919286-02-5Relevant academic research and scientific papers
Discovery of novel FabF ligands inspired by platensimycin by integrating structure-based design with diversity-oriented synthetic accessibility
Fisher, Martin,Basak, Ramkrishna,Kalverda, Arnout P.,Fishwick, Colin W. G.,Bruce Turnbull,Nelson, Adam
supporting information, p. 486 - 494 (2014/01/06)
An approach for designing bioactive small molecules has been developed in which de novo structure-based ligand design (SBLD) was focused on regions of chemical space accessible using a diversity-oriented synthetic approach. The approach was exploited in the design and synthesis of a focused library of platensimycin analogues in which the complex bridged ring system was replaced with a series of alternative ring systems. The affinity of the resulting compounds for the C163Q mutant of FabF was determined using a WaterLOGSY competition binding assay. Several compounds had significantly improved affinity for the protein relative to a reference ligand. The integration of synthetic accessibility with ligand design enabled focus to be placed on synthetically-accessible regions of chemical space that were relevant to the target protein under investigation.
Efforts towards the identification of simpler platensimycin analogues-the total synthesis of oxazinidinyl platensimycin
Wang, Jingxin,Lee, Vincent,Sintim, Herman O.
supporting information; experimental part, p. 2747 - 2750 (2009/12/06)
The total synthesis and biological testing of oxazinidinyl platensimycin, the methyl ester analogues, and the simplified oxazinidinyl analogue were investigated to identify simpler platensimycin analogues. The study also investigated the possibilities of replacing enone moiety of platensimycin with the oxazinidinyl ring to create a potential bioisostere compound. The study examined the possibilities to replace the tetracyclic core structure of platensimycin with other motifs that are synthetically easier to access. Proposed methods can applied to the construction of other polycyclic motifs found in the other natural or non-natural molecules. The results show that the enone moiety of platensimycin's core structure is sensitive to modifications.
Total synthesis of platensimycin and related natural products
Nicolaou,Li, Ang,Edmonds, David J.,Tria, G. Scott,Ellery, Shelby P.
supporting information; experimental part, p. 16905 - 16918 (2010/04/04)
Platensimycin is the flagship member of a new and growing class of antibiotics with promising antibacterial properties against drug-resistant bacteria. The total syntheses of platensimycin and its congeners, platensimycins B1 and B3, platensic acid, methyl platensinoate, platensimide A, homoplatensimide A, and homoplatensimide A methyl ester, are described. The convergent strategy developed toward these target molecules involved construction of their cage-like core followed by attachment of the various side chains through amide bond formation. In addition to a racemic synthesis, two asymmetric routes to the core structure are described: one exploiting a rhodium-catalyzed asymmetric cycloisomerization, and another employing a hypervalent iodine-mediated de-aromatizing cyclization of an enantiopure substrate. The final two bonds of the core structure were forged through a samarium diiodide-mediated ketyl radical cyclization and an acid-catalyzed etherification. The rhodium-catalyzed asymmetric reaction involving a terminal acetylene was developed as a general method for the asymmetric cycloisomerization of terminal enynes.
An efficient entry to amino-substituted resorcylic acid derivatives for the synthesis of platensimycin and analogues
Heretsch, Philipp,Giannis, Athanassios
, p. 2614 - 2616 (2008/02/13)
An efficient entry to protected amino-substituted resorcylic acid derivatives, methyl 3- or 5-amino-2,4-bis(methoxymethoxy)benzoate, is reported. Both derivatives can be used for the synthesis of platensimycin and its analogues. Georg Thieme Verlag Stuttg
Total synthesis of platensimycin
Nicolaou,Li, Ang,Edmonds, David J.
, p. 7086 - 7090 (2007/10/03)
(Chemical Equation Presented) Beat the superbugs: The newly discovered antibiotic platensimycin (1) promises to combat current drug-resistant infections. The natural product shows potent activity against Gram-positive bacteria and contains a novel molecul
