Tetrahydro isoquinoline alkaloids

AT-methyl protons in the seven-membered ring absorb (5 2-16) at abnormally low frequency compared with those in normal tetrahydro-isoquinoline alkaloids. (56)... 

Benzyl(tetrahydro)isoquinoline alkaloids. B. a. occur especially in various Annonaceae, Lauraceae, Rhamnaceae, Ranunculaceae, Papaveraceae, and Fa-baceae. They are soluble in ethanol, chloroform, ether and poorly soluble in water. Laudanidine is toxic, it acts as a convulsive and respiratory stimulant, laudan-osine is a tetanic toxin, orientaline is the biosynthetic precursor of isothebaine. Pwtosinomenine occurs especially in Erythrina lithosperma (Fabaceae). Papaverine [ 1 -(3,4-dimethoxybenzyl)-6,7-dimethoxyiso-quinoline] acts as a parasympathicolyticum relaxing smooth musculature, it promotes cerebral perfusion (vasodilatation). It is an antiasthmatic and oral anti-spasmodic agent used in the treatment of gastrointestinal spasms LD50 (mouse i. v.) 25 mg/kg. Reticuline is an important precursor of protoberberines, morphi-nans, aporphines, spirobenzylisoquinolines, and rhoeadine alkaloids. 

Table Data of Benzyl(tetrahydro)isoquinoline alkaloids.

DioncophyNiiie C, DioncopeHatine A see naph-thyl(tetrahydro)isoquinoline alkaloids. 

MkheNamines. Atropisomeric dimeric naphthyl-(tetrahydro)isoquinoline alkaloids from the tropical lianas Ancistrocladus korupensis and A. abbreviatus. C46H48N2O8, Mr 756.89. 

Table Data of Naphthyl(tetrahydro)isoquinoline alkaloids.

Pavine and iso >avine aHtaMds. The P. a. are derivatives of benzyl(tetrahydro)isoquinoline alkaloids that occur in various species of, in particular, the Pa-paveraceae, Berberidaceae, Ranunculaceae, Lauraceae, and Menispermaceae (see table). Argemonine exhibits curare-like properties. 

PheneUiyHetrahydroisoquinoliiie alkaloids. While the benzy l(tetrahydro)isoquinoline alkaloids are built up form a Cj-C2 unit and dopamine, the phenethyl-tetrahydroisoquinolines are formed from dopamine and a (- 3 unit. Similar to the benzylisoquinolines, the compounds can undergo a series of secondary reactions to furnish the corresponding homo compounds. They can be classified into 7 different groups ... 

Reticulina see benzyl(tetrahydro)isoquinoline alkaloids and streptomycin. 

Bruhn JG, Lundstrom J (1976) Alkaloids of Carnegia gigantea. Arizonine, a new tetrahydro-isoquinoline alkaloid. Lloydia 39 197- 203... 

The introduction of methoxyl groups at C-6 and C-l into the tetrahydro-isoquinoline system, a common substitution pattern in the alkaloids, as in... 

Since many isoquinoline alkaloids incorporate a guiacol moiety, we first tried to oxidize the most accessible 6-methoxy- and 7-methoxy-l,2,3,4-tetrahydroisoquinolinols (types A and B) with LTA. Later, tetrahydro-isoquinolinols of type C were also used. In spite of Wessely s statement (16) that LTA oxidation of both vanillin and isovanillin affords the corresponding o-quinol acetates, for a while we were able to obtain not the o-quinol acetate 2 from corypalline (1) but the p-quinol acetate 3 (17). At the outset of our study (IS), LTA oxidation of isocorypalline (4) gave no isolable o-quinol acetate 5, 4-acetoxyisocorypalline (6) being isolated instead. 

The absolute configurations of (If , 4R)-l,2,3,4-tetrahydro-4-hydroxy-6-methoxy-2-methyl-l-phenylisoquinoline (31) and its epimer (IS, 4R), synthesised fromD-(+)-2-amino-l-(3-hydroxyphenyl)ethanol, have been determined with the aid of n.m.r. spectral and o.r.d. and c.d. measurements.42 These results may prove to be useful in the determination of the absolute configuration of 1-phenyl-isoquinoline alkaloids. In this regard, another report on the conformation and configuration of differently substituted tetrahydroisoquinolines may be consulted.43... 

Fractions from the condensate of Burley tobacco afforded two terpenoid alkaloids, l,3,6,6-tetramethyl-5,6,7,8-tetrahydro-isoquinolin-8-one (116)... 

The IR spectra of oxyrhoeagenine (VIII) showed that the compound contains a six-membered lactone ring in contrast to phthalideisoquinoline alkaloids. A substantial difference in pA values for these two lactone types was also noticed (430). It followed that the suggested tetrahydro-isoquinoline constitution of the rhoeadine alkaloids had to be revised (430). 

The large group of alkaloids of the isoquinoline type ranges in complexity from the simple isoquinolines, more exactly defined as simple tetrahydro-isoquinolines, with only one aromatic nucleus, to the complicated structures of the bisbenzylisoquinolines. 

Outside these two families, however, no other plants have been found to produce real tetrahydro-, dihydro-, and fully aromatic isoquinoline alkaloids in a polyacetate way. Closely related, but chemically a lactam, is siamine (40) from Cassia siamea Lam. (Leguminosae) (42). The structure suggests a biogenesis from a pentaketide precursor 41 (Fig. 2), thus requiring one acetate unit less than each of the naphthyl isoquinoline alkaloid moieties. 

This unusual biosynthetic pathway—the synthesis and regio-controlled cyclization of p-polyketones, optionally leading to tetrahydro-, dihydro-, or fully conjugated isoquinolines, or to naphthalenes and respective naphthoquinones— could be imitated effieiently in vitro. The smooth course of these chemical model reaetions underlines the chemieal plausibility of the proposed biogenetie scheme and simultaneously provides the basis for a first and variable total synthesis of naphthyl isoquinoline alkaloids. 

The alkaloid anhalonine was generated by methylation of the corresponding l,2,3,4-tetrahydro-6,7-dimetoxy-8-hydroxy-l-methylisoquinoline (anhaloni-dine) Kreysigine, a benzocyclohepta-isoquinoline alkaloid, was obtained by the methylation of l,10-dihydroxy-2,l l,12-trimethoxy-4,5,6,6a,7,8-hexahydrobenzo[6,7] cyclohepta [l,2,3-(/]isoquinoline (floramultine alkaloid) (Figure 1.5d). 

The dehydroderivatives of the main phenolic alkaloids and the glyoxylic and pyruvic acid condensation products, peyoruvic acid and peyoxyhc acid, are interesting in the light of biosynthetic considerations, as these compounds may be intermediates in the biogenetic transformation of phenethylamines into tetrahydro-isoquinolines (cf. Lundstrom 1983). 

Baser KH (1982) Isolation and identification of anisaldehyde and three alkaloids from leaves of Thalictrum minus var. microphyllum. J Nat Prod 45 704-706 Bell EA, Nulu JR, Cone C (1971) L-Dopa and L-3-carboxy-6,7-dihydroxy-1,2,3,4-tetrahydro-isoquinoline, a new amino acid from seeds of Mucuna mutisiana. Phytochemistry 10 2191-2194... 

Brochmann-Hanssen E, Cheng CY (1984) Biosynthesis of a narcotic antagonist. Conversion of N-allylnorreticuline to N-allylnormorphine in Papaver somniferum. J Nat Prod 47 175-176 Brochmann-Hanssen E, Furuya T (1964) A new opium alkaloid. Isolation and characterization of ( )-l-(3 -hydroxy-4 -methoxybenzyl)-2-methyl-6-methoxy-7-hydroxy-l,2,3,4-tetrahydro-isoquinoline [( )-reticuline]. Planta Med 12 328-333 Brochmann-Hanssen E, Nielsen B (1965) (+)-Reticuhne - a new opium alkaloid. Tetrahedron Lett 1271-1274... 

Coutts IGC, Hamblin MR, Tinley EJ (1979) The enzymatic oxidation of phenolic tetrahydroiso-quinoline-1-carboxylic acids. J Chem Soc Perkin Trans 1 2744-2750 Davis VE, Cashaw JL, McMurtrey KD, Ruchirawat S, Nimit Y (1982) Metabolism of tetrahydro-isoquinolines and related alkaloids. In Bloom F, Barchas J, Sandler M, Usdin E (eds) Beta-carbolines and tetrahydroisoquinolines. Liss, New York, p 99 Furuya T, Nakano M, Yoshikawa T (1978) Biotransformation of (RS)-reticuline and morphinan alkaloids by cell cultures of Papaver somniferum. Phytochemistry 17 891-893 Gates M (1953) Conversion of codeinone to codeine. J Am Chem Soc 75 4340-4341 Graves JMH, Smith WK (1967) Transformation of pregnenolone and progesterone by cultured plant cells. Nature (London) 214 124 8-1249... 

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