269733-21-3Relevant academic research and scientific papers
Macrocyclic BACE1 inhibitors with hydrophobic cross-linked structures: Optimization of ring size and ring structure
Otani, Takuya,Hattori, Yasunao,Akaji, Kenichi,Kobayashi, Kazuya
, (2021/11/22)
Based on the X-ray crystallography of recombinant BACE1 and a hydroxyethylamine-type peptidic inhibitor, we introduced a cross-linked structure between the P1 and P3 side chains of the inhibitor to enhance its inhibitory activity. The P1 and P3 fragments bearing terminal alkenes were synthesized, and a ring-closing metathesis of these alkenes was used to construct the cross-linked structure. Evaluation of ring size using P1 and P3 fragments with various side chain lengths revealed that 13-membered rings were optimal, although their activity was reduced compared to that of the parent compound. Furthermore, the optimal ring structure was found to be a macrocycle with a dimethyl branched substituent at the P3 β-position, which was approximately 100-fold more active than the non-substituted macrocycle. In addition, the introduction of a 4-carboxymethylphenyl group at the P1′ position further improved the activity.
Asymmetric synthesis of differentially protected meso-2,6-diaminopimelic acid
Roberts, John L.,Chan, Cecil
, p. 7679 - 7682 (2007/10/03)
meso-2,6-Diaminopimelic acid, an important linking component of bacterial cell walls and a biosynthetic precursor of L-lysine has been prepared differentially protected in a stereospecific manner from both L-aspartic and L-glutamic acid. The key step to establish the second chiral center involves the asymmetric reduction of a pyruvate moiety with Alpine-Borane. S-2-Amino-6-oxopimelic acid, the hydrolyzed open chain form of tetrahydrodipicolinic acid, a biosynthetic precursor of meso-2,6-diaminopimelic acid, was also prepared via deprotection of the key pyruvate intermediate.
The efficient, enantioselective synthesis of quinoxaline, pyrazine and 1,2,4-triazine substituted α-amino acids from vicinal tricarbonyls
Adlington,Baldwin,Catterick,Pritchard
, p. 668 - 679 (2007/10/03)
The reaction of diamines and amidrazones with α-amino acid vicinal tricarbonyls has been shown to be a versatile route towards novel heterocyclic α-amino acids. This route is also applicable to parallel synthesis and has allowed the formation of a range o
A versatile synthetic route to quinoxaline, pyrazine and 1,2,4-triazine substituted α-amino acids from vicinal tricarbonyls
Adlington, Robert M.,Baldwin, Jack E.,Catterick, David,Pritchard, Gareth J.
, p. 299 - 302 (2007/10/03)
A range of novel heterocyclic α-amino acids has been synthesised by the reaction of diamines and amidrazones with α-amino acid vicinal tricarbonyl reactive substrates. The Royal Society of Chemistry 2000.
