Analogues.
J Org Chem
; 84(1): 365-378, 2019 01 04.
Article
em En
| MEDLINE
| ID: mdl-30557504
ABSTRACT
Comprised of a large collection of structurally diverse molecules, the prostaglandins exhibit a wide range of biological properties. Among them are Δ12-prostaglandin J2 (Δ12-PGJ2) and Δ12-prostaglandin J3 (Δ12-PGJ3), whose unusual structural motifs and potent cytotoxicities present unique opportunities for chemical and biological investigations. Herein, we report a short olefin-metathesis-based total synthesis of Δ12-PGJ2 and its application to the construction of a series of designed analogues possessing monomeric, dimeric, trimeric, and tetrameric macrocyclic lactones consisting of units of this prostaglandin. Biological evaluation of these analogues led to interesting structure-activity relationships and trends and the discovery of a number of more potent antitumor agents than their parent naturally occurring molecules.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Desenho de Fármacos
/
Prostaglandina D2
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
J Org Chem
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos