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，这是世界上植物区系最丰富的地区之一，其中一些在泰国和马来西亚已被用作传统药物。我们希望扩大合成视野，最大限度地利用药物研究的发展来生产创新药物。本项目旨在探索从马来亚地区天然资源中开发一种以异喹啉和吲哚类生物碱为主的新药，主要研究结果如下：1.植物来源：(1)从马来西亚大花叶菊幼叶中分离得到一种新的具有高度共轭体系的新的Corynanthe型吲哚生物碱--(-)-9-甲氧基-3-甲氧基-β-内酯，其结构首先通过光谱分析推导，然后由光学纯的环氧酮和5-甲氧基-3，4-二氢-3，4-二氢-DHO-Caroline进行手性全合成确证。手性hplc分析表明，该天然产物中含有主要的…。(-)-对映体与(+)-对映体的比例为62：38。(2)通过对已知的三叶菊生物碱进行低温核磁共振谱分析和DDQ氧化的化学转化，对其结构进行了修正。海洋来源：(1)从泰国蓝色海绵Xestospongia sp.中分离得到三种新类型的肾霉素，即肾霉素J-L。这些化合物的~1H和~(13)C-核磁共振波谱数据是从亮蓝色海绵Haliclona cribricutis的甲醇提取物中分离得到的雷尼拉霉素H的结构修正的有用工具。(2)成功地从泰国毛壳藻Eteinassida sp.中发现了主要成分Eteinassidin 770(ET770)。在普吉岛周围种植，在开采前使用我们与KCN的特殊技术。ET 770很容易转化为ET 743，目前正在进行II期临床试验，因为它在临床前抗肿瘤试验中具有良好的疗效。其它：淡紫红链霉菌发酵液中发现的次要成分--红霉素R的结构由其酰化化合物的HMQC和HMBC确定。较少

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