4351-11-5Relevant articles and documents
Discovery of 2-Sulfinyl-Diazabicyclooctane Derivatives, Potential Oral β-Lactamase Inhibitors for Infections Caused by Serine β-Lactamase-Producing Enterobacterales
Fujiu, Motohiro,Yokoo, Katsuki,Sato, Jun,Shibuya, Satoru,Komano, Kazuo,Kusano, Hiroki,Sato, Soichiro,Aoki, Toshiaki,Kohira, Naoki,Kanazawa, Sachi,Watari, Ryosuke,Kawachi, Tomoyuki,Hirakawa, Yuya,Nagamatsu, Daiki,Kashiwagi, Emi,Maki, Hideki,Yamawaki, Kenji
supporting information, p. 9496 - 9512 (2021/07/19)
Coadministration of β-lactam and β-lactamase inhibitor (BLI) is one of the well-established therapeutic measures for bacterial infections caused by β-lactam-resistant Gram-negative bacteria, whereas we have only two options for orally active BLI, clavulanic acid and sulbactam. Furthermore, these BLIs are losing their clinical usefulness because of the spread of new β-lactamases, including extended-spectrum β-lactamases (ESBLs) belonging to class A β-lactamases, class C and D β-lactamases, and carbapenemases, which are hardly or not inhibited by these classical BLIs. From the viewpoints of medical cost and burden of healthcare personnel, oral therapy offers many advantages. In our search for novel diazabicyclooctane (DBO) BLIs possessing a thio-functional group at the C2 position, we discovered a 2-sulfinyl-DBO derivative (2), which restores the antibacterial activities of an orally available third-generation cephalosporin, ceftibuten (CTB), against various serine β-lactamase-producing strains including carbapenem-resistant Enterobacteriaceae (CRE). It can be orally absorbed via the ester prodrug modification and exhibits in vivo efficacy in a combination with CTB.
Design, Synthesis, and Preliminary Immunological Studies of MUC1-Based Antitumor Vaccines Adjuvanted with R- And S-FSL-1
Liu, Yonghui,Yan, Bocheng,Wang, Zhaoyu,Zhu, Haomiao,Yin, Xiaona,Wang, Kun,Wang, Menglei,Zhao, Wei
supporting information, p. 1371 - 1376 (2020/07/31)
Fibroblast stimulating lipopeptide 1 (FSL-1) is the ligand of TLR2 and TLR6 and can be used as the vaccine adjuvant to prepare antitumor vaccines. However, FSL-1 is a stereoisomeric mixture that contains the R stereoisomer and S stereoisomer, and it is still unclear which stereoisomer has better adjuvant activities. In this work, we designed and synthesized MUC1-based antitumor vaccines adjuvanted with the stereoisomers R-FSL-1 and S-FSL-1, which were synthesized from the stereoisomeric building blocks R-Fmoc-Pam2Cys-OH and S-Fmoc-Pam2Cys-OH, respectively. Immunological evaluation indicated that both R-FSL-1 and S-FSL-1 can be used as adjuvants for the construction of MUC1-based antitumor vaccines, with R-FSL-1 showing a better adjuvant effect than S-FSL-1.
An efficient and scalable synthesis of potent TLR2 agonistic PAM2CSK4
Kaur, Arshpreet,Poonam,Patil, Madhuri T.,Mehta, Surinder K.,Salunke, Deepak B.
, p. 9587 - 9596 (2018/03/23)
Diacylated PAM2CSK4, a highly expensive lipopeptide with desirable aqueous solubility and a broad spectrum of cytokine/chemokine induction is a most potent dual (human and murine) Toll-Like Receptor-2 (TLR2) agonist. Besides such thrilling characteristics, its synthetic process is not reported in the literature. The present report describes an efficient and scalable 20 step synthesis of PAM2CSK4 in good yield (all steps > 60%) along with a clear description of the hindrances and easy solutions adopted in each step. Overall, a convergent synthetic approach was adopted involving synthesis of appropriately protected starting materials, synthesis of a key backbone skeleton PAM2CS, synthesis of a tetralysine fragment and the final coupling to yield PAM2CSK4. Tedious column chromatography was avoided on a large scale in many steps.
