RESUMO
An approach to aberrarone, an antimalarial diterpenoid natural product with tetracyclic skeleton is reported. Key to the stereoselective preparation of the 6-5-5 tricyclic skeleton includes the mediation of Nagata reagent for constructing the C1 all-carbon quaternary centers and gold-catalyzed cyclopentenone synthesis through C-H insertion.
RESUMO
Two complex norditerpenoids, caribenols A and B, were accessed from a common building block. Our synthesis of caribenol A features the diastereoselective formation of the seven-membered ring through a Friedel-Crafts triflation and a late-stage oxidation of a furan ring. The first synthesis of caribenol B was achieved using an intramolecular organocatalytic α-arylation. An unusual intramolecular aldol addition was developed for the assembly of its cyclopentenone moiety, and the challenging trans-diol moiety was installed through a selective nucleophilic addition to a hydroxy 1,2-diketone. Our overall synthetic strategy, which also resulted in a second-generation synthesis of amphilectolide, confirms the usefulness of furans as powerful nucleophiles and versatile synthons.
Assuntos
Diterpenos/síntese química , Furanos/química , Diterpenos/química , Conformação MolecularRESUMO
The first asymmetric synthesis of a scillascillin-type homoisoflavonoid was reported. Key reactions for the asymmetric synthesis of benzocyclobutene include catalytic reductive desymmetrization of malonic ester and an intramolecular C-H activation of the methyl group.
RESUMO
Perhydrolysis of a sterically congested multifunctional epoxide was achieved in ethereal H2O2 with the aid of a recently developed Mo catalyst. The resulting hydroperoxide cyclized to give a 1,2,4-trioxane, which could be readily elaborated into qinghaosu and a range of novel analogues. Some of the compounds with two such trioxane moieties showed in vitro antimalarial activity comparable to or even better than that of artesunate or chloroquine.
Assuntos
Antimaláricos/química , Artemisininas/química , Compostos de Epóxi/química , Compostos Heterocíclicos/química , Compostos Heterocíclicos/farmacologia , Peróxido de Hidrogênio/química , Antimaláricos/farmacologia , Artesunato , CiclizaçãoRESUMO
An intramolecular formal [3 + 2] cationic cycloaddition between benzylic carbocation and styrene was developed for the total synthesis of codonopiloneolignanin A. Further study shows benzocycloheptene as a good substrate for 1,3-dipolar cycloaddition, and a model study toward cephalocyclidine A skeleton was reported.
Assuntos
Lignanas/síntese química , Catálise , Reação de Cicloadição , Lignanas/química , Estrutura Molecular , EstereoisomerismoRESUMO
A convenient approach to the construction of the 5-6-7 tricarbocyclic fused core structure of cyanthiwigins via a Co-mediated Pauson-Khand reaction as a key step has been developed. The cyathane core intermediate obtained by this strategy was used in the concise synthesis of (±)-5- epi-cyanthiwigin I. The developed chemistry paves the way for the total synthesis of structurally diverse cyanthiwigins.
RESUMO
A series of 1,2,4-trioxanes were synthesized in which the key peroxy bonds were installed through a molybdenum-catalyzed perhydrolysis of the epoxy rings. A core structure was identified that may serve as a promising lead structure for further investigations because of its high antimalarial activity (comparable to that of artesunate and chloroquine), apparent potential for scale-up and derivatization, and facile monitoring/tracing by using UV light.
Assuntos
Antimaláricos/química , Artemisininas/química , Antimaláricos/síntese química , Artemisininas/síntese química , Catálise , Ciclização , Compostos de Epóxi/química , Compostos Heterocíclicos/química , Molibdênio/química , Relação Estrutura-Atividade , Raios UltravioletaRESUMO
Attachment of H(2)O(2) onto the highly hindered quaternary C-12a in an advanced qinghaosu (artemisinin) precursor has been achieved through a facile perhydrolysis of a spiro epoxy ring with the aid of a previously unknown molybdenum species without involving any special equipment or complicated operations. The resultant ß-hydroxyhydroperoxide can be further elaborated into qinghaosu, illustrating an entry fundamentally different from the existing ones to this outstanding natural product of great importance in malaria chemotherapy.
Assuntos
Artemisininas/química , Peróxido de Hidrogênio/química , Compostos de Epóxi/química , Estrutura MolecularRESUMO
At ambient temperature, in the presence of catalytic amounts of phosphomolybdic acid (PMA), ethereal hydrogen peroxide reacted readily with a range of epoxides, giving corresponding beta-hydroxyhydroperoxides in high yields.
Assuntos
Óxido de Etileno/química , Peróxido de Hidrogênio/química , Molibdênio/química , Ácidos Fosfóricos/química , Catálise , Ciclização , Estrutura Molecular , EstereoisomerismoRESUMO
Ketones or ketals were readily converted into the corresponding gem-dihydroperoxides in high yields by treatment with ethereal H(2)O(2) at ambient temperature in the presence of 2-5 mol % of phosphomolybdic acid.