- Scalable Total Synthesis of (+)- And (-)-Codonopiloneolignanin A via Ti(IV)/NHC Cooperative Control Highly Enantioselective Dimerization of Multisubstituted Cinnamaldehyde
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The first gram-scale asymmetric total synthesis of (+)- and (-)-codonopiloneolignanin A has been achieved from multisubstituted cinnamaldehyde in four steps with 37% overall yield. The synthetically challenging tricyclic [5, 3, 0, 03,8] decane skeleton was efficiently constructed via a highly enantioselective dimerization of multisubstituted cinnamaldehyde, followed by a sequence of cascade reactions including Prins cyclization, cation mediated cyclization, and deprotection. Furthermore, the scope of NHC-catalyzed/Ti(IV)-mediated synergistic control multisubstituted cinnamaldehyde dimerization was investigated. Significantly, the bioactivity of codonopiloneolignanin A and its enantiomer, particularly scarce in nature, was tested and showed good anticancer activity.
- Li, Xiangxin,Yong, Huaya,Fan, Xiaohong,Zheng, Yajuan,Wang, Zhen,Xie, Zhixiang
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supporting information
p. 6573 - 6577
(2021/08/18)
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- Receptor activity and conformational analysis of 5′-halogenated resiniferatoxin analogs as TRPV1 ligands
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A series of 5′-halogenated resiniferatoxin analogs have been investigated in order to examine the effect of halogenation in the A-region on their binding and the functional pattern of agonism/antagonism for rat TRPV1 heterologously expressed in Chinese hamster ovary cells. Halogenation at the 5-position in the A-region of RTX and of 4-amino RTX shifted the agonism of parent compounds toward antagonism. The extent of antagonism was greater as the size of the halogen increased (I > Br > Cl > F) while the binding affinities were similar, as previously observed for our potent agonists. In this series, 5-bromo-4-amino RTX (39) showed very potent antagonism with K i (ant) = 2.81 nM, which was thus 4.5-fold more potent than 5′-iodo RTX, previously reported as a potent TRPV1 antagonist. Molecular modeling analyses with selected agonists and the corresponding halogenated antagonists revealed a striking conformational difference. The 3-methoxy of the A-region in the agonists remained free to interact with the receptor whereas in the case of the antagonists, the compounds assumed a bent conformation, permitting the 3-methoxy to instead form an internal hydrogen bond with the C4-hydroxyl of the diterpene.
- Lim, Kwang Su,Kang, Dong Wook,Kim, Yong Soo,Kim, Myeong Seop,Park, Seul-Gi,Choi, Sun,Pearce, Larry V.,Blumberg, Peter M.,Lee, Jeewoo
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scheme or table
p. 299 - 302
(2011/02/27)
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