26973-43-3Relevant academic research and scientific papers
Identification and Profiling of a Novel Diazaspiro[3.4]octane Chemical Series Active against Multiple Stages of the Human Malaria Parasite Plasmodium falciparum and Optimization Efforts
Le Manach, Claire,Dam, Jean,Woodland, John G.,Kaur, Gurminder,Khonde, Lutete P.,Brunschwig, Christel,Njoroge, Mathew,Wicht, Kathryn J.,Horatscheck, André,Paquet, Tanya,Boyle, Grant A.,Gibhard, Liezl,Taylor, Dale,Lawrence, Nina,Yeo, Tomas,Mok, Sachel,Eastman, Richard T.,Dorjsuren, Dorjbal,Talley, Daniel C.,Guo, Hui,Simeonov, Anton,Reader, Janette,Van Der Watt, Mari?tte,Erlank, Erica,Venter, Nelius,Zawada, Jacek W.,Aswat, Ayesha,Nardini, Luisa,Coetzer, Theresa L.,Lauterbach, Sonja B.,Bezuidenhout, Belinda C.,Theron, Anjo,Mancama, Dalu,Koekemoer, Lizette L.,Birkholtz, Lyn-Marie,Wittlin, Sergio,Delves, Michael,Ottilie, Sabine,Winzeler, Elizabeth A.,Smith, Dennis,Fidock, David A.,Street, Leslie J.,Basarab, Gregory S.,Duffy, James,Chibale, Kelly
supporting information, p. 2291 - 2309 (2021/03/01)
A novel diazaspiro[3.4]octane series was identified from a Plasmodium falciparum whole-cell high-throughput screening campaign. Hits displayed activity against multiple stages of the parasite lifecycle, which together with a novel sp3-rich scaffold provided an attractive starting point for a hit-to-lead medicinal chemistry optimization and biological profiling program. Structure-activity-relationship studies led to the identification of compounds that showed low nanomolar asexual blood-stage activity (50 nM) together with strong gametocyte sterilizing properties that translated to transmission-blocking activity in the standard membrane feeding assay. Mechanistic studies through resistance selection with one of the analogues followed by whole-genome sequencing implicated the P. falciparum cyclic amine resistance locus in the mode of resistance.
Next-Generation Total Synthesis of Vancomycin
Boger, Dale L.,Cai, Yu,Jamin Keith, D.,Mogi, Yuzo,Moore, Maxwell J.,Qu, Shiwei,Tan, Ceheng
supporting information, p. 16039 - 16050 (2020/10/02)
A next-generation total synthesis of vancomycin aglycon is detailed that was achieved in 17 steps (longest linear sequence, LLS) from the constituent amino acid subunits with kinetically controlled diastereoselective introduction of all three elements of atropisomerism. In addition to new syntheses of three of the seven amino acid subunits, highlights of the approach include a ligand-controlled atroposelective one-pot Miyaura borylation-Suzuki coupling sequence for introduction of the AB biaryl axis of chirality (>20:1 dr), an essentially instantaneous and scalable macrolactamization of the AB ring system nearly free of competitive epimerization (>30:1 dr), and two room-temperature atroposelective intramolecular SNAr cyclizations for sequential CD (8:1 dr) and DE ring closures (14:1 dr) that benefit from both preorganization by the preformed AB ring system and subtle substituent effects. Combined with a protecting group free two-step enzymatic glycosylation of vancomycin aglycon, this provides a 19-step total synthesis of vancomycin. The approach paves the way for large-scale synthetic preparation of pocket-modified vancomycin analogues that directly address the underlying mechanism of resistance to vancomycin.
Synthesis of linear tripeptides for right-hand segments of complestatin
Yamada, Yaeko,Akiba, Ai,Arima, Shiho,Okada, Chiharu,Yoshida, Kiminari,Itou, Fumihiro,Kai, Toshitsugu,Satou, Toshiko,Takeda, Kazuyoshi,Harigaya, Yoshihiro
, p. 1277 - 1290 (2007/10/03)
This paper concerns a synthetic study of the right-hand segment of complestatin, an inhibitor of gp120-CD4 receptor. The effective synthesis of four important precursors for the right-hand segment of complestatin is described. Two of them are the precurso
Complestatin synthetic studies: The effect of the amino acid configuration on peptide backbone conformation in the common western BCD macrocycle
Smith III, Amos B.,Chruma, Jason J.,Han, Qiang,Barbosa, Joseph
, p. 1697 - 1702 (2007/10/03)
The synthesis and structural analysis, involving X-ray crystallographic, nuclear magnetic resonance, and computational studies of four diastereomers of the common western BCD diarylether macrocycle of the complestatins, a family of HIV entry inhibitors, h
Macrocyclization by TTN Oxidation for the Synthesis of Chloropeptin Left-Hand Segment
Kai, Toshitsugu,Kajimoto, Naoko,Konda, Yaeko,Harigaya, Yoshihiro,Takayanagi, Hiroaki
, p. 6289 - 6292 (2007/10/03)
Cyclic tripeptide containing a diphenylether bond of the Chloropeptin left-hand segment were synthesized with the use of TTN phenolic oxidation in high yield. They were found to exist as equilibrium mixtures of two stable conformers caused by a rotation o
