ATP Depletion Assay Led to the Isolation of New 36-Membered Polyol Macrolides Deplelides A and B from Streptomyces sp. MM581-NF15

• Published in: Organic letters 2017-08, Vol.19 (16), p.4207-4210
• Main Authors: Takeuchi, Toshifumi, Hatano, Masaki, Umekita, Maya, Hayashi, Chigusa, Wada, Shun-ichi, Nagayoshi, Miho, Sawa, Ryuichi, Kubota, Yumiko, Kawada, Manabu, Igarashi, Masayuki, Shibasaki, Masakatsu
• Format: Article
• Language: English
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/acs.orglett.7b01807

New 36-membered polyol macrolides deplelides A and B were isolated from the culture of Streptomyces MM581-NF15 by bioassay-guided fractionation using an ATP depletion assay. The planar structures of these novel compounds were identified by interpretation of the spectroscopic data (1D/2D NMR, MS, and IR). The relative stereochemistry was partially established using the universal NMR database method and J-based configuration analysis using 1H–1H and long-range 1H–13C coupling constants determined by 1H NMR or E.COSY and J-resolved HMBC analysis or another HMBC-based technique, respectively. The absolute stereochemistry was partially determined by a modified Mosher’s method. These new compounds displayed highly potent ATP depletion activities (IC50 33 nM) and antiproliferative activities against several tumor cell lines, such as HGC-27 (IC50 47 nM).