Design and synthesis of ether derivatives of spliceostatin A and their biological evaluation towards prostate cancer treatment. (12th January 2023)

• Record Type: Journal Article
• Authors: Hirabayashi, Satoru; Li, Yue; Ohta, Noriko; Ishibashi, Airi; Yoshikawa, Yusuke; Lin, Bangzhong; Fumimoto, Megumi; Takehara, Tsunayoshi; Nunomura, Kazuto; Suzuki, Takeyuki; Haruta, Junichi; Nimura, Keisuke; Arisawa, Mitsuhiro
• Is Part Of: Tetrahedron letters. Volume 114(2023)
• Publication Date: 2023-01-12
• Subjects: CRPC castration resistant prostate cancer; -- AR androgen receptor -- AR-V7 AR splicing variant 7 -- SSA spliceostatin A -- DMP Dess−Martin periodinane -- DIBAL i-Bu2AlH -- PivCl t-BuCOCl -- TBS Si-t-BuMe2 -- TBAF Bu4NF -- VO(acac)2 vanadyl acetylacetonate -- TBS-BEZA O-(t-butyldimethylsilyl) benzanilide -- BtSH 2-mercaptobenzothiazole -- DIAD diisopropyl azodicarboxylate -- m-CPBA m-chloroperoxybenzoic acid -- LHMDS LiN(SiMe3)2 -- Et3N triethyl amine -- DMAP N, N-dimethyl-4-amino pyridine.; Prostate cancer -- splicing variant -- spliceostatin A -- Hydrogen bond; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2022.154288
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Abstract: To confirm the hypothesis that the terminal epoxide structure of spliceostatin A may be active through hydrogen bond formation, we designed and synthesized novel ether derivatives of spliceostatin A, whose terminal epoxide is replaced with an ether-based moiety capable of hydrogen bond formation. The results of biological evaluation against AR-V7 and the conformational analysis of each derivative suggest that the terminal epoxide moiety of spliceostatin A expresses its activity through covalent bond formation rather than hydrogen bond formation.