Synthesis and chemical reactivity studies of some new heterocycles utilizing enamines as precursors / Ahmed Gamal Ahmed Mostafa ; Supervised Said Ahmed Soliman Ghozlan , Ismail Abdelshafy Abdelhamid

Thesis (M.Sc.) - Cairo University - Faculty of Science - Department of Organic Chemistry

The thesis is composed of an introductory part and two original parts. In the first part, hexahydroquinolines and their fused derivatives are obtained in good to excellent yields by proceeding through a simple, mild, and ef{uFB01}cient procedure including the reaction of enamines with substituted cinnamonitriles using DABCO, peperidine or Chitosan as catalysts. The regiooriantation of Michael-addition was established with not doubt using the 2D-HMBC spectroscopy. In the second part, novel series of the cyclic 2-oxindole derivatives incorporated 2-amino-tetrahydroquinolin-5-one are prepared. The structure of the prepared compounds was elucidated using the different spectral tools. The region-orientation of the reaction products was elucidated through NOE difference experiment as well as, through using substituents on ortho position to affect further cyclization. Antitumor and antimicrobial evaluations were performed on the prepared compounds. Most of these compounds exhibit high to moderate antimicrobial activity. With respect to, the antitumor activity, the compounds showed more potent cytotoxic effect only toward human breast cancer MCF-7. Also we have found that derivatives containing ester group as (8c, 11b, 14b, and 15b) are more active than those contain cyanide group as (8a, 11a, 14a, and 15a). Moreover, the compounds 15b and 8b are the most active derivatives in this group. These two compounds showed apoptotic inhibition of proliferation of human breast adenocarcinoma MCF-7 cells through DNA fragmentation, induction of the tumor suppressor protein P53, induction of caspase-9, and finally through the inhibition of angiogenesis by decreasing Vascular endothelial growth factor (VEGF) expression and secretion

Issued also as CD