From isoquinoline derivatives

Substituted 4-aryl-1 -oxo-1,2-dihydropyrazino[l, 2-i]isoquinolinium salts 402 were obtained when 3-substituted isoquinolines 401 were cleaved from a polymer by treatment 25% TFA (00MIP5). c/i-3,lla-H-3-Phenyl-1,2,3,4,11,11 fl-hexahydropyrazino[l, 2-i]isoquinoline-1,4-dione (404) formed when isoquinoline derivative 403 was cleaved from a resin with 25% TFA during an automated solid-phase synthesis (98BMCL2369). 

Hasrat JA, De Bruyne T, De Backer JP, Vauquelin G, Vlietinck AJ. Isoquinoline derivatives isolated from the fruit of Annona muricata as 5-HTergic 5-HT1A receptor agonists in rats unexploited antidepressive (lead) products. J Pharm Pharmacol 1997 49 1145-1149. 

Cyano-4-hydroxypyridazino[l,6- ]quinolinium betaine 67 could be isolated from the reaction mixture of 1-amino-2-ethoxycarbonylquinolinium mesitylensulfonate and acrylonitrile in a few percent. Reaction of the 2-amino-1-ethoxycarbonylisoquinolinium salt with acrylonitrile afforded only a pyrazolo[5,l- ]isoquinoline derivative. 

The Delft synthesis makes use of an acid-catalyzed ring closure - in fact an intramolecular aromatic alkylation - of a l-(3,5-dihydroxy-4-methoxybenzyl) isoquinoline derivative that is prepared starting from (natural) gallic acid. One of the hydroxyl groups is removed via a Pd/ C hydrogenation of the benzyl ether. Other catalytic steps play an important role some steps were improved recently [27]. The crucial step in the Rice synthesis makes use of a l-(2-bromo-5-hydroxy-4-methoxybenzyl)isoquinoline derivative that is also cyclized in an acid-catalyzed ring closure to the morphinan skeleton, followed by catalytic removal of the bromo substituent (Scheme 5.8). 

Dihydropyridines have also been starting points for stereospecific syntheses of hydro-phenanthridines and isoquinolines. Interest exists in these compounds because of the occurrence of this structural feature in alkaloids. For example, isoquinuclidine (263), derived from JV-alkoxycarbonyl-l,2-dihydropyridine, undergoes a Cope rearrangement to give the isoquinoline derivative (264) (80JA6157). Further chemical transformations of (264) provided a formal total synthesis of reserpine (Scheme 50). 

If quinoline derivatives are expected to be synthesized by this procedure, the starting cycloalkene should contain a cyclobutene ring. When cyclobutene derivative 65c is reacted with Ig under ethylene gas, isoquinoline derivative 66c is obtained in 60% yield. Furthermore, cyclic amino acid ester 66d is obtained from glycine derivative 65d in 75% yield by a one-step reaction. Various isoquinolone derivatives 66e-66i are also synthesized from cyclobutenyl amides... 

The opium is obtained from the opium poppy Papaver somniferum. It contains two type of alkaloids e.g. phenanthrene derivatives (morphine, codeine thebaine) and benzyl isoquinoline derivatives (papaverine and noscapine). 

Iodophenethylamine derivatives were found to undergo palladium catalysed cyclization to indolines.45 Starting from the appropriate tetrahydro-isoquinoline derivative the reaction was extended by Buchwald to the preparation of tricyclic natural products (3.37.),46... 

Most annulation procedures, which produce nitrogen heterocycles start from a tert-butvlimine, where the sacrificial organic moiety is released in the course of the process as isobutene. Ring closure of the 2-iodoveratraldehyde derivative shown in 4.34. and ethyl phenylpropiolate, for example, led to the formation of the appropriate isoquinoline derivative in excellent yield. Formation of the isomeric 4-phenylisoquinoline compound was also observed (5%).42... 

The opium alkaloids, which are obtained from Papaver somniferum, contain two groups of compounds compounds with phenanthrene derivatives, consisting of morphine, codeine, and thebaine and compounds with isoquinoline derivatives, consisting of papaverine and noscapine. 

Nickel(O) complexes catalyse [2+2+2] cycloaddition. Catalytic asymmetric synthesis of isoquinoline derivative 134 is possible based on enantiotopic group-selective formation of the nickelacyclopentadiene 133 from 132 using the Ni(0) complex coordinated by a chiral ligand under acetylene atmosphere [56]. 

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