Rodriguez RA, Steed DB, Kawamata Y, Su S, Smith PA, Steed TC, Romesberg FE, * Baran
PS. * The Scripps Research Institute, La Jolla, RQx Pharmaceuticals, La Jolla, and
University of California, San Diego, USA
Axinellamines as Broad-Spectrum Antibacterial Agents: Scalable Synthesis and Biology.
J. Am. Chem. Soc. 2014;
136: 15403-15413
Key words
axinellamines - antibiotics - Pauson–Khand reaction - chlorospirocyclization
Significance
Pyrrole–imidazole alkaloids are a class of complex natural products with intriguing
biological activities, isolated from marine sponges. The authors present a full account
of their synthetic efforts to derive substantial quantities of racemic axinellamines
A and B. In addition, valuable follow-up biological studies showing antibiotic activity
against Gram-positive and -negative bacteria are presented.
Comment
The authors disclose details of recent work directed towards the efficient synthesis
of axinellamines A and B (J. Am. Chem. Soc.
2011, 133, 13922). A Pauson–Khand reaction afforded cyclopentene C, which could be efficiently converted into diazide G. Oxidative cyclization, deprotection, and imidazole formation followed by a dihydroxylation–dehydration
sequence led to J. Silver(II)-mediated oxidation, azide reduction, and amidation afforded the two targets.
