RESUMO
[reaction: see text] A nine-step, stereoselective synthesis of bipinnatin J is described, which features a ruthenium-catalyzed Alder-ene reaction, a Stille cross coupling, and an intramolecular Nozaki-Hiyama-Kishi allylation as key steps. The biosynthetic relationship between bipinnatin J and complex polycyclic diterpenes isolated from gorgonian corals is discussed.
Assuntos
Diterpenos/síntese química , Animais , Antozoários/química , Catálise , Diterpenos/química , Estrutura Molecular , EstereoisomerismoRESUMO
The asymmetric total synthesis of (-)-bipinnatin J and its conversion into (+)-intricarene through a transannular 1,3-dipolar cycloaddition is described. In addition, the conversion of (-)-bipinnatin J into (+)-rubifolide and (+)-isoepilophodione B is reported. Biosynthetic relationships among furanocembranoids and the possible role of 1,3-dipolar cycloadditions in biosynthesis are discussed. [reaction: see text]
Assuntos
Diterpenos/síntese química , Triterpenos/síntese química , Ciclização , Diterpenos/química , Espectroscopia de Ressonância Magnética , Oxirredução , EstereoisomerismoRESUMO
[reaction: see text] Synthesis of the northern hemisphere (C1-C16) of bryostatin 1, a potent anticancer agent, has been accomplished in 14 steps and 11% overall yield via desymmetrization by ketalization/ring-closing metathesis. A 2,9-dioxabicyclo[3.3.1]nonane template facilitated stereoselective A-ring functionalization, while an efficient hetero-Diels-Alder reaction was used to elaborate the B-ring.
Assuntos
Acetais/química , Antineoplásicos/síntese química , Macrolídeos/síntese química , Alcanos/química , Compostos Bicíclicos com Pontes/química , Briostatinas , Ciclização , Estrutura MolecularRESUMO
Pteridinone-based Toll-like receptor 7 (TLR7) agonists were identified as potent and selective alternatives to the previously reported adenine-based agonists, leading to the discovery of GS-9620. Analogues were optimized for the immunomodulatory activity and selectivity versus other TLRs, based on differential induction of key cytokines including interferon α (IFN-α) and tumor necrosis factor α (TNF-α). In addition, physicochemical properties were adjusted to achieve desirable in vivo pharmacokinetic and pharmacodynamic properties. GS-9620 is currently in clinical evaluation for the treatment of chronic hepatitis B (HBV) infection.
Assuntos
Antivirais/farmacologia , Hepatite B Crônica/tratamento farmacológico , Pteridinas/farmacologia , Receptor 7 Toll-Like/agonistas , Administração Oral , Animais , Antivirais/química , Antivirais/metabolismo , Antivirais/farmacocinética , Cães , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Masculino , Camundongos , Microssomos Hepáticos/metabolismo , Modelos Moleculares , Conformação Proteica , Pteridinas/química , Pteridinas/metabolismo , Pteridinas/farmacocinética , Ratos , Relação Estrutura-Atividade , Especificidade por Substrato , Receptor 7 Toll-Like/química , Receptor 7 Toll-Like/metabolismoRESUMO
An overview of the chemistry and biology of the diterpene natural products known as the furanocembranoids, pseudopteranes, and gersolanes is provided; 85 references are cited.
Assuntos
Produtos Biológicos/química , Produtos Biológicos/farmacologia , Diterpenos/química , Diterpenos/farmacologia , Biologia Marinha , Mimetismo Molecular , Estrutura MolecularRESUMO
An efficient synthesis of Hale and co-workers' C17-C27 bryostatin southern hemisphere intermediate has been accomplished in six steps and 33% overall yield from (R)-2-(benzyloxy)propanal. The synthesis features a one-pot DIBALH/HWE ester homologation as well as a novel acetonide rearrangement/glycal formation cascade.