الفهرس 
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Abstract
Cancer and infectious diseases cause millions of deaths worldwide per year, and the number of affected persons and deaths are increasing steadily. The development of new chemotherapeutic agents for the treatment of cancer and microbial infections is still urgently needed to help to ensure the availability of new drug candidates to feed the preclinical pipeline. This will help to surmount current issues arising from the drawbacks of current drugs such as low efficacy, significant side effects and resistance. In this context, plants are still an important resource for the discovery of new drugs. Natural products have recently drawn renewed interests and attentions as the seed of novel medicines. However, availability of such natural products from nature tends to be severely limited. In order to develop novel medicines from natural products, sufficient amounts of compounds need to be provided for derivatization and biological testing. One of the goals of our thesis is to establish practical synthetic route for the natural products of medicinal importance. In addition, a variety of derivatives of the natural products will be synthesized for biological testing. Many naturally occurring compounds, including the minor alkaloid neocryptolepine 1 and major alkaloid cryptolepine 2, were isolated from the roots of the West African climbing shrub Cryptolepis sanguinolenta (Figure 1), a traditional herb used in folk medicine for the treatment of malaria. Both of the two tetracyclic heteroaromatic compounds are linearly fused indoloquinolines and exhibit a wide scope of biological activity. Therefore, we selected neocryptolepine 1 as the lead compound for the development of a new drug because of its lower cytotoxic activity compared to cryptolepine 2
towards the DNA intercalation in addition alkaloids are known for their broad spectrum of pharmacological activity.
Figure 1. Indoloquinolines from Cryptolepis sanguinolenta
This thesis includes three chapters. The first chapter is the introduction which comprises an updated literature survey of the chemistry of neocryptolepine (indoloquinoline alkaloid from Cryptolepis sanguinolenta). This review included the most important methods of total synthesis of this alkaloid as well as their reactions and biological activities are considered.
The second chapter is devoted to results and discussion which consists of three parts:
The first part includes the preparation of chloroneocryptolepine (5) by the reaction of methyl-1H-indole-3-carboxylate 1 with aniline derivatives 2 to afford the intermediate methyl 2- (phenylamino)-1H-indole-3-carboxylates 3, by chlorination of 1 at C-2 position with N-chlorosuccinimide in the presence of 1,4- dimethylpiperazine followed by addition of the aniline derivatives 2 as trichloroacetate salt. Compounds 3 was further cyclized in boiling diphenyl ether to give 5,6-dihydro-11H-indolo[2,3- b]quinolin-11-one 4 which was dehydroxychlorinated with POCl3 to yield the corresponding 11-chloroneocryptolepine 5 in.