Article

Dibenzocyclooctadiene Lignans from Kadsura polysperma and Their Antineurodegenerative Activities

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, People's Republic of China.
Journal of Natural Products (Impact Factor: 3.8). 02/2012; 75(2):249-56. DOI: 10.1021/np200937h
Source: PubMed

ABSTRACT

Eleven new dibenzocyclooctadiene lignans, polysperlignans A-K (1-11), and eight known analogues (12-19) were isolated from the stems of Kadsura polysperma. Their structures and absolute configurations were established using a combination of MS, NMR, CD, and single-crystal X-ray diffraction techniques. Selected compounds were evaluated for activity against β-amyloid- or hydrogen peroxide-induced neurotoxicity on PC12 cells, and 1, 2, 4, 5, 13, and 16 showed statistically significant neuroprotective effects in these in vitro assays.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Dibenzocyclooctadienes (DBCOD) are a class of plant-derived natural products that exhibit a broad range of biological activities. These include cytotoxicity, anti-hepatitis-B activity, inhibition of HIV replication and of NO production and activity. None of the fully substituted DBCODs have been prepared before. 2,2'-Dipropargylbiphenyls undergo highly regio- and atropselective cyclizations mediated by a [B-Sn]reagent, 1-trimethylstannyl-2,5-diazaborolidine (Me3Sn-B[-N(Me)CH2CH2(Me)N-], in the presence of Pd(II)-catalysts, to give highly functionalized DBCOD precursors. The configuration of the newly created, axially chiral, 1,2-bis-alkylidene moiety is controlled by the resident chirality of the starting biphenyls and the configurations of the benzylic positions. New chemistry of the bis-alkylidenes described in this paper enables the first total syntheses of a wide variety of DBCOD natural products, fully functionalized at the cyclooctadiene ring. These include ananolignans B, C, D, F, interiotherin C, kadsuralignan B, tiegusanin D and schizanrin F. Revision of the structure of a key natural product, ananolignan B, is also reported. Key steps in the syntheses exploits the conformational features of the various DBCOD intermediates as revealed by NMR spectroscopy and X-ray crystallography.
    No preview · Article · Oct 2013 · Chemical Science
  • [Show abstract] [Hide abstract]
    ABSTRACT: (M)-Bicelaphanol A (1) and (P)-bicelaphanol A (2), two unprecedented dimeric trinorditerpenes existing as atropisomers, together with their monomer celaphanol A (3), were isolated from the root bark of Celastrus orbiculatus. The structures and absolute configurations of 1 and 2 were determined by spectroscopic and single-crystal X-ray diffraction analyses. Compound 1 exhibited a significant in vitro neuroprotective effect against a hydrogen peroxide-induced cell viability decrease in PC12 cells at 1 μM, while compounds 2 and 3 showed such effects at 10 μM.
    No preview · Article · Feb 2013 · Journal of Natural Products
  • [Show abstract] [Hide abstract]
    ABSTRACT: Lead Compounds from Medicinal Plants for the Treatment of Neurodegenerative Diseases is the second volume in the series, Pharmaceutical Leads from Medicinal Plants. This book includes key pharmacological and chemical evidence to support the selection of promising pre-clinical candidates for the treatment of neurodegenerative diseases. This important addition to the natural product and drug discovery literature contains the history, synonyms, medicinal uses, phytopharmacology, pre-clinical potential, and rationale for each plant selected. By providing critical evaluation of pharmacological data, mechanisms of action, and structural requirements for the development of future neuroprotective agents, this comprehensive reference is a beneficial resource for industry and academic scientists whose research focuses on neurodegenerative drug discovery and development. It incorporates compelling biological activity data and preclinical structure-activity relationships to help you choose promising lead molecules for further research. It includes primary source references to the most recent natural product discoveries in the field of neuroprotection in order to promote new drug discovery in this area. It contains detailed discussions of important neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Each plant section includes a critical evaluation of pharmacological, chemical, and toxicological evidence to support the use of the compound in drug discovery research in neurodegeneration.
    No preview · Book · Mar 2014
Show more