Marc J. O. Anteunis

Preferential conformation of the endogenous opiate-like pentapeptide met-enkephalin in DMSO-d6 solution determined by high field 1H NMR

Abstract A preferential conformation of the endogenous opiate-like pentapeptide Met-Enkephalin in DMSO-d6 solution was proposed from high field 1H NMR experiments at variable temperature and complete analysis of the coupling constants in relation with conformational energy steric maps. This conformation is characterized by a highly folded secondary structure with a βI turn involving a head-to-tail interaction and a quasi-axial position of the methionine side chain. The N-terminal Tyr-Gly moiety which exhibits a relative degree of freedom shows all the steric requirements found in opiates for a stereospecific interaction with the receptor. All these results are discussed in relation with the physicochemical and biological properties of opiate-like peptides.

NMR-experiments on acetals—part 32 : Dependency of geminal coupling constants of methylene groups on electronegativity, bond length and free orbital overlap of adjacent lobes an empirical relationship as a tool for conformational description

Abstract An equation, obtained by iterative fitting of experimental data in some 1,3-diheterocyclic, monocyclic and alicyclic compounds, is proposed. This enables prediction of 2J(XCH2Y) as depending on three main contributions: the Pauling electronegativities of X and Y, the bond distances CX and CY and the mutual orientation of the free orbitals and σ(CH) bonds. For the reading of the quantitative contribution to 2J by the latter phenomenon (p-σ “parallelity effect”) a monogram is presented allowing prediction of the geminal coupling values and conformational discussions in (X,Y-dihetero) cyclic compounds with X and/or Y = S, O, Se, C.

New synthesis of pipecolic acid and analogs

Abstract Pipecolic acid congeners are synthesised from α-cyanoamides, obtained by substitution of α-methoxyamides with trimethylsilyl cyanide in an alternative route via oxidation of amidoalkylationproducts of the α-methoxyamides.

Solution conformation of the ionophore A23187 and its magnesium salt

Abstract The analysis of proton nmr spectra at 300 MHz in C 6 D 6 and in CDCl 3 of the divalent cation ionophore A23187 and its magnesium salt are reported and discussed in terms of configurational and conformational behaviour. The conformation of the free acid in solution was found to be almost identical to that described previously (M. O. Chaney, P. V. Demarco, N. D. Jones, and J. L. Occolowitz, J. Amer. Chem. Soc. 96 , 1932 (1974)) for the solid state, except that in apolar solvents no head-to-tail interaction is observed, in that free rotation around certain bonds (e.g., C 15 –C 19 , structures 1 and 2 ) substantially prevents such quasi-cyclic forms. For the conformation of the magnesium salt, two monovalent units aggregate around the divalent cation, the two substructures displaying equivalent atoms in each of their corresponding positions. A compact sphere-like form having a C 2 axis and a cavity of about 3.5 A is proposed, the cation being held in the middle by two carboxylate ions, carbonyl and N -benzoxazole units as the ligands. These conclusions result from consideration of the extracted parameters in the proton nmr spectrum and from model building. Thus, the most probable form of the Mg-salt in solution corresponds almost exactly to that of the Ca-salt in the solid state, as very recently revealed by the X-ray analysis of M. O. Chaney, N. D. Jones, and M. Debono ( J. Antibiot , in press).

Solution conformation of lasalocid and lasalocid-Na+ (X-537A)

Abstract The complete unraveling of the proton nuclear magnetic resonance spectra at high field strength of Lasalocid ( 1 ) and its sodium salt ( 2 ) in different solvents allowed the definition of their solution conformations. The free acid, a lozengeshaped molecule of 17 × 13 × 9 A is prefolded in a way almost identical to that of its sodium derivative, where the ion lies in the centre, surrounded by all the oxygen atoms in the molecule except for the phenolic one. Although the upper side of the molecule is rather accessible to hydrophilic approach, some alkyl substituents are arranged out- and upwards, thus shielding the ion from possible contact with lipophilic surroundings. The spatial picture suggests that the ion is trapped upon arrival at one side (the flat upper side) and is released either at the same or at the opposite side.

1′,2′-Dideacetylboronolide, an α-pyrone from Iboza riparia

The structural elucidation of 1′,2′-dideacetylboronolide, 5,6-dihydro-6-(3′-acetoxy-1′,2′-dihydroxyheptyl)2-pyrone, a new α-pyrone isolated from the leaves of Iboza riparia has been performed. Additionally, three sterols, sitosterol, stigmasterol and campesterol, have been identified in this species.

Configurational assignment and 1H-NMR spectral parameters of the isomeric 1,4-diacetoxy-2,3-dimethylcyclopentanes

Abstract All six 1,4-diacetoxy-2,3-dimethyl-cyclopentanes have been prepared starting from 2, 3-dimethyl-4-hydroxy-2-cyclopentenone. 1 H-NMR spectral parameters, allowing configurational assignment, are discussed.

Selective Removal of the Isopropylidene Group in 4-O-Protected 1,6-Anhydro-2,3-O-Isopropylidene-β-D-Mannopyranose and the Conformational Impact of it

Abstract Pyridinium p-toluenesulfonate (PPTS) is a reagent of choice for the selective removal of an O-isopropylidene group in a 1,6-anhydro-β-d-aldohexopyranose, where the remaining OH-group is protected.

High field 1H NMR studies. Influence of the cis/trans isomerism on the N-acetyl 4-hydroxy proline ring conformation

Abstract Complete analysis of the high resolution NMR spectra of N-acetyl 4-hydroxy Proline (AcOH-PRO) has been made and it is shown that conformational cyclic changes may be explained in terms of cis/trans isomerism of the N-Acetyl group. In extension it is suggested that the greater stabilities of the trans forms of poly(PRO) and poly(OH-PRO) as well as many proline-containing peptides and polymers may be explained in terms of restricted orientation of the C-4 carbon atoms.

Solution conformation of Monensin free acid, a typical representative of the polyetherin antibiotics

Abstract The solution conformation of the ionophore Monensin in its free-acid form bears a close resemblance to that of its Na + salt. The backbone is folded into a closed loop, and the pseudocyclic structure is shut by head-to-tail H bonding between the carboxylic function and the alcoholic functions of the last six-membered ring with the mediation of a water molecule. A mode of trapping is proposed and compared to features observed in some other membrane-active complexones.