Peter Kremminger

ASYMMETRIC SYNTHESIS OF UNSATURATED AND BIS-HYDROXYLATED (S,S)-2,7-DIAMINOSUBERIC ACID DERIVATIVES.

Abstract Stereoselective syntheses of cystine substitutes with all-carbon C4-bridges are described. The disulfide unit between the two alanine moieties in cystine has been replaced by a C2-unit. When the C2-unit is olefinic, conformationally constrained cis- and trans-unsaturated analogues result. Vicinal dihydroxy analogues were formed when the C2-unit was a vicinal 1,2-ethylenediol derivative. N-Fmoc protection of the new C4-bridged bis(amino acids) is described.

Hydrophobic forms of morphine-6-glucosides

NMR spectroscopy of 6-acetylmorphine (6-AM), a chloroform-soluble model compound for the hydrophilic, highly potent analgesic drug morphine-6-glucoronide (M6G), in a hydrophobic solvent indicates one hydrogen bonded water molecule per molecule of 6-AM. By analysis of nuclear Overhauser enhancements (NOEs) we find a 6-AM dimer in which the monomers are linked by two water molecules. Molecular modeling studies underscore the stability of such dimeric structures involving water molecules for 6-AM and point out their more lipophilic character allowing penetration of the blood-brain barrier.

Synthesis of orthogonally protected hydroxylated azalkene-α,α′-bridged bis(α-glycine) and dihydroxylysine derivatives

Abstract Stereoselective syntheses of hydroxylated azalkene-α,α′- bridged bis(α-glycine) derivatives and lysine derivatives are described. The bridge was formed as a secondary amine by a reductive dimerization process of two azide molecules upon hydrogenolysis over 5% palladium-on-charcoal. Lysine derivatives were formed by reduction of the azide function to a primary amine. In the target amino acids the vicinal dihydroxy functions were protected as acetonides, the N ′-amino group as a Z-derivative and the α-amino groups as Fmoc-derivatives.

THE CRYSTAL STRUCTURE OF N, N'-BIS-(1,3-DIHYDROXY-2-METHYLPROP-2-YL)-PYRAZINE-2,3-DICARBOXAMIDE SEMIHYDRATE

Crystals of the title compound were obtained by recrystallization of N,N′-bis-( 1,3-dihydroxy- 2-methylprop-2-yl)-pyrazine-2,3-dicarboxamide in aqueous methanol. C14H22N4O6 · 1/2H2O crystallizes in the triclinic system, s.g. P1̄ (No. 2) with a = 9.339(4) Å, b = 13.218(9) Å, c = 14.5137(9) Å, α = 70.95(4)°, β = 87.66(4)°, ɣ = 87.13(4)°, Z = 4. Its crystal structure has been determined from diffractometer data and refined to a conventional R of 0.050 (4008 observations, 464 variable parameters). The structure contains two crystallographically independent molecules which are alternatingly stacked above each other along the [001]-direction. Extensive intermolecular hydrogen bonding between these stacks leads to the formation of slabs parallel to (010). The hydrate water is only loosely attached to one of the molecules and has no apparent influence on the stacking.