Sparsomycin – a Review and Re-assessment

Abstract

The chemistry, biology, and biosynthesis of the microbial alkaloid sparsomycin (1) are summarized and re-assessed to identify future research initiatives for this biologically significant metabolite. INTRODUCTIONOne of the underexplored facets of natural product chemistry and biology is the further exploration of "old" bioactive metabolites to fill-in important gaps in basic knowledge, or to explore new or underappreciated applications given the contemporary opportunities in biological assessment and mechanistic understanding.The microbial alkaloid sparsomycin is one such example based on its anticancer, antimicrobial, insecticidal, and tRNA:mRNA translocation activities. Sparsomycin was first reported in 1962 by researchers at the Upjohn Co., Kalamazoo, MI, as a cytotoxic and antitumor alkaloid from the soil microorganism Streptomyces sparsogenes var. sparsogenes, 1,2 where it co-occurred with tubercidin. 2 Several years later, the molecular formula was corrected to C13H19N3O5S2 and the planar structure 1 determined through spectral interpretation and chemical degradation. 3,4 Additional isolations of 1 are rare. For example, a soil sample acquired in Kyoto, Japan, Streptomyces cuspidosporus was isolated and culturing yielded sparsomycin (1) and the antitubercular alkaloid tubercidin. 5 A water sample from the Nile River afforded 1 from Streptomyces violaceusniger AZ-NIOFD, 6 and a derivative of sparsomycin with a unit of H2O added was reported from a soil sample of Pseudomonas aeruginosa AZ-SH-B8 collected in the Sharqia Governorate in northern Egypt, 7 although the characterizations of these isolates were incomplete.Sparsomycin (1) has two stereocenters, the chiral carbon derived from an amino acid moiety and the S1sulfoxide unit. The earlier structural studies 2 had established the chiral carbon stereochemistry as

Total Syntheses of Sparsomycin and Sparoxomycins A1 and A2 via Sulfenate-Anion-Mediated Iterative C–S Bond Formation

“…Pyrimidinylpropenamides constitute a small class of antibiotics that exhibit a broad spectrum of biological activity, including anticancer, antibacterial, , antifungal, , and antiviral effects . Among these compounds, sparsomycin ( 1 ) was initially isolated from Streptomyces sparsogenes , and more recently, the related compounds sparoxomycins A 1 ( 2 ) and A 2 ( 3 ) were also isolated from the same source (Figure ).…”