- Enantioselective Conversion of Oligoprenol Derivatives to Macrocycles in the Germacrene, Cembrene, and 18-Membered Cyclic Sesterterpene Series
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A new enantio-and diastereoselective process has been developed for the efficient conversion of farnesol and other oligoprenyl alcohols to chiral 10-, 14-, and 18-membered cyclization products, including germacrenol, (+)-costunolide, 3-β-elemol, and epi-mukulol. The key cyclization reaction utilizes ω-bromo aldehyde substrates, a chiral ligand, and indium powder as the reagent at -78 °C and generates 10-, 14-, and 18-membered cyclic products in 70-74% yield and 94-95% ee.
- Reddy, D. Srinivas,Corey
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p. 16909 - 16913
(2018/12/14)
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- Syntheses and Biological Evaluation of Costunolide, Parthenolide, and Their Fluorinated Analogues
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Inspired by the biosynthesis of sesquiterpene lactones (SLs), herein we report the asymmetric total synthesis of the germacrane ring (24). The synthetic strategy features a selective aldol reaction between β,-unsaturated chiral sulfonylamide 15a and aldehyde 13, as well as the intramolecular α-alkylation of sulfone 21 to construct a 10-membered carbocylic ring. The key intermediate 24 can be used to prepare the natural products costunolide and parthenolide (PTL), which are the key precursors for transformation into other SLs. Furthermore, the described synthetic sequences are amenable to the total synthesis of SL analogues, such as trifluoromethylated analogues 32 and 45. Analogues 32 and 45 maintained high activities against a series of cancer cell lines compared to their parent PTL and costunolide, respectively. In addition, 32 showed enhanced tolerance to acidic media compared with PTL. To our surprise, PTL and 32 showed comparable half-lives in rat plasma and in the presence of human liver microsomes.
- Yang, Zhong-Jin,Ge, Wei-Zhi,Li, Qiu-Ying,Lu, Yaxin,Gong, Jian-Miao,Kuang, Bei-Jia,Xi, Xiaonan,Wu, Haiting,Zhang, Quan,Chen, Yue
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p. 7007 - 7020
(2015/09/22)
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- Absolute stereostructures and syntheses of saussureamines A, B, C, D and E, amino acid-sesquiterpene conjugates with gastroprotective effect, from the roots of Saussurea lappa
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From the methanolic extract of the dried roots of Saussurea lappa Clarke, Saussureae Radix, five amino acid-sesquiterpene conjugates, saussureamines A, B, C, D and E, were isolated together with a lignan glycoside, (-)-massoniresinol 4-O-β-D-glucopyranoside. Their stereostructures were determined on the basis of chemical and physicochemical evidence. In addition, saussureamines and the related amino acid-sesquiterpene conjugates were synthesized using a Michael type addition reaction of amino acid to the α-methylene-γ-lactone moiety of sesquiterpenes. Saussureamines A, B and C, costunolide and dehydrocostus lactone showed a gastroprotective effect on acidified ethanol-induced gastric mucosal lesions in rats. Saussureamines A also exhibited an inhibitory effect on gastric mucosal lesions induced by water-immersion stress in mice. (C) 2000 Elsevier Science Ltd.
- Matsuda, Hisashi,Kageura, Tadashi,Inoue, Yasunao,Morikawa, Toshio,Yoshikawa, Masayuki
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p. 7763 - 7777
(2007/10/03)
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