PROCESS FOR PREPARING CERTAIN PYRROLO 3,4- $i(b)QUINOLINES, CERTAIN 1H-PYRANO 3',4':6,7INDOLIZINO 1,2-$i(b)QUINOLIN-3,14(4H,12H)-DIONES, AND CERTAIN 8-METHYL-7-(OXOPROPYL)-INDOLIZINO 1,2-$i(b)QUINOLIN-9(11H)-ONES

摘要

The present invention provides a process for preparing certain pyrrolo(3,4-(b))quinolines, certain 1H-pyrano(3',4':6,7)indolizino(1,2-(b))quinolin-3,14(4H,12H)-diones, specifically camptothecin and its analogs, and certain 8-methyl-7-(oxopropyl)-indolizino(1,2-(b))quinolin-9(11H)-ones, specifically mappicine ketones and mappicines, said process comprising the step of intramolecular (4+2) cycloaddition of the N-arylimidate portion of a compound of formula (IV) where: X=OH, OAlCl2, Cl, Br, I, F, OR, OSO2CF3 or any good leaving group or H; R1=H, or OR, where R is an ester protecting group; R2=H, NO2, or a protected amine function; R3=H, C2H5, or a trialkylsilyl; R4=H or CH2COOEt; R5=COOMe or tosyl; or R4 and R5 are joined together to form a substituted pyridone (IVa): Y=H or Y,R1=-OCH2O-, formula in which A=H,COOR, or a functionnality for preparation of the hydroxymethyl (C-17) portion of an E ring lactone; B=H, OH, an appropriate leaving group such as halide or O(trifluoromethanesulfonate) or a functionality for preparation of C-(18-21) of the E ring lactone portion of camptothecin, with the unactivated acetylene portion of said compound.