Medicinal Chemistry on Alkaloids from Plants in Malaya Area

由于大量的热带植物生长在马来亚地区，这是世界上最丰富的植物区系之一，其中一些已被用于泰国和马来西亚的传统医学。我们希望尝试获得一个扩大的综合观点，并充分利用制药研究的发展来生产创新药物。本项目主要从马来亚地区的天然资源中开发一种新的药物，主要是异喹啉和吲哚类生物碱，我们的研究结果总结如下：1。植物来源：（1）从马来西亚产的美绣线菊（Mitragyna speciosa）的嫩叶中分离得到一个新的柯里宁型吲哚生物碱，（-）-9-甲氧基美绣线菊内酯，具有高度共轭体系，其结构经光谱分析和手性全合成得到证实。手性HPLC分析表明，该天然产物中主要含有 关于我们 y（-）-对映异构体与（+）-对映异构体的比例为62：38。(2)通过低温核磁共振谱分析和DDQ氧化法化学转化，修正了从马来西亚的美帽菊中分离得到的吲哚生物碱mitragynine的结构.海洋来源：（1）从泰国蓝海绵Xestospongia sp.中分离得到三种新的雷尼霉素类化合物，即雷尼霉素J-L。这些化合物的详细的~ 1H-和~ <13>1C- NMR光谱数据是最近从亮蓝色海绵Haliclona cribricutis的甲醇提取物中分离得到的雷尼霉素H的结构修正的有用工具。(2)我们已经成功地发现海鞘素770（Et 770）作为主要成分，在很多从泰国被囊动物，海鞘属。生长在普吉岛周围，使用我们的特殊技术与KCN提取前。Et 770很容易转化为Et 743，由于其在临床前抗肿瘤试验中的有效性，目前正在进行II期临床试验。其他：用酰化化合物的HMQC和HMBC法测定了已被发现为天蓝链霉菌（Streptomyceslaavulae）培养物中的次要组分的沙夫霉素R的结构。少

As a large number of tropical plants grow wild in the Malaya area that is one of the richest floristic regions of the world, some of which have been used in the traditional medicine in Thailand and Malaysia. We wish to try to get an enlarged synthetic view and to produce innovative drugs making the best use of developments in pharmaceutical research. This project is exploring the development of a novel drug, mainly isoquinoline and indole alkaloids, from natural source in Malaya area and our results are summarized as follows :1. Plant sources : (1) A new Corynanthe-type indole alkaloid, (-)-9-methoxymitralactonine having a highly conjugated system was isolated from the young leaves of Mitragyna speciosa in Malaysia, and its structure was first deduced by spectroscopic analysis and then confirmed by chiral-total synthesis starting from optically pure epoxy-ketone and 5-methoxy-3, 4-dihydro-β-carboline. The chiral HPLC analysis demonstrated that the natural product contained predominantl … More y the (-)-enantiomer over (+)-enantiomer in the ratio of 62 : 38. (2) The structure of mitragynaline, an indole alkaloid isolated from Malaysian Mitragyna speciosa was revised by analysis of the NMR spectra measured at low temperature and by chemical transformation with DDQ oxidation from the known alkaloid mitragynine.2. Marine sources : (1) Three new types of renieramycins, namely renieramycins J-L, have been isolated from a Thai blue sponge, Xestospongia sp. The detailed ^1H- and ^<13>C- NMR spectral data of these compounds is a useful tool in structure revision of renieramycin H which was recently isolated from the methanol extract of the bright blue sponge Haliclona cribricutis. (2) We have succeeded to find ecteinascidin 770 (Et 770) as major components in a lot from a Thai tunicate, Ecteinascida sp. growing around Phuket Island, using our special technique with KCN before extraction. Et 770 is easily converted to Et 743, which is currently undergoing phase II clinical trials as a result of its promising efficiency in preclinical antitumor tests.3. Others : The structure of saframycin R which has been discovered as minor components of saframycin A cultures of Streptomyces lavendulae, was determined by HMQC and HMBC of its acylated compound. Less