Home
  >  
Section 60
  >  
Chapter 59,679

Enantioselective Total Synthesis of Antibiotic CJ-16,264, Synthesis and Biological Evaluation of Designed Analogues, and Discovery of Highly Potent and Simpler Antibacterial Agents

Nicolaou, K.C.; Pulukuri, K.Kumar.; Rigol, S.; Buchman, M.; Shah, A.A.; Cen, N.; McCurry, M.D.; Beabout, K.; Shamoo, Y.

Journal of the American Chemical Society 139(44): 15868-15877

2017

ISSN/ISBN: 0002-7863
PMID: 29064688
DOI: 10.1021/jacs.7b08749
Accession: 059678447
An improved and enantioselective total synthesis of antibiotic CJ-16,264 through a practical kinetic resolution and an iodolactonization reaction to form the iodo pyrrolizidinone fragment of the molecule is described. A series of racemic and enantiopure analogues of CJ-16,264 was designed and synthesized through the developed synthetic technologies and tested against drug-resistant bacterial strains. These studies led to interesting structure-activity relationships and the identification of a number of simpler, and yet equipotent, or even more potent, antibacterial agents than the natural product, thereby setting the foundation for further investigations in the quest for new anti-infective drugs.

PDF emailed within 0-6 h: $19.90




Related References

Nicolaou, K.C.; Chen, P.; Zhu, S.; Cai, Q.; Erande, R.D.; Li, R.; Sun, H.; Pulukuri, K.Kumar.; Rigol, S.; Aujay, M.; Sandoval, J.; Gavrilyuk, J. 2017: Streamlined Total Synthesis of Trioxacarcins and Its Application to the Design, Synthesis, and Biological Evaluation of Analogues Thereof. Discovery of Simpler Designed and Potent Trioxacarcin Analogues Journal of the American Chemical Society 139(43): 15467-15478
Nicolaou, K.C.; Rhoades, D.; Kumar, S.Mothish. 2018: Total Syntheses of Thailanstatins A-C, Spliceostatin D, and Analogues Thereof. Stereodivergent Synthesis of Tetrasubstituted Dihydro- and Tetrahydropyrans and Design, Synthesis, Biological Evaluation, and Discovery of Potent Antitumor Agents Journal of the American Chemical Society 140(26): 8303-8320
Nicolaou, K.C.; Liu, G.; Beabout, K.; McCurry, M.D.; Shamoo, Y. 2017: Asymmetric Alkylation of Anthrones, Enantioselective Total Synthesis of (-)- and (+)-Viridicatumtoxins B and Analogues Thereof: Absolute Configuration and Potent Antibacterial Agents Journal of the American Chemical Society 139(10): 3736-3746
Nicolaou, K.C.; Lu, M.; Totokotsopoulos, S.; Heretsch, P.; Giguère, D.; Sun, Y-Ping.; Sarlah, D.; Nguyen, T.H.; Wolf, I.C.; Smee, D.F.; Day, C.W.; Bopp, S.; Winzeler, E.A. 2012: Synthesis and biological evaluation of epidithio-, epitetrathio-, and bis-(methylthio)diketopiperazines: synthetic methodology, enantioselective total synthesis of epicoccin G, 8,8'-epi-ent-rostratin B, gliotoxin, gliotoxin G, emethallicin E, and haematocin and discovery of new antiviral and antimalarial agents Journal of the American Chemical Society 134(41): 17320-17332
Hunault, J.; Diswall, M.; Frison, J.-C.éd.; Blot, V.; Rocher, J.éz.; Marionneau-Lambot, S.év.; Oullier, T.; Douillard, J.-Y.; Guillarme, S.ép.; Saluzzo, C.; Dujardin, G.; Jacquemin, D.; Graton, J.ér.ôm.; Le Questel, J.-Y.; Evain, M.; Lebreton, J.; Dubreuil, D.; Le Pendu, J.; Pipelier, M. 2012: 3-fluoro- and 3,3-difluoro-3,4-dideoxy-KRN7000 analogues as new potent immunostimulator agents: total synthesis and biological evaluation in human invariant natural killer T cells and mice Journal of Medicinal Chemistry 55(3): 1227-1241
Altmann, K.H.; Bold, G.; Caravatti, G.; Flörsheimer, A.; Guagnano, V.; Wartmann, M. 2000: Synthesis and biological evaluation of highly potent analogues of epothilones B and D Bioorganic and Medicinal Chemistry Letters 10(24): 2765-2768
Altmann, K.H.; Bold, G.; Caravatti, G.; Florsheimer, A.; Guagnano, V.; Wartmann, M. 2000: Synthesis and biological evaluation of highly potent analogues of epothilones B and D Bioorganic and Medicinal Chemistry Letters 10(24): 2765-2768, 18 December
Wang, X.; Nakagawa-Goto, K.; Bastow, K.F.; Don, M-Jaw.; Lin, Y-Lian.; Wu, T-Shung.; Lee, K-Hsiung. 2006: Antitumor agents. 254. Synthesis and biological evaluation of novel neo-tanshinlactone analogues as potent anti-breast cancer agents Journal of Medicinal Chemistry 49(18): 5631-5634
Suresh Babu, K.; Hari Babu, T.; Srinivas, P.V.; Hara Kishore, K.; Murthy, U.S.N.; Rao, J.M. 2006: Synthesis and biological evaluation of novel C (7) modified chrysin analogues as antibacterial agents Bioorganic and Medicinal Chemistry Letters 16(1): 221-224
Jiang, X.; Wang, Y.; Zhang, G.; Fu, D.; Zhang, F.; Kai, M.; Wang, R. 2011: Enantioselective Synthesis of Cyclic Thioureas via Mannich Reaction and Concise Synthesis of Highly Optically Active Methylthioimidazolines: Discovery of a more Potent Antipyretic Agent Advanced Synthesis and Catalysis 353(10): 1787-1796
Wang, L.; Xie, S.; Ma, L.; Chen, Y.; Lu, W. 2015: Design, synthesis and biological evaluation of novel homocamptothecin analogues as potent antitumor agents Bioorganic and Medicinal Chemistry 23(9): 1950-1962
Nevagi, R.J.; Dhake, A.S.; Narkhede, H.I.; Kaur, P. 2014: Design, synthesis and biological evaluation of novel thiosemicarbazide analogues as potent anticonvulsant agents Bioorganic Chemistry 54: 68-72
Nicolaou, K.C.; Valiulin, R.A. 2013: Synthesis and biological evaluation of new paclitaxel analogs and discovery of potent antitumor agents Organic and Biomolecular Chemistry 11(25): 4154-4163
Nicolaou, K.C.; Wang, Y.; Lu, M.; Mandal, D.; Pattanayak, M.R.; Yu, R.; Shah, A.A.; Chen, J.S.; Zhang, H.; Crawford, J.J.; Pasunoori, L.; Poudel, Y.B.; Chowdari, N.S.; Pan, C.; Nazeer, A.; Gangwar, S.; Vite, G.; Pitsinos, E.N. 2016: Streamlined Total Synthesis of Uncialamycin and its Application to the Synthesis of Designed Analogues for Biological Investigations Journal of the American Chemical Society 138(26): 8235-8246
Özadalı, K.; Özkanlı, F.üg.; Jain, S.; Rao, P.P.N.; Velázquez-Martínez, C.A. 2012: Synthesis and biological evaluation of isoxazolo[4,5-d]pyridazin-4-(5H)-one analogues as potent anti-inflammatory agents Bioorganic and Medicinal Chemistry 20(9): 2912-2922
Gliszczyńska, A.; Niezgoda, N.; Gładkowski, W.; Czarnecka, M.; Świtalska, M.; Wietrzyk, J. 2016: Synthesis and Biological Evaluation of Novel Phosphatidylcholine Analogues Containing Monoterpene Acids as Potent Antiproliferative Agents Plos one 11(6): E0157278
Xu, H.; Su, X.; Guo, M.-B.; An, R.; Mou, Y.-H.; Hou, Z.; Guo, C. 2020: Design, synthesis, and biological evaluation of novel miconazole analogues containing selenium as potent antifungal agents European Journal of Medicinal Chemistry 198: 112360
Yang, Y.-S.; Lu, X.; Zeng, Q.-X.; Pang, J.; Fan, T.-Y.; You, X.-F.; Tang, S.; Wang, Y.-X.; Song, D.-Q. 2019: Synthesis and biological evaluation of 7-substituted cycloberberine derivatives as potent antibacterial agents against MRSA European Journal of Medicinal Chemistry 168: 283-292
Song, D.; Zhang, N.; Zhang, P.; Zhang, N.; Chen, W.; Zhang, L.; Guo, T.; Gu, X.; Ma, S. 2021: Design, synthesis and evaluation of novel 9-arylalkyl-10-methylacridinium derivatives as highly potent FtsZ-targeting antibacterial agents European Journal of Medicinal Chemistry 221: 113480
Mao, J.; Kuranaga, T.; Hamamoto, H.; Sekimizu, K.; Inoue, M. 2015: Rational design, synthesis, and biological evaluation of lactam-bridged gramicidin A analogues: discovery of a low-hemolytic antibacterial peptide Chemmedchem 10(3): 540-545