Lactimidomycin is a glutarimide antibiotic derived from the bacteria Streptomyces amphibiosporus.[1][2] It has antifungal, antiviral and anti-cancer properties, acting as a direct inhibitor of protein translation in ribosomes.[3][4][5] Antiviral activity is seen against a variety of RNA viruses including flaviviruses such as dengue fever, Kunjin virus and Modoc virus, as well as vesicular stomatitis virus and poliovirus.[6] As lactimidomycin is a natural product containing an unusual unsaturated 12-membered lactone ring, it has been the subject of numerous total synthesis approaches.[7][8][9][10]
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Formula | C26H35NO6 |
Molar mass | 457.567 g·mol−1 |
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References
edit- ^ Sugawara K, Nishiyama Y, Toda S, Komiyama N, Hatori M, Moriyama T, et al. (September 1992). "Lactimidomycin, a new glutarimide group antibiotic. Production, isolation, structure and biological activity". The Journal of Antibiotics. 45 (9): 1433–41. doi:10.7164/antibiotics.45.1433. PMID 1429229.
- ^ Ju J, Seo JW, Her Y, Lim SK, Shen B (December 2007). "New lactimidomycin congeners shed insight into lactimidomycin biosynthesis in Streptomyces amphibiosporus". Organic Letters. 9 (25): 5183–6. doi:10.1021/ol702249g. PMID 17997563.
- ^ Schneider-Poetsch T, Ju J, Eyler DE, Dang Y, Bhat S, Merrick WC, et al. (March 2010). "Inhibition of eukaryotic translation elongation by cycloheximide and lactimidomycin". Nature Chemical Biology. 6 (3): 209–217. doi:10.1038/nchembio.304. PMC 2831214. PMID 20118940.
- ^ Micoine K, Persich P, Llaveria J, Lam MH, Maderna A, Loganzo F, Fürstner A (June 2013). "Total syntheses and biological reassessment of lactimidomycin, isomigrastatin and congener glutarimide antibiotics". Chemistry: A European Journal. 19 (23): 7370–83. doi:10.1002/chem.201300393. PMID 23595541.
- ^ Garreau de Loubresse N, Prokhorova I, Holtkamp W, Rodnina MV, Yusupova G, Yusupov M (September 2014). "Structural basis for the inhibition of the eukaryotic ribosome". Nature. 513 (7519): 517–22. Bibcode:2014Natur.513..517G. doi:10.1038/nature13737. hdl:11858/00-001M-0000-0023-EE38-0. PMID 25209664. S2CID 4460881.
- ^ Carocci M, Yang PL (April 2016). "Lactimidomycin is a broad-spectrum inhibitor of dengue and other RNA viruses". Antiviral Research. 128: 57–62. doi:10.1016/j.antiviral.2016.02.005. PMC 4850914. PMID 26872864.
- ^ Micoine K, Fürstner A (October 2010). "Concise total synthesis of the potent translation and cell migration inhibitor lactimidomycin". Journal of the American Chemical Society. 132 (40): 14064–6. doi:10.1021/ja107141p. PMID 20831202.
- ^ Larsen BJ, Sun Z, Nagorny P (June 2013). "Synthesis of eukaryotic translation elongation inhibitor lactimidomycin via Zn(II)-mediated Horner-Wadsworth-Emmons macrocyclization". Organic Letters. 15 (12): 2998–3001. doi:10.1021/ol401186f. PMID 23731327.
- ^ Nagasawa T, Kuwahara S (June 2013). "Formal total synthesis of lactimidomycin". Organic Letters. 15 (12): 3002–5. doi:10.1021/ol401214f. PMID 23731346.
- ^ Larsen BJ, Sun Z, Lachacz E, Khomutnyk Y, Soellner MB, Nagorny P (December 2015). "Synthesis and Biological Evaluation of Lactimidomycin and Its Analogues". Chemistry: A European Journal. 21 (52): 19159–67. doi:10.1002/chem.201503527. PMID 26577990.