191655-44-4Relevant academic research and scientific papers
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
De novo synthesis, structural assignment and biological evaluation of pseudopaline, a metallophore produced by Pseudomonas aeruginosa
Zhang, Jian,Zhao, Tianhu,Yang, Rongwen,Siridechakorn, Ittipon,Wang, Sanshan,Guo, Qianqian,Bai, Yingjie,Shen, Hong C.,Lei, Xiaoguang
, p. 6635 - 6641 (2019)
Pseudopaline is an opine carboxylate metallophore produced by Pseudomonas aeruginosa for harvesting divalent metals. However, the structure of pseudopaline is not fully elucidated. Herein, we report the first de novo total synthesis and isolation of pseudopaline, which allows unambiguous determination and confirmation of both the absolute and the relative configuration of the natural product. The synthesis highlights an efficient and stereocontrolled route using the asymmetric Tsuji-Trost reaction as the key step. The preliminary structure-activity relationship study indicated that one pseudopaline derivative shows comparable activity to pseudopaline. Moreover, a pseudopaline-fluorescein conjugate was prepared and evaluated, which confirmed that pseudopaline could be transported in the bacteria. Since the metal acquisition by P. aeruginosa is crucial for its ability to cause diseases, our extensive structural and functional studies of pseudopaline may pave the way for developing new therapeutic strategies such as the "Trojan horse" antibiotic conjugate against P. aeruginosa.
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.
Pseudomonas aeruginosa metabolite and its derivative, and synthetic method and application thereof
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Paragraph 0077-0079, (2020/01/12)
The invention relates to a Pseudomonas aeruginosa metabolite and a derivative thereof. The structural general formula of the metabolite is represented by formula I. The Pseudomonas aeruginosa metabolite and its derivative have a specific stereoconfigurati
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.
