82267-36-5Relevant articles and documents
SUSTAINED RELEASE DELIVERY SYSTEMS COMPRISING TRACELESS LINKERS
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Page/Page column 152, (2018/11/22)
Described herein are drug delivery systems for delivering biologically active agents comprising primary or secondary amines, or a ring nitrogen atom of an azaheteroaryl ring, pharmaceutically acceptable salts thereof, drug delivery reagents related theret
β-Secondary Kinetic Isotope Effects in the Clavaminate Synthase-Catalyzed Oxidative Cyclization of Proclavaminic Acid and in Related Azetidinone Model Reactions
Iwata-Reuyl, Dirk,Basak, Amit,Townsend, Craig A.
, p. 11356 - 11368 (2007/10/03)
Clavaminate synthase is an Fe(II)/α-ketoglutarate-dependent oxygenase that catalyzes three mechanistically distinct reactions in the course of clavulanic acid biosynthesis. Clavulanic acid is of significant chemical importance as a potent inhibitor/inactivator of β-lactamase enzymes, a prominent means of bacterial resistance to, for example, penicillin. Primary and α-secondary T(V/K) kinetic isotope effects have been determined in earlier work for the clavaminate synthase-catalyzed oxidative cyclization of proclavaminic acid, one of the three reactions mediated by this enzyme. In this paper the β-secondary deuterium kinetic isotope effect for this reaction has been determined using remote 3H and 14C labels in an attempt to distinguish between radical or cationic intermediates in the reaction as suggested by the magnitudes of the primary and secondary α-effects. The presence of the adjacent azetidinone nitrogen and the intervention of an azetinone intermediate, formally antiaromatic in the resonance form of the amide, make interpretation of the low β-secondary effect (1.056 ± 0.002 for dideuteriation at C-3′) problematic. To assist interpretation of this result, a 4-chloroazetidinone model system has been constructed dideuteriated at C-3 identically to proclavaminic acid and bearing remote radiolabels. Reaction of this substrate at 25°C under both radical and solvolysis conditions afforded β-secondary kinetic isotope effect data for direct comparison to the enzymic reaction. The measured effects are similarly small but strongly dependent on the polarity/acidity of the reaction medium. These results are discussed in terms of the commitment to catalysis and the extent to which amide resonance may be favored in the transition state of the oxidative cyclization.
Synthesis and Stereochemistry of Hypusine, a New Amino Acid in Bovine Brain
Shiba, Tetsuo,Akiyama, Hitoshi,Umeda, Isao,Okada, Satoshi
, p. 899 - 903 (2007/10/02)
Hypusine, a new basic amino acid occurring in the homogenate of bovine brain tissue, was synthesized to determine the absolute structure.Nα-Benzyloxycarbonyl-L-lysine benzyl ester was coupled with (S)- or (R)-4-benzyloxycarbonylamino-1-bromo-2-butanol derived from L- or D-malic acid, respectively.The products were deprotected by catalytic dehydrogenation.One of the synthetic compounds, i.e., (2S,9R)-2,11-diamino-9-hydroxy-7-azaundecanoic acid, was completely identical with natural hypusine in all respects.
