191655-44-4Relevant articles and documents
A general strategy for the synthesis of azapeptidomimetic lactams
Broadrup, Robert L.,Wang, Bei,Malachowski, William P.
, p. 10277 - 10284 (2005)
A selection of azapeptidomimetics containing constraining lactam rings have been prepared by Mitsunobu cyclization of serine/homologated serine-azaalanine derivatives. These include sterically-congested β-lactams, as well as γ-butyrolactam and δ-valerolac
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.
Polyamide based nucleic acid analogs synthesis of δ-amino acids with nucleic acid bases bearing side chains
Altmann, Karl-Heinz,Chiesi, Chantal Schmit,Garcia-Echeverria, Carlos
, p. 1119 - 1122 (2007/10/03)
Nucleoamino acids of type I-III have been synthesized, which can serve as building blocks for novel polyamide based nucleic acid analogs. Key steps in the syntheses are the alkylation of serinol I and homoserinol 18 with tert-butyl bromoacetate or tert-butyl bromopropionate under phase transfer conditions and the introduction of thymine or uracil into the amino acid side drains by way of a Mitsunobu reaction. Cytosine derivatives were prepared through uracil → cytosine base conversion at the stage of N(δ)-BOC protected amino acid tert-butyl esters.
