Georges Jeminet

Chiral recognition properties of spiroacetal polyethers using electrospray ionisation mass spectrometry

Associations between monocyclic or bicyclic polyethers (1 – 10) incorporating a chiral spiroacetal moiety and ammonium enantiomeric pairs of phenylglycine methyl ester (G1) or phenyl glycinol (G2) were studied by Electrospray Ionisation Mass Spectrometry by the enantiomer-labelled method. Several spiro-crowns and spiro-cryptands showed chiral recognition properties.

Study by NMR of the mode of action of monensin on Streptococcus faecalis de-energized and energized cells

Streptococcus faecalis was used as a bacterial model for studying the mode of action of monensin by NMR investigations. Experiments were carried out in two states, characterized by several complementary methods: (i) the resting (de-energized) cell which was considered as an inert biological membrane, on which cationic transport induced by the ionophore alone can be investigated; (ii) the active (energized) cell where the ionophore-sensitive response of the living organism, particularly the cation pumps and the glycolysis, is probed. Studies of resting cells were performed, with changing external ionic concentrations, in the presence of monensin, which is preferentially a sodium carrier. Internal and external Na+ and H+ were followed by corresponding 23Na and 31P (inorganic phosphate) NMR resonances, K+ fluxes were measured by atomic absorption. It was shown that the induced cationic movements were linked to the existing ionic gradients for K+ and Na+. 31P and 13C NMR spectra for the intermediary metabolites detected in active cells showed that glycolysis is dramatically modified in the presence of monensin.

SEMI-SYNTHESIS OF A23187 (CALCIMYCIN) ANALOGS

Semisynthesis of two demethylamino A23187 with a methyl group in the 4- or 5-position on the benzene ring were carried out via the cleavage of A23187 oxazole ring and rebuilding of modified benzoxazoles. These compounds were shown to release Ca++ and MG++ from mitochondria and to keep part the antibacterial activity of the natural metabolite.

2- And 8-functionalized 1,4,7,10-tetraoxaspiro[5.5]undecanes. II: Synthesis of (+)-E,E and (±)-Z,E structures from chiral isopropylideneglycerols

Abstract Using a short synthetic protocol, the enantiomerically pure ( + )-E,E title compound was made from (S,S)-diisopropylidenetriglycerol 4 in order to obtain a reference for correlations in this unexplored series. Analogously (S,R)-diisopropylidenetriglycerol 11 would afford the (±)-Z,E isomer which was also prepared. Conformations were deduced from 1 H NMR data.

Chiral 2- and 8-functionalised 1,7-dioxaspiro[5.5]undecanes via asymmetric dihydroxylation

Abstract Asymmetric dihydroxylation with AD-mix-α [or AD-mix-β] carried out on an appropriate ketodiene precursor afforded (2S, 6S, 8S) [or (2R, 6R, 8R)] 2,8-dihydroxymethyl-1,7-dioxaspiro[5.5]undecane. Subsequent synthesis of (+)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane (insect pheromone) and (+)-2-iodomethyl-8-acetyloxymethyl-1,7-dioxaspiro[5.5]undecane are described.

Synthesis of a biomimetic model of calcimycin (A 23187) with a demethylated skeleton

Abstract A demethylated model ( 15 ) of Calcimycin ( 1 ) has been synthesized from the known 2,8-dibromo-1,7 dioxaspiro (5.5) undecane ( 6 ) ; biphasic extraction experiments indicated a net decrease of affinity towards Mg++ and Ca++ for ( 15 ) versus ( 1 ).

Interaction of the calcium ionophore A.23187 (Calcimycin) with Bacillus cereus and Escherichia coli

Ionophores isolated from bacterial strains, and especially A.23187, are efficient antibiotics against Gram‐positive bacteria and devoid of activity on Gram‐negative species. This difference in activity was attributed to the outer membrane of Gramnegative bacteria which is presumably impermeable to these very hydrophobic compounds. In this context, the partition of the calcium ionophore A.23187 between bacteria and the medium was studied on Escherichia coli (Gram‐negative) and Bacillus cereus (Gram‐positive) using, on the one hand, fluorimetric measurements and, on the other hand, radioautographic analysis of bacteria incubated with the [3H]‐labelled ionophore. Although the first method did not give a definitive answer, the second one clearly showed that the tritiated metabolite was only incorporated into B. cereus.

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.

2- and 8- functionalized 1,4,7,10-tetraoxaspiro[5.5]undecanes. I. Synthesis of (±)-E,E and (±)-Z,E structures.

Abstract The synthesis of (±)-E,E and (±)-Z,E 2,8-dihydroxymethyl-1,4,7,10-tetraoxaspiro[5.5]undecane is described. The selective modification of one sidechain is examined for the (±)-E,E isomer, and a tetraoxygenated analogue of a commonly encountered insect pheromone is prepared.