Yves Blache

Efficient synthesis of novel dipyridoimidazoles and pyrido[1′,2′;1,2]imidazo[4,5-d]pyridazine derivatives

Abstract Novel dipyrido[1,2- a ;3′,4′- d ]imidazoles 7a – d , dipyrido[1,2- a ;4′,3′- d ]imidazoles 8a , c and pyrido[1′,2′;1,2]imidazo[4,5- d ]pyridazine derivatives 9a – d were synthesized by two pathways: thermal electrocyclic reaction of 3-alkenylimidazopyridine-2-oximes 10 and direct condensation of ethyl glycinate (or hydrazine) with 2,3-dicarbonylimidazo[1,2- a ]pyridines 11 .

Aminoimidazo[1,2-a]pyridines: regioselective synthesis of substituted imidazonaphthyridines, azacarbolines and cyclazines

Abstract In order to study the regioselectivity of thermal cyclocondensation, aminoimidazo[1,2-a]pyridines (AIP) 5a–e were prepared, further converted into iminophosphoranes 7a–e , and ultimately converted regioselectively in angular annulated imidazonaphthyridines (IN) 8a , 10a , 11a , 12a or linear annulated dipyridoimidazole (DPI) 17a . From 2-substituted derivative 23 , the peri annulated product 24a was obtained. The starting amines 5a–f reacted with aldehydes to yield regioselectively IN 8a–c , 10a–c , 11a–c , 12a,b , DPI 16a–e , 17a–d and TIBO like structures (±)-13 and 24a–c , as proved by X-ray analysis. The 1,2- or 1,4-addition between amines and α,β-unsaturated aldehydes concerning the pyridine and imidazole moieties is discussed in the light of these results.

Heterocyclic enaminones: Photochemical synthesis of 6,7,8,9-tetrahydro-5H-pyrido[2,3-b]indol-9-ones

Abstract The synthesis of 6,7,8,9-tetrahydro-5 H -pyrido[2,3- b ]indol-9-ones from arylenaminones is described. Two “routes” have been investigated: a radical process through a photochemical reaction, and a catalytic process through an arylpalladium complex.

Synthesis of Azacarbazoles

Photocyclization of N-Benzylenaminone (7) led to azacarbolinones products which were fragmented to unexpected aldehydes (9) and (11)

Efficient Synthesis of New Polyfunctionalized Thiadiazaacenaphthylenes from Imidazo[1,2-a]pyridines

New heterocycles containing sulfur and nitrogen with an azaindolizine moiety were synthesized. The imidazo[1,2-a]pyridine-2,5-dicarboxylates (9a, b, 10a, b) and 5-formylimidazo[1,2-a]pyridine-2-carboxylates (17a, b) treated with ethyl thioglycolate and lithium hydroxide underwent ring closure yielding the multifunctional[2,3,3]cyclazines (13) and (18). Under similar conditions, the imidazo[1,2-a]pyridinecarbaldehydes (22a, b) and (29a, b) were converted into the linearly cyclized compounds thieno[3,2-b]imidazo[1,2--a]pyridines (23, 31) and a peri annulated product thiadiazaacenaphthylene (30).

CONVERSION OF IMIDAZO[1,2-a]PYRIDINES INTO PYRIDO[1,2-e]PURINES

Intramolecular cyclization of 2-acylated amine, carbamoyl and 3aminoimidazo[1,2-a]pyridine-2-carbonitrile allows access to pyrido[1,2-e]purines. Aminodipyrido[1,2-a:31,2-d]imidazoles (Glu-P-1 and Glu-P-2 la.b). isosteric compounds of 2-aminofluorene, were recently identified as highly mutagenic compounds (1). These molecules modify DNA by intercalation between base pairs or covalent binding to C-8 of guanine (2). They also induce transformation of embryonic hamster cells (3). Recently it was demonstrated that N-acetyl derivative of Glu-P-1 is the major active metabolite in rat bile (4) . In a series of studies on the heterocyclization of the novel compounds having the Imidazopyridine skeleton, we have studied the structural conversion of azaindolizine derivatives to the pyridopurine skeleton 2..

REACTIVITY OF 6,7,8,9-TETRAHYDROPYRIDO[1,2-a]BENZIMIDAZOL-9-ONE : SYNTHESIS OF PYRROLOPYRIDOBENZIMIDAZOLES

reactivity of 6,7,8,9-tetrahydropyrido[l,2-a]benzimidazol-9-ones 1 to give the 1,4 and 1,3-dicarbonyl compounds 2 and 3 is reported Further heterocyclisation of these derivatives is investigated in view of the obtention of the tetracyclic pyrrolic frameworks 4 and 5. Introduction As part of studies related to the biological activities of triand tetracyclic heterocycles with a bridghead nitrogen (1), we initiated a program aimed at examining the synthesis and cytotoxicity against resistant tumor cells of new tetracyclic derivatives of azacarbazoies. Since the pyrido[l,2-a]benzimidazole ring system has been found to exhibit anticancer properties by Badaway and co-workers (2), a number of studies have been directed toward this heterocycle. These investigations showed good activities for compounds substituted on ring A. As a first approach of modifications which should be integrated into ring C, we reported the regioselective synthesis of some pyrazolo derivatives and and their antitumor activities in vitro against some resistant cell lines (MDR+)(3). In order to determine the effect of the position of nitrogen atoms on such heterocyclic compounds, we describe now our investigations concerning the reactivity of the 6,7,8,9-tetrahydropyrido[l,2-a]benzimidazol-9-one 1 system in view of the synthesis of pyrrolo derivatives 4 and 5.

SYNTHESIS AND REACTIVITY OF 6,7,8,9-TETRAHYDROPYRIDO[1,2-a ] BENZIMIDAZOL-9-ONE

Synthesis of a tricyclic imidazo[l,2-a]pyridine system (1), and reactivity of the cyclohexyl moiety are described. Tetrahydrocarbazoles are of great interest for the construction of many complex alkaloids belonging to the Murrayaquinones families (1) . As a part of our program on azaindolic structures, we have recently described the photochemistry of azineenaminones with a view to construct azacarbazole skeleton (2) . In continuation of our studies, we now develop a program concerning the synthesis and antitumoral potentiality of modified murrayaquinone ring system 2. In this context, the synthesis of the tricyclic bridgehead heterocyclic system 1, and our preliminary investigations on the reactivity of the cyclohexyl moiety are reported (scheme 1) . Scheme 1 Ο

Synthetic studies on indole alkaloids VIII. 1 Synthesis and reactivity of asymmetric 2-indolyi-4-methylenepiperidines

Abstract The synthesis of asymmetric 2-indolyl-4-methylenepiperidines 8–11 and 14–15 by condensation of an aminoallylsilane with an indole carbaldehyde, followed by intramolecular cyclization of the intermediate, is described. The reactivity of N-(2-hydroxyethyl)indolylpiperidines 9 and 14 with KtBuO to give indolo[2,3-a]quinolizidines is studied. Some unexpected results are obtained due to the influence of the α-phenyl ring.

PHOTOCHEMISTRY OF POLYHALOGENATED HETEROCYCLIC ENAMINONES: COMPETITION BETWEEN CYCLIZATION AND DEHALOGENATION

Photochemistry of polvhalogenated enaminones is described under various conditions to give functionalized tetrahulroazacarbazolone (9, 15). Starting enaminones (2, 7, 14) also underwent competitive dehalogenations creating a sei o f .secondary products. Mechanistic aspect of the reactions are considered .