Synthetic studies of isoindolobenzazepine and homoprotoberberine alkaloids
1
Issued Date
2023
Copyright Date
1990
Language
eng
File Type
application/pdf
No. of Pages/File Size
iv, 209 leaves : ill.
Access Rights
restricted access
Rights Holder(s)
Mahidol University
Bibliographic Citation
Thesis (Ph.D. (Organic Chemistry))--Mahidol University, 1990
Suggested Citation
Poolsak Sahakitpichan Synthetic studies of isoindolobenzazepine and homoprotoberberine alkaloids. Thesis (Ph.D. (Organic Chemistry))--Mahidol University, 1990. Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/89680
Title
Synthetic studies of isoindolobenzazepine and homoprotoberberine alkaloids
Alternative Title(s)
การศึกษาการสังเคราะห์อัลคาลอยค์ประเภทไอโซอินโดโลเบนซาซีพีนและโฮโมโปรโตเบอร์เบอร์รีน
Author(s)
Abstract
Lennoxamine, the natural isoindolobenzazepine, and its derivatives, were synthesized by two newly developed routes. In the first route, 2-ethoxycarbonylbenzyl-3,4-dihydroisoquinoline derivative was the key intermediate which could be readily synthesized by the N-alkylation of 3,4-dihydroisoquinoline with ethyl 2-chloromethylbenzoate derivative. This key intermediate, 2-ethoxycarbonylbenzyl-3,4-dihydroisoquinoline derivative was then treated with ethanolic potassium hydroxide or sodium hydroxide to give the dehydrolennoxamine derivative which could then be easily converted to the required alkaloid. In the second route, aldehydic lactam was used as the key intermediate. In this approach, the aldehydic lactam was synthesized by bis alkylation-acylation of phenethylamine derivative with ethyl2-chloromethylbenzoate derivative followed by formylation which was found to be conveniently carried out by the reaction of dichloromethyl methyl ether (CL2CHOCH3). The aldehydic lactam was then further treated with ethanolic potassium hydroxide or sodium hydroxide to give the dehydrolennoxamine derivativ which could be transformed to natural lennoxamine by catalytic hydrogenation in good yield. The above approaches could be extended to synthesize various isoindolobenzazepine alkaloids. The new approach to the synthesis of homoprotoberberine alkaloids was developed. The key step of the reaction involved the alkylation of the aromatic carbanion with 2-(2-bromoethyl)-1,3-dioxolane. The alkylation product was then converted to the homprotoberberine alkaloid by cyclization in the presence of formic acid further reduction with lithium aluminium hydride. Praziquantel, the pyrazionisoquinoline skeleton, and its analogue were prepared. The sequence of the reaction involved the condensation of phenethylamine with chloracetyl chloride and subsequent N-alkylation of 2-aminoacetaldehyde dimethyl acetal with the resulting chloro amide. The amino amide so obtained could by cyclized by sulfuric acid to give the key tricyclic amine. The praziquantel and various other derivatives were easily prepared by amidification of the derived amine with the appropriate acid chlorides
Degree Name
Doctor of Philosophy
Degree Level
Doctoral Degree
Degree Department
Faculty of Science
Degree Discipline
Organic Chemistry
Degree Grantor(s)
Mahidol University