Morphinones

Dibenz[h,e]azepine-6,11-diones ent-Morphinan nomenclature, 1, 29 Morphinan, 1,2,3,4-tetrahydro-nomenclature, 1, 29 14-a-Morphinan, N-methyl-synthesis, 1, 480 Morphinans nomenclature, 1, 29 as pharmaceuticals, 1, 148 synthesis, 2, 377 Morphine, 2, 512 as analgesic, 1, 167 as metabolite of normorphine, 1, 235 as pharmaceutical, 1, 146, 147, 148 synthesis, 1, 480 Morphine alkaloids structure, 4, 534 Morphin-7-en nomenclature, 1, 29 Morphinone, dihydro-as pharmaceutical, 1, 147 Morpholine — see also 1,4-Oxazine, tetrahydrocarcinogenicity, 1, 229 corrosion inhibitor, 1, 409 metabolism, 1, 226 nomenclature, 3, 996 structure, 2, 5 synthesis, 2, 89 Morpholine, 4-aciyloyl-polymers, 1, 291 Morpholine, alkenyl-polymers, 1, 291... 

Production of morphinone as a metabolite of morphine and its physiological role 99YZ249. 

Morphinone can be reduced by Pseudomonas putida MIO to hydromorphone using an enzyme of which one of the subunits contains FMN (French and Bruce 1994). 

Basran J, RJ Harris, MJ Sutcliffe, NS Scrutton (2003) H-tuneling in the multiple H-transfers of the catalytic cycle of morphinone reductase and in the reductive half-reaction of the homologous pentaerythritol tetranitrate reductase. J Biol Chem 278 43973-43982. 

French CE, NC Bruce (1994) Purification and characterization of morphinone reductase from Pseudomonas putida MIO. Biochem J 301 97-103. 

The report of Basran et al. (entry 5 of Table 2) contains two studies involving hydride transfer with nicotinamide cofactors. In morphinone-reductase catalyzed reduction by NADH of the flavin cofactor FMN (schematic mechanism in Fig. 5), the primary isotope effects are modest (around 4 for H/D), but exhibit a small value of Ajj/Aq (0.13) and an exalted isotopic difference in energies of activation (8.2kJ/mol) that alone would have generated an isotope effect around 30. The enthalpies of activation are in the range of 35-45 kJ/mol. This is behavior typical of Bell tunneling as discussed above. It can also be reproduced by more complex models, as will be discussed in later parts of this review. 

The alcoholic hydroxyl at C-6 can be modified (as in heroin) or even omitted. For instance, heterocodeine (5.87, morphine-6-methylether) is about five times more active than morphine. The 6-keto derivative (5.88, morphinone) and the 6-methylene analog are both active analgesics. 

Reduction of the amide (123 R1 = R2 = OMe) with sodium aluminium hydride gave a mixture of the bases (125 R1 = R2 = OMe), (127), and (130),165 and the last of these lost carbon monoxide when heated with tris(tri-phenylphosphine)rhodium chloride in benzene to give the dimethyl ketal of 14/3-methylcodeinone, which could be hydrolysed to 14j8-methylcodeinone, the 7,8-dihydro-derivative of which proved to be identical with material previously prepared by a different route (see Volume 9, p. 116). The corresponding morphinone and dihydromorphinone have been prepared.164... 

Nelson and Elliott (1967) compared the effects of morphine, morphinone and thebaine on respiration and... 

HYDRIDE-TRANSFER REACTIONS INVOLVING OTHER COFACTORS Morphinone reductase... 

The other factor that may determine the type of cell death is the chemical structure of inducing agents [14]. We have recently found that u,(>-unsaluraled ketones such as 4,4-dimethyl-2-cyclopenten-l-one, a-methy-lene-y-butyrolactone, 5,6-dihydro-2H-pyran-2-one [15], codeinone [16], and morphinone [17] and a-hydroxylketones such as 3,3,3-trifluoro-2-hydroxy-1-phenyl-1-propanone induced caspase-independent cell death [18], induced vacuolization or autophagosome formation engulfing organelles, but without induction of apoptosis markers. 

---