RESUMO
The field of biomimetic synthesis seeks to apply biosynthetic hypotheses to the efficient construction of complex natural products. This approach can also guide the revision of incorrectly assigned structures. Herein, we describe the evolution of a concise total synthesis and structural reassignment of hyperelodione D, a tetracyclic meroterpenoid derived from a Hypericum plant, alongside some biogenetically related natural products, erectones A and B. The key step in the synthesis of hyperelodione D forms six stereocentres and three rings in a bioinspired cascade reaction that features an intermolecular Diels-Alder reaction, an intramolecular Prins reaction and a terminating cycloetherification.
Assuntos
Produtos Biológicos , Hypericum , Produtos Biológicos/química , Biomimética , Reação de CicloadiçãoRESUMO
The 2,6'-bijuglone natural product diospyrin and its unnatural 3,6'-isomer idospyrin have been synthesized in seven steps each from N,N-diethylsenecioamide in overall yields of 12% and 13%, respectively. The syntheses diverge from ramentaceone (7-methyljuglone) and include a key Suzuki-Miyaura cross-coupling. Diospyrin, idospyrin, and several synthetic precursors exhibit potent and selective cytotoxicity to the murine myeloma NS-1 cell line over neonatal foreskin cells.
Assuntos
Antineoplásicos/farmacologia , Antituberculosos/farmacologia , Naftoquinonas/química , Antineoplásicos/química , Antituberculosos/química , Isomerismo , Naftoquinonas/síntese química , Naftoquinonas/farmacologiaRESUMO
The first approaches to the 10'-anthronyl-2-anthraquinone skeleton have been devised, allowing two syntheses of the marine natural product albopunctatone. Both routes involve regioselective addition of a nucleophilic masked anthraquinone to a protected chrysazin derivative; the best affords albopunctatone in five steps and 35% overall yield. Albopunctatone exhibits potent inhibitory activity against Plasmodium falciparum and negligible toxicity to a range of other microbial pathogens and mammalian cells.
Assuntos
Antraquinonas/química , Antraquinonas/síntese química , Antimaláricos/química , Antimaláricos/síntese química , Urocordados/química , Animais , Antraquinonas/farmacologia , Antimaláricos/farmacologia , Linhagem Celular , Técnicas de Química Sintética , Humanos , Modelos Moleculares , Conformação Molecular , Plasmodium falciparum/efeitos dos fármacosRESUMO
1,5,7-Trihydroxy-6H-indeno[1,2-b]anthracene-6,11,13-trione (1), proposed to be the antitubercular natural product eucapsitrione, has been synthesized in 43% overall yield and six steps, including a key Suzuki-Miyaura biaryl coupling and a directed remote metalation (DReM)-initiated cyclization. The physical and spectroscopic properties of 1 do not match the data reported for the natural product. At this time there is insufficient information available to enable a structure reassignment. During the optimization of the Suzuki-Miyaura coupling, an unprecedented biaryl coupling ortho to the borono group was observed. The scope of this unusual reaction has been investigated.
