reticuline and coclaurine

A general procedure for the synthesis of 1-benzyl-1,2,3,4-tetrahydroisoquinolines was developed, based on organocatalytic, regio- and enantioselective Pictet-Spengler reactions (86-92% ee) of N-(o-nitrophenylsulfenyl)-2-arylethylamines with arylacetaldehydes. The presence of the o-nitrophenylsulfenyl group, together with the MOM-protection in the catechol part of the tetrahydroisoquinoline ring system, appeared to be a productive combination. To demonstrate the versatility of this approach, 10 biologically and pharmaceutically relevant alkaloids were prepared using (R)-TRIP as the chiral catalyst: (R)-norcoclaurine, (R)-coclaurine, (R)-norreticuline, (R)-reticuline, (R)-trimemetoquinol, (R)-armepavine, (R)-norprotosinomenine, (R)-protosinomenine, (R)-laudanosine, and (R)-5-methoxylaudanosine.

Topics: Alkaloids; Benzylisoquinolines; Biological Products; Catalysis; Cyclization; Ethylamines; Isoquinolines; Molecular Structure; Organic Chemistry Phenomena; Stereoisomerism; Tetrahydroisoquinolines

(+/-)-Higenamine (Hig. demethylcoclaurine) is a cardiotonic principle from aconite root. (+)-R-Coclaurine (Coc) and (+)-S-reticuline (Ret) are compounds contained in the dried buds of Magnolia salicifolia MAXIM. All of these alkaloids possess a common chemical structure: tetrahydroisoquinoline. Coc and Ret showed negative inotropic effects in contrast to the positive inotropic effects of Hig in papillary muscles of guinea pigs. Coc and Ret shifted to the right the concentration-contraction curves of Hig. Hig shifted in parallel to the left the Ca2+ curve, and it tended to shift to the left the isoproterenol (Isp)-induced response curve. In contrast, Coc and Ret inhibited the Ca2+ curve and the low concentration range of the Isp-induced curve, and it potentiated the high concentration ranges of Ca2+ and Isp. Coc and Ret showed actions that were reversed in direction to those of Hig, as clearly demonstrated in the Ca2+ curve.

Topics: Alkaloids; Animals; Benzylisoquinolines; Cardiotonic Agents; Guinea Pigs; In Vitro Techniques; Isoquinolines; Male; Medicine, East Asian Traditional; Myocardial Contraction; Papillary Muscles; Plant Extracts; Stereoisomerism; Tetrahydroisoquinolines

An intracerebroventricular injection of d-coclaurine (50 micrograms), a benzyltetrahydroisoquinoline alkaloid extracted from Magnolia salicifolia, produced a slight increase in 3,4-dihydroxyphenylacetic acid level and a significant increase in homovanillic acid level in the mouse striatum. Another alkaloid d-reticuline (200 micrograms) increased only homovanillic acid level. An intracerebroventricular pretreatment with d-coclaurine (50 micrograms) did not antagonize suppressive effect of apomorphine on l-dopa formation produced by gamma-butyrolactone (750 mg/kg i.p.) plus aromatic amino acid decarboxylase inhibitor, NSD-1015 (100 mg/kg i.p.). These results suggest that d-coclaurine blocks postsynaptic but not presynaptic dopamine receptors in the mouse striatum.

Topics: 3,4-Dihydroxyphenylacetic Acid; 4-Butyrolactone; Alkaloids; Animals; Antipsychotic Agents; Benzylisoquinolines; Corpus Striatum; Homovanillic Acid; Injections, Intraventricular; Isoquinolines; Levodopa; Male; Mice; Phenylacetates

Topics: Alkaloids; Animals; Behavior, Animal; Benzylisoquinolines; Dopamine; Isoquinolines; Male; Mice; Plant Extracts