2000 Fiscal Year Final Research Report Summary
Medicinal Chemistry on Alkaloids from Plants in Malaya Area
| Project/Area Number |
10044325
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| Research Category |
Grant-in-Aid for Scientific Research (A).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemical pharmacy
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| Research Institution | MEIJI PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
KUBO Akinori MEIJI PHARMACEUTICAL UNIVERSITY, FACULTY OF PHARMACY, PROFESSOR, 薬学部, 教授 (60097201)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAYAMA Hiromitu CHIBA UNIVERSITY, FACULTY OF PHARMACY, ASSOCIATE PROFESSOR, 薬学部, 助教授 (90171561)
AIMI Norio CHIBA UNIVERSITY, FACULTY OF PHARMACY, PROFESSOR, 薬学部, 教授 (30009170)
SAITO Naoki MEIJI PHARMACEUTICAL UNIVERSITY, FACULTY OF PHARMACY, ASSISTANT PROFESSOR, 薬学部, 講師 (80142545)
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| Project Period (FY) |
1998 – 2000
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| Keywords | Mitragyna spociosa / indole / isoquinoline / marine natural product / structure elucidation / total synthesis / opioid / antitumor activity |
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| Research Abstract |
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
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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
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