Σύνθεση και μελέτη συμπυκνωμένων αζα- και διαζα- κυκλοαλκανο[b]ινδολίων και πολυκυκλικών παραγώγων της 1,2,3,4-τετραϋδρο-β-καρβολίνης

Abstract

The present Thesis is concerned with the synthesis and study of the structure of certain tetra- and pentacyclycic β-carboline ring systems, as well as fused aza- and diaza-cycloalkano[b]indole derivatives. The first goal of the work reported is the synthesis of β-carboline pentacycles through either N-acyliminium cyclization processes or tandem Ru-catalyzed olefin metathesis reactions from tricyclic β-carboline derivatives as starting materials. An effective route to pentacyclic indolo[2,3-a]quinolizine ring systems is described. Bischler Napieralski cyclization reactions of N-(ω-nitro-alkyl) indole derivatives 215α,β and N-acyliminium ion cyclization of the corresponding 3,4-dihydro-β-carbolines 216α,β afford the tetracyclic (±)-1-{(3aR,4S)-4-nitro-1,2,3a,4,5,6-hexahydro-3Η-indolo[3,2,1-de][1,5]naphthyridin-3-ylo}-2-propen-1-one (222α-1) and the (±)-1-[(3aR,4S)- and (±)-1-[(3aR,4R)-4-nitro-1,3a,4,5,6,7-hexahydro-3,7a-diazacycloheptano[jk]fluoren-3(2Η)-ylo]-2-propen-1-ones (222β-1 and 222β-2). Deprotonation of the C-14 of 222α or 222β and subsequent elimination of HNO2 gives directly the pentacyclic 1,2,5,6,12,13-hexahydro-3Η-indolo[3,2,1-de]pyrido[3,2,1ij][1,5]naphthyridin-3-one (233α) or 1,2,5,10,11,12,-hexahydro-3Η,4Η-3a,9b-diazabenzo[a]naphtho[2,1,8-cde] azoulen-3-one (233β) in good yields. The synthetic route to the dienyne-β-carboline derivatives 280 and 282 is described. These substrates do not cyclize under standard RCM conditions with any of the ruthenium catalysts used, most likely due to the incompatibility of the Ru-catalyst systems with the amine functional group. The second goal of the work reported, the synthesis of aza- cycloalkano[5,4-b] and diaza-cycloalkano[5,6-b]indoles, was accomplished with two different synthetic strategies. 1,3-Dipolar cycloaddition reactions of the nitrone 298 with methyl acrylate and dimethyl fumarate furnish the isoxazolidines 303α,β, 304α,β and 306α,β. The stereochemical and regiochemical features of the cycloaddition are discussed. Reductive cleavage of the cycloadducts 303α or 306α afford the pyrrolidinones 311 or 314, while similar reaction of the mixture of 4-regio-isomers 304α,β gives the mixture of 1,3-hydroxy-amines 315α,β. Treatment of 303α or 304α,β with hydrazine leads to the formation of the bridged azacyclononan[5,4-b]indole derivative 319 or the fused azacyclooctan[5,4-b]indole derivatives 320α,β respectively. N-acyliminium ion cyclization reactions of α-hydroxy-alkylamide 331 in acidic conditions leads to the hexahydro-1,3-diazocino[5,6-b]indole derivatives 335 and 336.