New potentiators of amphotericin B activity, shodoamides A to C produced by Pseudophialophora sp. BF-0158
Yagi A, Kashima M., Ishijima H., Tomoda H., Uchida, R.
J Antibiot, 2023／Accepted: 20 June 2023
During our screening program for new potentiators of amphotericin B activity against Candida albicans, shodoamides A to C (1–3) were isolated from a culture broth of the fungus Pseudophialophora sp. BF-0158 fermented under shaking conditions. A known congener named shodoamide D (4) in this paper was obtained from a culture broth of the BF-0158 strain fermented under static conditions. The structures of 1–4 were assigned based on spectroscopic analyses, including NMR and MS, and were found to have a common N-(2´,3´,4´-trihydroxybutyl)-6-methyl-2,4-tetradecadienamide structure. Compounds 1–3 exhibited no antifungal activity, but they induced up to 32-fold increases in amphotericin B activity against C. albicans by a microdilution method.
Total synthesis of tanzawaic acid A
Tanaka K., Suzuki S., Lee D., Arima S., Ohte S. Ohshiro T., Uchida R., Tomoda H., Nagamitsu T.
Tetrahedron, 2023, 143: 133556／Accepted: 23 July 2023
The total synthesis of tanzawaic acid A, a potent antifungal active against Rhizopus oryzae, has been achieved. Key features of the synthetic strategy include the Heck reaction between a sterically hindered triflate and methyl acrylate and Evans alkylation/Friedel–Crafts acylation/stereoselective hydrogenation for the stereoselective construction of the triflate with a tetrahydronaphthalene unit. The practical total synthesis provided tanzawaic acid A with an overall yield of 29% over 20 steps.
New piericidin rhamnosides as potentiators of amphotericin B activity against Candida albicans produced by actinomycete strain TMPU-A0287
Yagi A, Yamaguchi Y, Kawasaki K, Usui E, Yamazaki H, Uchida, R.
J Antibiot, 2023, 76: 65–74／Accepted: 11 November 2022
Four new piericidin rhamnosides (2, 4–6) together with three known piericidins (1, 3, 7) were isolated from the culture broth of the unidentified actinomycete strain TMPU-A0287 as potentiators of antifungal amphotericin B (AmB) activity. The structures of piericidins were elucidated by spectroscopic analyses, including NMR and MS. Compounds 2 and 4–6 possessed a ketone at C-10 and one or two methoxy groups on the rhamnose in their structures. Compounds 1–7 did not exhibit antifungal activity against Candida albicans and all potentiated AmB activity. The MIC values of AmB against C. albicans combined with 1–7 (4.0 µg/ml) decreased from 0.50 to 0.063 or 0.031 µg/ml, yielding an 8- or 16-fold increase in AmB activity.
日本薬学会第143年会，札幌，令和 5 年 3 月
Streptomyces sp. TMPU-20A065 株が生産する新規 liposidomycin 類の抗 Mycobacterium avium complex 活性
八木 瑛穂、冨士原 万柚、内田 龍児
植野 あゆみ、李 大葵、有馬 志保、大城 太一、内田 龍児、供田 洋、長光 亨
鎌塚 早紀、李 大葵、内田 龍児、長光 亨
Shodoamide C の全合成研究
平田 晃大、岩堀 雅大、大城 太一、供田 洋、内田 龍児、長光 亨、大多和 正樹