Johann Hiebl

A detailed investigation of the preparation of 2,7-diaminosuberic acid and 2,5-diaminoadipic acid derivatives using Kolbe electrolysis

Abstract The yield of protected 2,7- diaminosuberic acid (DAS) prepared by Kolbe reaction of N-protected α-glutamic acid esters is dependent on solvent, temperature, concentration of carboxylate anion, and protecting groups. The highest yield of protected L,L-2,7-diaminosuberic acid is obtained with Boc-Glu-OMe as starting material using MeOH/pyridine/NaOMe as electrolyte.

One step synthesis of orthogonally protected diaminodicarboxylic acids by mixed kolbe electrolysis

Abstract Orthogonally protected 2,5-diaminoadipic, 2,6-diaminopimelic, and 2,7-diaminosuberic acid derivatives bearing up to four different protecting groups are prepared in one step by mixed Kolbe electrolysis. The use of 2-[(4-methylphenyl)sulfonyl]ethyl group is crucial for the isolation of the desired orthogonally protected products.

THE CRYSTAL STRUCTURE OF DIMETHYL (2Z, 6Z)-2,7-BIS-(BENZYLOXYCARBONYLAMINO)OCTA-2,6-DIENDIOATE : A USEFUL PRECURSOR FOR OPTICALLY PURE 2,7-DIAMINOSUBE RIC ACID

Needle shaped single crystals of the dimethyl ester of (2Z, 6Z)-2,7-bis-(benzyloxycarbonylamino)- octa-2,6-diendioic acid (1), C26H28N2O8 were obtained by very slow cooling from methanol/ethylacetate solution 20:1. 1 crystallizes in the anorthic space group Pl̅ (No.2) with a = 4.813(5), b = 12.277(6), c = 12.340(7) Å, α =117.15(3)°, β = 97.52(4)°, γ = 92.02(4)°, Z =1. The crystal structure was determined from diffractometer data (MoKα-radiation). It was solved by direct methods and refined to a conventional R of 0.054 for 1452 Fos and 178 refined parameters. The molecule is characterized by the presence of an inversion center. In the crystal structure the molecules are stacked along the crystallographic a-axis. In this direction - which coincides with the needle axis of the crystals - each molecule is connected with its neighbors through almost linear N-H···O-hydrogen bonds.

A pharmacophore model of a hematoregulatory peptide, SK&F 107647 and design of peptidomimetic analogs

P. K. Bhatnagar, E. K. Agner, D. Alberts, J. Briand, J. F. Callahan, A. S. Cuthbertson, H. Fjerdingstad, D. Heerding, J. Hiebl, W. F. Huffman, M. Husbyn, A. G. King, S. LoCastro, D. Lovhaug, L. M. Pelus, G. Seibel and J. S. Takata a Departments of Medicinal Chemistry and b Molecular Virology and Host Defense, SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, P.O. Box 1539, King of Prussia, PA 19206, USA, Nycomed Pharma As, Gaustadalleene 21, Oslo, Norway, Hafslund Nycomed Pharma, St. Peter-Strasse 25, P.O. Box 120, A-2021 Linz, Austria

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.