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...
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| Veröffentlicht in: | Organic & biomolecular chemistry 2007-05, Vol.5 (10), p.1595 |
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| container_title | Organic & biomolecular chemistry |
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| creator | Keerthi, Kripa Gates, Kent S |
| description | 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. |
| doi_str_mv | 10.1039/b701179b |
| format | Article |
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| ispartof | Organic & biomolecular chemistry, 2007-05, Vol.5 (10), p.1595 |
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| language | eng |
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| source | MEDLINE; Royal Society of Chemistry Journals Archive (1841-2007); Royal Society Of Chemistry Journals 2008-; Alma/SFX Local Collection |
| subjects | Alkylating Agents - pharmacology Antibiotics, Antineoplastic - chemistry Benzoic Acid - chemistry Carboxylic Acids - chemistry Chemistry, Pharmaceutical - methods DNA - chemistry Fluorides - chemistry Hydrogen-Ion Concentration Ions Lactams - chemical synthesis Lactams - chemistry Macrolides - chemical synthesis Macrolides - chemistry Models, Chemical Sulfhydryl Compounds Sulfoxides - chemistry Thiazoles - chemical synthesis Thiazoles - chemistry Thiones - chemical synthesis Thiones - chemistry |
| title | Entering the leinamycin rearrangement via 2-(trimethylsilyl)ethyl sulfoxides |
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