Comprehensive semisyntheses of catathelasmols C, D, and E from D-glutamic acid, utilizing lipase-catalyzed site-selective reactions on intermediates

• Published in: Bioscience, Biotechnology, and Biochemistry
• Main Authors: Hashiba, Rinta, Hashimoto, Riichi, Nishiguchi, Momoko, Kobayashi, Toshifumi, Hanaya, Kengo, Higashibayashi, Shuhei, Sugai, Takeshi
• Format: Article in Journal/Newspaper
• Language: English
• Published: Oxford University Press (OUP) 2020
• Subjects: Organic Chemistry; Molecular Biology; Applied Microbiology and Biotechnology; General Medicine; Biochemistry; Analytical Chemistry; Biotechnology; Antarc*; Antarctica
• Online Access: http://dx.doi.org/10.1080/09168451.2020.1754159; http://academic.oup.com/bbb/article-pdf/84/7/1339/36826684/bbb1339.pdf

Abstract Catathelasmols C, D, and E, which had been isolated from Catathelasma imperiale as inhibitors for 11-hydroxysteroid dehydrogenases, were comprehensively semisynthesized from commercially available D-glutamic acid. The key synthetic intermediate, (R)-pentane-1,2,5-triol, was site-selectively acetylated by treatment with vinyl acetate and Candida antarctica lipase B (Novozym 435) in tetrahydrofuran (THF) at 25°C to furnish 1,5-diacetate (catathelasmol E, quantitative). The acetylation occurred site-selectively on the primary alcohols at the C-1 and C-5 positions over the secondary alcohol at the C-2 position. Dichromic acid oxidation provided 2-oxopentane-1,5-diyl diacetate (catathelasmol C, 78%). Burkholderia cepacia lipase-catalyzed transesterification with methanol in THF at – 5°C proceeded preferentially on the acetate at C-1 located adjacent to the C-2 carbonyl group over the other terminal acetate at the C-5 position. 5-Hydroxy-4-oxopentyl acetate (catathelasmol D) was obtained in 53% yield.