539-90-2Relevant articles and documents
Total Synthesis and Functional Evaluation of Fourteen Derivatives of Lysocin E: Importance of Cationic, Hydrophobic, and Aromatic Moieties for Antibacterial Activity
Kaji, Takuya,Murai, Motoki,Itoh, Hiroaki,Yasukawa, Jyunichiro,Hamamoto, Hiroshi,Sekimizu, Kazuhisa,Inoue, Masayuki
supporting information, p. 16912 - 16919 (2016/11/16)
Lysocin E (1) is a structurally complex 37-membered depsipeptide comprising 12 amino-acid residues with an N-methylated amide and an ester linkage. Compound 1 binds to menaquinone (MK) in the bacterial membrane to exert its potent bactericidal activity. To decipher the biologically important functionalities within this unique antibiotic, we performed a comprehensive structure-activity relationship (SAR) study by systematically changing the side-chain structures of l-Thr-1, d-Arg-2, N-Me-d-Phe-5, d-Arg-7, l-Glu-8, and d-Trp-10. First, we achieved total synthesis of the 14 new side-chain analogues of 1 by employing a solid-phase strategy. We then evaluated the MK-dependent liposomal disruption and antimicrobial activity against Staphylococcus aureus by 1 and its analogues. Correlating data between the liposome and bacteria experiments revealed that membrane lysis was mainly responsible for the antibacterial functions. Altering the cationic guanidine moiety of d-Arg-2/7 to a neutral amide, and the C7-acyl group of l-Thr-1 to the C2 or C11 counterpart decreased the antimicrobial activities four- or eight-fold. More drastically, chemical mutation of d-Trp-10 to d-Ala-10 totally abolished the bioactivities. These important findings led us to propose the biological roles of the side-chain functionalities.
The Mechanism of the β-Acyloxyalkyl Radical Rearrangement: Kinetic and 18O-Labelling Studies
Beckwith, Athelstan L. J.,Duggan, Peter J.
, p. 1777 - 1783 (2007/10/02)
Experiments with 18O-enriched substrates indicate that the rearrangement of 2-butanoyloxy-2,2-dimethyl radical 1 (R=Pr) by migration of the acyloxy group involves complete transposition of the ether and carbonyl oxygen atoms, whereas the similar but much faster rearrangement of the substituted cholestanyl radical 11 proceeds with only 24percent transposition.The rearrangement of 1 is considered to involve a five-membered cyclic transition state 2, while that of 11 probably proceeds via a tight anion-radical-cation pair 21.
CATALYSED LIQUID PHASE OXIDATION OF ACETALS BY MOLECULAR OXYGEN
Vcelak, Jaroslav,Klimova, Miroslava,Chvalovsky, Vaclav
, p. 847 - 866 (2007/10/02)
Nine different acetals have been oxidized in the presence of Co(OOCCH3)2*4H2O under isobaric conditions (0.1 - 0.2 MPa O2) while following the uptake of molecular oxygen.The reactivity of acetals was expressed by the rate constants of the autocatalytic model of oxidation.The main product of the oxidation are alcohols, esters and acids.The distribution of products and the total reactivity of acetals are controlled by the structure of both parts of acetal molecule.The dominant effects of the course of the reaction exerts the type of carbon atoms on which radicals are formed.The oxidation is accompanied by consecutive and co-oxidation reactions, by deactivation of the catalysts and by decarbonylation of intermediate products.The effect of oxygen pressure is reported and the more detailed radical mechanism of the oxidation is proposed.