Zang H, Breydo L, Mitra K, Dannaldson J, Gates K S
Departments of Chemistry and Biochemistry, University of Missouri-Columbia, Columbia, MO 65211, USA.
Bioorg Med Chem Lett. 2001 Jun 18;11(12):1511-5. doi: 10.1016/s0960-894x(01)00196-2.
Previous work has shown that alkylation of DNA by the antitumor agent leinamycin (1) is potentiated by reaction of the antibiotic with thiols. Here, it is shown that other soft nucleophiles such as cyanide and phosphines can also trigger DNA alkylation by leinamycin. Overall, the results suggest that reactions of cyanide and phosphines with leinamycin produce the oxathiolanone intermediate (2), which is known to undergo rearrangement to the DNA-alkylating episulfonium ion 4.
先前的研究表明，抗肿瘤药物链黑菌素（1）对DNA的烷基化作用会因该抗生素与硫醇的反应而增强。在此研究中发现，其他软亲核试剂如氰化物和膦类也能引发链黑菌素对DNA的烷基化作用。总体而言，结果表明氰化物和膦类与链黑菌素的反应会生成氧杂硫杂环戊烷酮中间体（2），已知该中间体可重排为DNA烷基化的环硫鎓离子4。
