Denise Dugat

A short Synthesis of (±) N-benzyl aspidospermiden

(±) N-benzyl aspidospermideine is synthesized in seven steps via the trisubstituted hexahydrocarbazolone 4, reductive cyclization of this intermediate which is obtained photocyclization and Michael reaction with nitroethylene, creates simultaneously both E and D rings of the pentacyclic system.

NOVEL CRYPTAND ANALOGS INCORPORATING A CHIRAL SPIRAN MOIETY

Abstract Macrobicyclic polyethers based on the cryptand model displaying a chirality due to a spiran junction were synthesized from diamines 7 and 8. Results of attempted direct macrobicyclisation varied with the length the α,ω-oligoethyleneglycol ditosylates chain used as reagent. The expected structure was obtained only for triethyleneglycol ditosylate. The complexing properties of the diaza-octaoxa ligand 11, with alkaline and ammonium cations, were measured in THF by UV-Visible spectrophotometry.

Chiral macrocyclic polyethers incorporating a tetraoxaspiro[5.5]undecane or trioxa-azaspiro[5.5]undecane moiety

Abstract New macrocyclic polyethers possessing chirality due to a spiro ring junction are prepared from 2,8-dihydroxymethylated (+)-1,4,7,10-tetraoxaspiro[5.5]undecane 1 and (+)-1,4,7-trioxa-10-azaspiro[5.5]undecane 2 , both ( E,E ). N -Functionalization of compounds derived from 2 is also examined. The complexing properties of representative ligands 3 , 4 , 5 measured by spectrophotometry in THF, for alkaline and alkaline-earth cations, indicate that these spheric positively-charged species are weakly associated.

Macrocyclic 14-Membered Ring Diketal Dilactams: Evaluation of their Divalent Cation Binding Properties

The binding abilities of a new class of 14-membered ring ligands bearing diketal dilactam functions were explored by UV-visible spectrophotometry. Their formation constants, determined in THF solution, showed appreciable complexation with divalent cations (stability order: Sr2+≥Ca2+>Zn2+≥Mg2+>Ba2+) whereas no association was observed with monovalent cations. The stoichiometry of the complexes formed was essentially 1:1 although sometimes a low percentage (<10%) of 1:2 (cation–ligand) species was detected. The corresponding formation constants determined by computation (STAR program) were in the range 1.5<log β 11<4.8 and 4.4<log β 12<7.1. They depend significantly on the nature of the substituents. In addition, solvent extractions carried out in a water–chloroform system showed the highest constants (log K ex) for the most substituted macrocycles 7b and 7c (norephedrine series) with a lipophilic skeleton.

Structural Features in the Seven‐Membered vs. Fourteen‐Membered Ring Cyclization of Hydroxyamido Ketals Derived from β‐Amino Alcohols

Hydroxyamido ketals 1 and 3−12, prepared from β-amino alcohols, are obtained either as a single form with a trans (1 and 3−8) or cis (9) conformation in the R = H series or as two cis and trans rotamers in the R ≠ H series (10−12). − The cyclization of these compounds was studied under acidic conditions (PTSA) and over a well defined range of concentrations (c = 0.1−0.2 M). While cis amide 9 and mixtures of cis and trans rotamers 10−12 resulted practically exclusively in the formation of seven-membered ring lactams 22−25, trans compounds 1 and 3−8 afforded fourteen-membered ring bislactams 2, 13−18, the formation of which involves a dimerization. Macrocycles were obtained as three diastereomers in the chiral series 2, 13−16 and as two isomers in the achiral series 17 and 18. Nineteen macrocyclic bislactams have thus been synthesized.

Bis-14-membered ring diketal diamines: Synthesis and evaluation of their anti-HIV and anti-tumoral activities

Chiral and achiral macrocyclic bis-diketal diamines, analogs of bicyclam AMD 3100, were synthesized in three steps from the previously obtained 14-membered ring diketal dilactams. Their monoreduction with lithium aluminium hydride gave the corresponding diketal aminolactams. Coupling these with dibromo-p-xylene led to xylyl dimer compounds. A second reduction step yielded the expected bis-diketal diamines in the methyl and unsubstituted series. Biological tests on the unreduced and reduced dimers showed both weak anti-HIV and anti-proliferative activities for the bis-diphenyl diketal aminolactam 13b, with a mode of action probably different from that of AMD 3100.

Studies on the Selective Reduction of the Amide Link of Acyclic and Macrocyclic Amidoketals: Unexpected Cleavage and trans‐Acetalization with Red‐Al®

Abstract Selective reduction of the amide moiety of acyclic and macrocyclic amidoketals was studied in presence of various reagents (BH3 · Me2S, iBuAlH2, Red‐Al®, LiAlH4). The best results were obtained with lithium aluminium hydride in the presence of triethylamine traces, whereas borane dimethyl sulfide gave rise to a partial ketal reduction of the acyclic compound and Red‐Al® to a cleavage of the macrocyclic molecule accompanied by an unexpected trans‐acetalization.