Sintese total e elucidação estrutural da delactomicina

AUTOR(ES)
DATA DE PUBLICAÇÃO

2003

RESUMO

The natural polyketide delactonmycin isolated from Streptomyces strains displays potent inhibitory activity of the nucleo-cytoplasmic translocation of the HIV -1 regulatory protein Rev. The planar structure of delactonmycin was established by spectroscopic methods, but its relative as well as its absolute configuration remained unknown. In this work, we describe the first total synthesis and structural elucidation of delactonmycin The synthetic approach to delactonmycin featured some key points to save the integrity of the b,g-unsaturated ketone, appropriately control configuration of the double bonds and the absolute stereochemistry of stereogenic centers, without compromise the synthetic route efficiency. The pivotal steps on the preparation of delactonmycin framework were: a palladium(0)-catalysed Negishi coupling reaction for the construction of C11-C 16 subunit; a diastereoselective tin-mediated syn-selective aldol reaction for assembling the subunits C7-ClO and C11-C16; and a Wittig olefination for the installation of the conjugated (E,E)-diene C5-C6 and C6-C7. The spectroscopic data of the synthetic (- )-delactonmycin nicely matched those reported for the natural product, allowing us to confirm their identity and unambiguously establish its configuration. Unfortunately, the lack of a sample of natural de1actonmycin or of its chiroptical data precluded the determination of its absolute configuration

ASSUNTO(S)

agentes antivirais produtos naturais streptomyces

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