53153-46-1Relevant articles and documents
Spectroscopic and Kinetic Evidence for the Tautomer of 7-deoxyalklavinone as an Intermediate in the Reductive Coupling of Aclacinomycin A
Kleyer, Don L.,Gaudiano, Giorgio,Koch, Tad H.
, p. 1105 - 1109 (2007/10/02)
Reduction of aclacinomycin A (7) with an excess of dl-bi(3,5,5-trimethyl-2-oxomorpholin-3-yl) (11) in Trizma-buffered methanol solvent in the absence of oxygen gave 7-deoxyalkavinone (8), bi(7-deoxyalkavinon-7-yl) (9), 5,6-dihydro-3,5,5-trimethyl-1,4-oxazin-2-one (12), and 3,5,5-trimethyl-2-oxomorpholine (13).The reducing agent was 3,5,5-trimethyl-2-oxomorpholin-3-yl (5) resulting from bond homolysis of 11.The relative yields of 8 and 9 were a function of the initial concentrations of 7 and 11 and the reaction time.The semiquinone 15 of 7 was observed as anintermediate by EPR spectroscopy.Uv-visible spectroscopic monitoring revealed the formation of the tautomer 14 of 7-deoxyalklavinone as a second intermediate in the formation of both 8 and 9.The tautomer showed absorption at 350 and 548 nm.Reaction of 9 with 11 resulted in reductive cleavage of 9 to 8 and disproportionation of 11 to 12 and 13.The mechanism proposed for the reduction of 7 is shown in Scheme III and includes protonation of 14 to give 8 and coupling of 14 followed by oxidation with 12 to give 9.The decay of the tautomer absorption followed mixed kinetics, first and second order in 14.Nonlinear least-squares analysis of the decay gave a pseudo-first-order rate constant for protonation equal to 3.36x10-3s-1 and a second-order rate constant for coupling equal to approximately 180 M-1s-1.The tautomer 14 of 7-deoxyalklavinone is protonated in buffered methanol 15 times slower than the tautomer 6 of 7-deoxydaunomycinone, thus allowing the coupling reaction to take place.The difference in reactivity of the tautomers may be relevant to the tumorresponse and toxicity of the two anthracyclines.
Electron-Transfer Chemistry of the Merostabilized 3,5,5-Trimethyl-2-morpholinon-3-yl Radical
Burns, John M.,Wharry, Donald L.,Koch, Tad H.
, p. 849 - 856 (2007/10/02)
Reductions of 5,6-dihydro-5,5-dimethyl-3-phenyl-1,4-oxazin-2-one (6) to 5,5-dimethyl-3-phenyl-2-morpholinone (8), 2-benzoyl-4,4-dimethyl-2-oxazoline (9) to 2-(hydroxyphenylmethyl)-4,4-dimethyl-2-oxazoline (10), 4-(diphenylmethylene)-2,5-cyclohexadienone (12a) to diphenyl(p-hydroxyphenyl)methane (14a), 4--2,5-cyclohexadienone (12b) to tris(p-hydroxyphenyl)methane (14b), benzil (17) to benzoin, and substituted benzils (17a-c) to substituted benzoins by 3,5,5-trimethyl-2-morpholinon-3-yl radical are described.Intermediate radicals 5,5-dimethyl-3-phenyl-2-morpholinon-3-yl (7), diphenyl(p-hydroxyphenyl)methyl (13a), and tris(p-hydroxyphenyl)methyl (13b) are characterized by EPR spectroscopy.Kinetic analyses of the reductions of 6, 9, 17, and 17a-c are described, and mechanisms and rate laws are shown in Schemes II, III, and VII.Reduction reactions most likely occur by electron transfer.Evidence for electron transfer includes an isotope effect for disproportionation of 1 equal to 1.10 +/- 0.09, correlation of the logarithm of the relative rates of reduction of benzils with ?+ with a ρ of 1.7 +/- 0.1, and observation of electron transfer from 1 to tetracyanoethylene, dianisyloxoammonium perchlorate (21), and paraquat (20).
