3845-64-5Relevant articles and documents
Synthesis and X-ray Structure of the Chiral, Polydentate Cation Binder N--L-methionyl>histamine
Modder, Johan F.,Vrieze, Kees,Spek, Anthony L.,Koten, Gerard van
, p. 5606 - 5610 (1991)
A synthetic route has been developed to obtain N--L-methionyl>histamine, optically pure (α20 = -8.13 deg/L mol-1 dm-1), from a sequence of reactions involving L-methionine, histamine, and 5-methyl-2-thiophenecarbaldehyde.The described procedure affords gram quantities in an overall yield of 40percent, without the need of any chromatographic techniques.Moreover, the removal of the well-known tert-butyloxycarbonyl amino-protection group (BOC) with gaseous hydrochloric acid, in the present synthesis, had considerable advantages compared with the commonly applied trifluoroacetic acid method.The structure of N--L-methionyl>histamine in the solid has been determined by X-ray diffraction techniques.C16H22N4OS2 crystallizes in the monoclinic space group P21, with a = 5.233(1), b = 9.556(1), and c = 17.919(1) Angstroem; β = 98.32(1) deg; and Z = 2.Noteworthy aspects of the tertiary structure of the molecule are the fact that it is almost flat, the three arms connected to methionine-Ca, being the (thienylmethylidene)amino moiety, the "imidazole-amide" fragment, and the methionine side chain, spread out. ?-Conjugation causes the (thienylmethylidene)amino moiety to have a planar s-cis conformation, and the methionine side chain's all-trans conformation is due to vicinal interactions.The gauche conformation of the "imidazole-amide" does not have a clear origin, but is no artifact of the solid state.Intra- and intermolecular hydrogen bonds are prominently present, the former determining the relative orientations of the aforementioned arms and the latter linking the title molecules into two-dimensional, sheetlike entities.
DIPEPTIDE MIMETICS OF NGF AND BDNF NEUROTROPHINS
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Paragraph 0188, (2019/04/16)
The invention relates to compounds having either agonist or antagonist activities for the neurotrophins NGF and BDNF and represented by monomeric or dimeric substituted dipeptides that are analogs of the exposed portions of loop 1 or loop 4 regions of these neurotrophins near or at a beta-turn of the respective loop. N-acylated substituents of these dipeptides are biostereoisomers of the amino acid residues preceding these dipeptide sequences in the neurotrophin primary structure. The dimeric structure is produced advantageously by using hexatnethylenediaanine to which dipeptides are attached via their carboxyl groups. The claimed compounds displayed neuroprotective and differentiation-inducing activities in cellular models and enhanced the amount of phosphorylated tyrosine kinase A and the heat shock proteins Hsp32 and Hsp70 in the concentration range of 10 -9 to 10 -5 M. They also displayed neuroprotective, anti-parkinsonian, anti-stroke, anti-ischemic, anti-depressant and anti-amnestic activities in animal models and were active in experimental models of Alzheimer's disease. These in vivo effects of the claimed compounds are displayed in the dose range of 0.01 to 10 mg/kg when administered intraperitoneally.
Solventless mechanosynthesis of N-protected amino esters
Konnert, Laure,Lamaty, Frederic,Martinez, Jean,Colacino, Evelina
, p. 4008 - 4017 (2014/05/20)
Mechanochemical derivatizations of N- or C-protected amino acids were performed in a ball mill under solvent-free conditions. A vibrational ball mill was used for the preparation of N-protected α- and β-amino esters starting from the corresponding N-unmasked precursors via a carbamoylation reaction in the presence of di-tert-butyl dicarbonate (Boc2O), benzyl chloroformate (Z-Cl) or 9-fluorenylmethoxycarbonyl chloroformate (Fmoc-Cl). A planetary ball mill proved to be more suitable for the synthesis of amino esters from N-protected amino acids via a one-pot activation/esterification reaction in the presence of various dialkyl dicarbonates or chloroformates. The spot-to-spot reactions were straightforward, leading to the final products in reduced reaction times with improved yields and simplified work-up procedures.