497830-99-6Relevant 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.
Efficient synthesis of N-protected amino/peptide Weinreb amides from T3P and DBU
Sharnabai,Nagendra,Vishwanatha,Sureshbabu, Vommina V.
, p. 478 - 482 (2013/02/23)
The reaction of Nα-protected amino/peptide acid with N,O-dimethylhydroxylamine hydrochloride in the presence of T3P and DBU to obtain enantiomerically pure Nα-protected amino/peptidyl Weinreb amides in high yields has been described. Fmoc-Ala-Weinreb amide 2a is obtained as single crystal, and its structure was determined through X-ray crystallography.
Peptide fragment coupling using a continuous-flow photochemical rearrangement of nitrones
Zhang, Yuan,Blackman, Melissa L.,Leduc, Andrew B.,Jamison, Timothy F.
supporting information, p. 4251 - 4255 (2013/05/08)
Go with the flow: A general approach for amide bond formation by way of a continuous-flow photochemical rearrangement of nitrones was described (see scheme). Simple aryl-alkyl amide bonds as well as complex peptide bonds were constructed efficiently with a residence time less than 20minutes. A tetrapeptide was synthesized in this way and the method could be applied to peptide fragment coupling. Copyright
Synthesis of densely functionalized pyrrolidinone templates by an intramolecular oxo-Diels-Alder reaction
Murray, William V.,Mishra, Pranab K.,Sun, Sengen,Maden, Amy
, p. 7389 - 7392 (2007/10/03)
Preparation of densely functionalized pyrrolidinone templates, is a challenge for synthetic chemists. These templates are important building blocks for novel conformationally constrained natural products or for library generation of highly functionalized
