26061-06-3Relevant articles and documents
Synthesis and Structure-Activity Relationships of Ring-Opened Bengamide Analogues against Methicillin-Resistant Staphylococcus aureus?
Yu, Chen-Xi,Wei, Bing-Yan,Kong, Xue-Qing,Yang, Cai-Guang,Nan, Fa-Jun
supporting information, p. 671 - 676 (2021/02/12)
Methicillin-resistant Staphylococcus aureus (MRSA) has become a major threat on public health because of the increase of clinically isolated strains that exhibit resistance to many antibiotics. Therefore, development of new antibiotics for the treatment of MRSA infection is a sustained challenge. We have previously identified a ring-opened bengamide analogue L472-2 that displays moderate activity against the growth of S. aureus. In our previous work, we started from L472-2 and identified a class of analogues containing alkynyl groups which have the potential to activate SaClpP activity but moderate antibacterial activity. Herein, we focused on the antibacterial activity of L472-2, and a novel series of ring-opened bengamide analogues were synthesized and their activities were evaluated against MRSA. By conducting a compact analysis of the structure-activity relationships (SAR) of these analogues, we found that an adamantane ethanol ester bengamide 2j showed excellent antibacterial activity towards six S. aureus strains, including MRSA, while it does not activate ClpP. Therefore, these bengamide analogues represent a new class of candidates that suppress MRSA viability.
Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis
Siebert, David C.B.,Sommer, Roman,Pogorevc, Domen,Hoffmann, Michael,Wenzel, Silke C.,Müller, Rolf,Titz, Alexander
supporting information, p. 2922 - 2929 (2019/12/23)
The argyrins are secondary metabolites from myxobacteria with antibiotic activity against Pseudomonas aeruginosa. Studying their structure–activity relationship is hampered by the complexity of the chemical total synthesis. Mutasynthesis is a promising approach where simpler and fully synthetic intermediates of the natural product’s biosynthesis can be biotechnologically incorporated. Here, we report the synthesis of a series of tripeptide thioesters as mutasynthons containing the native sequence with a dehydroalanine (Dha) Michael acceptor attached to a sarcosine (Sar) and derivatives. Chemical synthesis of the native sequence D-Ala-Dha-Sar thioester required revision of the sequential peptide synthesis into a convergent strategy where the thioester with sarcosine was formed before coupling to the Dha-containing dipeptide.
Copper(I)-Mediated Denitrogenative Macrocyclization for the Synthesis of Cyclic α3β-Tetrapeptide Analogues
Chen, Chun-Chi,Wang, Sheng-Fu,Su, Yung-Yu,Lin, Yuya A.,Lin, Po-Chiao
, p. 1326 - 1337 (2017/06/23)
A copper(I)-mediated denitrogenative reaction has been successfully developed for the preparation of cyclic tetrapeptides. The key reactive intermediate, ketenimine, triggers intramolecular cyclization through attack of the terminal amine group to generate an internal β-amino acid with an amidine linkage. The chemistry developed herein provides a new synthetic route for the preparation of cyclic α3β-tetrapeptide analogues that contain important biological properties and results in rich structural information being obtained for conformational studies. With the success of this copper(I)-catalyzed macrocyclization, two histone deacetylase inhibitor analogues consisting of the cyclic α3β-tetrapeptide framework have been successfully synthesized.
