角蒿生物碱及镇痛活性物质

天然产物研究与开发NATURAL PRODUCT RESEARCH AND DEVELOPMENT205Vdl.17N.3Incarvilleae Alkaloids and Antinociceptive substancesCHI Yu-ming", NAKAMURA Motoyuki, ZHAO Xi-yingYOSHIZAWA Toyokichi', YAN Wen-mei, HASHIMOTO Fumio,, NOHARA Toshihiro, SAKURADA Shinobu2. Beijing University of Traditional Chinese Medicine and Pharmacy, Beijing3. Kumamoto University, Kumamoto 862-0973, Japan; 4. Tohoku College of pharmac9810905,JAbstract: Incanilloe sinensis LAM., a traditional Chinese medicine, has been used to treat rheumatism and to relieve painFrom the whole plants, a number of novel monoterpene alkaloids andlic spermine alkaloids have been identified. Oneof the monoterpene alkaloids, incarvillateine, demonstrated higher antinociceptive effect than morphine in the formalin test, andthe mechanism of antinociception was diferent from that of morphine. Incarvillateine has become an important lead compoundfor developing new natural medicinal drugs. In this paper, the chemical investigation as well as the biological activity and struc-ture-activity relationship were reviewedKey words: Incarvillea sinensis; monoterpene alkaloid; incarvillateine; antinociceptive effect角蒿生物碱及镇痛活性物质迟玉明1*,中村基之1,赵唏瑛1,吉泽丰吉1,阎文玫2,桥本文雄3,野原稔弘3,樱田忍4(1.日本正和药品株式会社,茨城3191535;2北京中医药大学,北京10009;3熊本大学,熊本862093;4东北药科大学,仙台981-0905)摘要:角蒿( Incarvillea sinensis)为透骨草的主要来源之一,称为“羊角透骨草”,具有祛风除湿、消肿止痛之功效。从其全草分离得到了多种新的单萜生物碱和大环精胺类生物碱,其中单萜生物碱之一角蒿酯碱( incarvillateine),具有很强的镇痛活性,且作用机理不同于吗啡。角蒿酯碱已成为开发新型非麻醉性镇痛新药的重要先导化合物本文对角蒿的化学成分、镇痛活性、作用机理和构效关系的研究作一综述。关键词角蒿;单萜生物碱;角蒿酯碱;镇痛活性中图分类号:06293pounds with one known compoundsen isolated. Ac-sources of the Chinese crude drug"Tougucao, and it is cording to their structures, these cocould be dimainly used in the north and northeast areas of China[. vided into two groups: monoterpeneds and macroWe had designed to assign the pharmacological active cyclic spermine alkaloidssubstance(s)from this plant. So far, a number of novel al- The absolute configuration of incarvilline(1), a core com-kaloids have been identified and one of the monoterpene pound of monoterpene alkaloid type, was determined by X-alkaloids,incarvillateine,was found to possess higher ray crystallography 2,3. Oxyincarviline(2)was 5-hydrantinociceptive effect than morphine in the formalin test ylated incarvilline(33. Incarvine A(3)(4 and incarvine Bwith a different mechanism(4)s were the esters of Hildebrant's acid and incar-Novel Alkaloids from I sinensisvilline.IncarvineC(5)6) was a deoxytetrahydro-denivtive of incarvine B, but the incarvilline esterified byFrom the whole plants of I. sinensis, seventeen novel com- Hildebrant's acid in a head position. Incarvine AN-oxide(6中国煤化工mwme,wsomto be(7)151CNMHGand incarvilline, andReceived February 7, 2005; Accepted March 22, 2005Corresponding author Tel: 81-293-427148; E-mail: chi-59@ unimatethis compound is an important intermediate of incarvillateine(8). Incarvillateine had a dimericcarvin d, and the structure was determ05Vol.17N.3迟玉明等:角蒿生物碱及镇痛活性物质363N(1md