NITROGEN BRIDGEHEAD COMPOUNDS .86. SYNTHESIS AND REACTIVITY OF 7,12-DIHYDROPYRIMIDO[1',2'1,2]PYRIDO[3,4-B]INDOL-4(6H)-ONES - DEBENZOLOGUES OF RUTAECARPINE ALKALOIDS

摘要

A series of 7,12-dihydropyrimido[1',2':1,2]pyrido[3,4-b]indole-4(6H)-ones was prepared by Fischer indolization of 9-arylhydrazono-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-ones. Quantum chemical calculations (ab initio and AM1) indicate that position 3 of 7,12-dihydropyrimido[1',2':1,2]pyrido-[3,4-b]indole-4(6H)-one can be involved in electrophilic substitutions, while position 2 is sensitive towards nucleophilic attack. Bromination of 6-methyl-7,12-tetrahydropyrimido[1',2':1,2]pyrido-[3,4-b]indol-4(6H)-one 16 with bromine afforded 3-bromo derivative 25, which was reacted with cyclic amines to give 2-amino-7,12-dihydropyrimido[1',2':1,2]py 26-30 in an addition-elimination reaction. Vielsmeier-Haack formylation of compound 16 gave 12-formyl 31 and 3,12-diformyl 32 derivatives (an N-formyl-1-deaza derivative of nauclefidine alkaloid 34) at 60 degrees and 100 degrees, respectively. 3,12-Diformyl compound 32 was oxidized to 3-carboxyl derivative 33 with potassium permanganate. The quaternary salt 35, obtained from compound 16 with dimethyl sulfate, suffered a ring opening on the action of aqueous sodium hydroxide. The new compounds have been characterized by elemental analyses uv, H-1 nmr and in some cases by C-13 ruler, CD spectra and X-ray investigations. [References: 56]