Entering the leinamycin rearrangement via 2-(trimethylsilyl)ethyl sulfoxides.
Attack of cellular thiols on the antitumor natural product leinamycin is believed to generate a sulfenate intermediate that undergoes subsequent rearrangement to a DNA-alkylating episulfonium ion. Here, 2-(trimethylsilyl)ethyl sulfoxides were employed in a fluoride-triggered generation of sulfenate anions related to the putative leinamycin-sulfenate. The resulting sulfenates enter smoothly into a leinamycin-type rearrangement reaction to afford an episulfonium ion alkylating agent. The results provide evidence that the sulfenate ion is, indeed, a competent intermediate in the leinamycin rearrangement. Further, the molecules examined here may provide a foundation for the design of functional leinamycin analogues that bypass the unstable and synthetically challenging 1,2-dithiolan-3-one 1-oxide moiety found in the natural product.
Keerthi
Kripa
K
Department of Chemistry and Biochemistry, University of Missouri-Columbia, Columbia, MO 65211, USA.
Gates
Kent S
KS
D000477:Alkylating Agents / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000737:chemistry; D019817:Benzoic Acid / Q000737:chemistry; D002264:Carboxylic Acids / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004247:DNA / Q000737:chemistry*; D005459:Fluorides / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007477:Ions; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry*; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry*; D008956:Models, Chemical; D013438:Sulfhydryl Compounds; D013454:Sulfoxides / Q000737:chemistry*; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry*; D013871:Thiones / Q000138:chemical synthesis* / Q000737:chemistry*
D000477:Alkylating Agents; D000903:Antibiotics, Antineoplastic; D002264:Carboxylic Acids; D007477:Ions; D007769:Lactams; D018942:Macrolides; D013438:Sulfhydryl Compounds; D013454:Sulfoxides; D013844:Thiazoles; D013871:Thiones; C059000:leinamycin; D019817:Benzoic Acid; D004247:DNA; D005459:Fluorides