Asymmetric Total Synthesis of Shizukaol J, Trichloranoid C and Trishizukaol A. (28th February 2022)

• Record Type: Journal Article
• Authors: Wang, Xiao; Wang, Zhuang; Ma, Xianjian; Huang, Zhengsong; Sun, Ke; Gao, Xiang; Fu, Shaomin; Liu, Bo
• Is Part Of: Angewandte Chemie. Volume 134:Number 17(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-28
• Subjects: Asymmetric Total Synthesis -- Cascade Reactions -- Phase Transfer Catalysts -- Sesquiterpenoids; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202200258
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: The asymmetric total synthesis of three lindenane sesquiterpenoid oligomers, shizukaol J, trichloranoid C and trishizukaol A, has been accomplished concisely in 15, 16 and 18 longest linear steps, respectively. The expeditious construction of molecular architectures was facilitated by Nelson's catalytic asymmetric ketene–aldehyde cycloaddition, a sequence of allylic alkylation/reduction/acidic cyclization to forge a lactone, and a double aldol condensation cascade to construct the 5/6 bicyclic system. Diastereoselective nucleophilic substitution promoted by a phase transfer catalyst constructed the C11 quaternary stereogenic center, thus prompting synthetic efficacy toward shizukaol J. The synthesis of trichloranoid C and trishizukaol A was achieved after a cascade involving furanyl diene formation and a Diels–Alder reaction, as well as a one‐pot sequence involving furan oxidation and global deprotection. Furthermore, our biological evaluation revealed that two compounds exhibited unexpected toxicity against tumor cell lines. Abstract : Through application of a convergent strategy, the asymmetric total synthesis of three oligomeric lindenane sesquiterpenoids has been achieved concisely in 15, 16 and 18 linear steps, respectively. Furthermore, a biological evaluation revealed that two compounds in this study exhibited unexpected toxicity against tumor cell lines, which might be of high interest for pharmaceutical research.