Structure-activity studies of irumamycin type macrolides from Streptomyces sp. INA-Ac-5812

• Published in: Tetrahedron letters 2019-05, Vol.60 (21), p.1448-1451
• Main Authors: Alferova, Vera A., Shuvalov, Maxim V., Novikov, Roman A., Trenin, Alexey S., Dezhenkova, Lubov G., Gladkikh, Elena G., Lapchinskaya, Olda A., Kulyaeva, Valeriya V., Bychkova, Olga P., Mirchink, Elena P., Solyev, Pavel N., Kudryakova, Gulnara Kh, Korshun, Vladimir A., Tyurin, Anton P.
• Format: Article
• Language: English
• Subjects: Antifungal activity; Irumamycin; Macrolide antibiotics; Streptomyces sp. INA-Ac-5812
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2019.04.051

[Display omitted] •3 macrolides, known irumamycin and X-14952B, and new isoirumamycin were isolated.•Unknown stereo configurations of irumamycin C3, C7, C23, C24 were deduced by NMR.•The crucial importance of 20-membered ring for antifungal properties was shown. Three natural glycosylated macrolide compounds, known irumamycin 1 and X-14952B 2, as well as new isoirumamycin 3, were isolated from ethyl acetate mycelium extract of Streptomyces sp. INA-Ac-5812. Structures of the compounds were elucidated using 1D and 2D NMR. Isoirumamycin 3 was found to be an isomer of irumamycin with an 18-membered macrolactone ring instead of 20-membered macrolide in irumamycin. A previously unknown stereo configuration of irumamycin epoxide (C23, C24) and hemiketal (C3, C7) fragments was deduced from NMR data (ROESY/NOESY and HSQMBC). Cytotoxic, antifungal and antibacterial activities were studied for all isolated compounds. Comparison of the collected data showed crucial importance of 20-membered macrolactone ring for antimicrobial properties of this antibiotic family.