角蒿生物堿及鎮痛活性物質(zhì)

天然產(chǎn)物研究與開(kāi)發(fā)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角蒿生物堿及鎮痛活性物質(zhì)遲玉明1*,中村基之1,趙唏瑛1,吉澤豐吉1,閻文玫2,橋本文雄3,野原稔弘3,櫻田忍4(1.日本正和藥品株式會(huì )社,茨城3191535;2北京中醫藥大學(xué),北京10009;3熊本大學(xué),熊本862093;4東北藥科大學(xué),仙臺981-0905)摘要:角蒿( Incarvillea sinensis)為透骨草的主要來(lái)源之一,稱(chēng)為“羊角透骨草”,具有祛風(fēng)除濕、消腫止痛之功效。從其全草分離得到了多種新的單萜生物堿和大環(huán)精胺類(lèi)生物堿,其中單萜生物堿之一角蒿酯堿( incarvillateine),具有很強的鎮痛活性,且作用機理不同于嗎啡。角蒿酯堿已成為開(kāi)發(fā)新型非麻醉性鎮痛新藥的重要先導化合物本文對角蒿的化學(xué)成分、鎮痛活性、作用機理和構效關(guān)系的研究作一綜述。關(guān)鍵詞角蒿;單萜生物堿;角蒿酯堿;鎮痛活性中圖分類(lèi)號: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中國煤化工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遲玉明等:角蒿生物堿及鎮痛活性物質(zhì)363N(1md