Molecular Morphinans

Methyl 2,3,5-tri-Q-acetyl a and p-D-ribofuranoside, 86 Michael reaction, 221-242 Mixed anhydride, 353 Molecular graphic techniques, 353 Molecular rearrangements, 183-190 ( )-Monomorine, 213 Monothioacetal, 21 Morphinans, 356-357... 

Work on the relationship between chemical structure and pharmacological activity of morphinans to 1966 has been reviewed by Hellerbach et al. s) and morphinans with antagonist properties were reviewed in 1973.(158) As is the case for 4,5-epoxymorphinans (Chapter 2) and benzomorphans (Chapter 4), molecular geometry is the major structure-biological activity influence, although the nature of the N-substituent imparts significant qualitative and quantitative variations in morphinan pharmacology. 

The model adequately accommodates most structural variants of morphine and the morphinan and benzomorphan groups of analgesic. All such ligands are closely related in the molecular shape and absolute configurational relationships of the more active antipodal forms. Additional receptor sites are required to interact with ... 

Morishige T, Dubouzet E, Choi K-B, Yazaki K, Sato F. Molecular cloning of columbamine O- methyltransferase from cultured Coptis japonica cells. Eur. J. Biochem. 2002 269 5659-5667. Hirata K, Poeaknapo C, Schmidt J, Zenk MH. 1,2-Dehydroreti-culine synthase, the branch point enzyme opening the morphinan biosynthetic pathway. Phytochemistry 2004 65 1039-1046. De-Eknamktil W, Zenk MH. Purification and properties of 1,2-dehydroreticuUne reductase from Papaver somniferum seedlings. Phytochemistry 1992 31 813-821. 

Fig. 15 K-Agonists in training set and their property spheres. Training set comprising four morphinans (TRK-820, KNT-63, KNT-62, and NS-22), two arylacetamides (U-69593 and U-50488H), and one neoclerodane diterpene (salvinorin A). The spheres on each molecule are property spheres for molecular superposition. The colors of the spheres indicate the following properties hydrophobic (HP, black)-, aromatic (AR, green)-, hydrogen-bond donors (HD, blue)-, hydrogen-bond acceptors (HA, red)-, and hydrogen-bond donors/acceptor (DA, violet). Large and small spheres indicate radii of 1 and 0.5 A, respectively. p/K = S, (p)/S i(K)...

Molecular dynamics, 173 Molecular modeling, 135 Molecular modelling, 115 Morphinans, 337... 

Recently, opium poppy (P. somniferum) has emerged as a model system to investigate alkaloid metabolism. Great progress towards the elucidation of BIA metabolism including the well-known morphinan alkaloids has been made at the biochemical and molecular levels and a restricted number of enzyme families have been implicated. 

Kinetic inhibition experiments revealed that the molecular action of the base on the lipase is a noncompetitive inhibititm — i.e., the base attaches itself to the lipase at a site other than the active site - which inhibits the transformation of one enantiomer but not that of its mirror image. Moreover, the chirality of the base has only a marginal impact on the selectivity enhancement effect. The general applicability of this method - impeded by the high cost of morphinan alkaloids and their questionable use for large-scale synthesis — has been extended by the use of more simple amines such as N, A -dimethyl-4-methoxyphenethylamine (DMPA) [235]. 

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