Total synthesis and antiviral activity of indolosesquiterpenoids from the xiamycin and oridamycin families.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 25648883.
- Also identified by DOI 10.1038/ncomms7096 and PMC identifier 4347019.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Indolosesquiterpenoids are a growing class of natural products that exhibit a wide range of biological activities. Here, we report the total syntheses of xiamycin A and oridamycins A and B, indolosesquiterpenoids isolated from Streptomyces. Two parallel strategies were exploited to forge the carbazole core: 6π-electrocyclization/aromatization and indole C2-H bond activation/Heck annulation. The construction of their trans-decalin motifs relied on two diastereochemically complementary radical cyclization reactions mediated by Ti(III) and Mn(III), respectively. The C23 hydroxyl of oridamycin B was introduced by an sp(3) C-H bond oxidation at a late stage. On the basis of the chemistry developed, the dimeric congener dixiamycin C has been synthesized for the first time. Evaluation of the antiviral activity of these compounds revealed that xiamycin A is a potent agent against herpes simplex virus-1 (HSV-1) in vitro.
Medical subject headings
- Antiviral Agents
- Sesquiterpenes