Isoquinoline nucleus

Alkyl Isoquinolines. Coal tar contains small amounts of l-methylisoquinoline [1721-93-3] 3-methylisoquinoline [1125-80-0] and 1,3-dimetliylisoquinoline [1721-94-4J. The 1- and 3-methyl groups are more reactive than others in the isoquinoline nucleus and readily oxidize with selenium dioxide to form the corresponding isoquinoline aldehydes (174). These compounds can also be obtained by the hydrolysis of the dihalomethyl group. The 1- and 3-methyhsoquinolines condense with benzaldehyde in the presence of zinc chloride or acetic anhydride to produce 1- and 3-styryhsoquinolines. Radicals formed by decarboxylation of carboxyUc acids react to produce 1-aIkyhsoquinolines. 

It is considered that in these new forms racemisation or reversible inversion has occurred at the centre of asymmetry in the phthalide group, and that the centre of asymmetry in the isoquinoline nucleus is unaffected. The melting-point, 176°, of each new isomeride is depressed by addition of the corresponding a-narcotine and the specific rotation of l-j3-narcotine, W548 is 101° (CHCI3) or — 59-2° (N. HCl), that of i-a-narcotine, under the same conditions being — 246° and -f 50-4° respectively. 

Aromatic donble bonds may also be nsed effectively to trap the electrophilic intermediate (electrophilic aromatic snbstitntion). The Beckmann rearrangement-cyclization seqnence has fonnd ntihty in the synthesis of the isoquinoline nucleus . ... 

Alkaloids containing the isoquinoline nucleus may be divided into two groups (1) papaverine, narcotine, cotarnine, narcine, and certain others of the opium group, and (2) the hydrastis group including hydrastine, berberine, and canadine (Figure 11.9). 

Hanna and Shutt (146) studied the relationship between the chemical structure and the coronary dilator action of papaverine analogs on anesthetized dogs. The 6-alkoxy-, 5,6-dialkoxy-, and 6,7-dialkoxy-isoquinoline derivatives acted as dilators. The 6,7-dialkoxyisoquinoline derivatives were most effective. Optimum results were obtained when the isoquinoline nucleus was aromatic, but the 3,4-dihydro- and 1,2,3,4-... 

The very fast metal-halogen exchange allows intramolecular cyclization reactions, which are known as Parham cyclizations171. The potential of Parham cyclizations as a useful stereoselective cyclization procedure has proven to be extremely interesting172. Thus, it has been recently demonstrated that iodinated IV-phenethylimides tolerate iodine-lithium exchange, giving rise to the isoquinoline nucleus 304, via a Parham-... 

The reduction of the isoquinoline nucleus of compound 7 proceeded with high stereocontrol. What factors could be responsible for the selectivity ... 

Introduction of a suitable side chain into the 1-position of an isoquinoline and subsequent cyclisation on to the 8-position of the isoquinoline nucleus affords a route to benzo[d,e]quinoline. As an illustration, the isoquinolypropionic acid (80) with fuming sulphuric acid... 

The displacement of halogen at all positions of the pyridine and quinoline/isoquinoline nucleus is achievable using paUadium(O) catalysis (see 4.2 for a detailed discussion). Couplings with alkenes (Heck reac-... 

This alkaloid is monophenolic and on methylation with diazomethane gives rise to narcotine. Hydrolytic fission with dilute acetic acid yields meconin, and therefore the hydroxyl is in the isoquinoline nucleus and narcotoline is II (R = H). 

Ch. 1 Properties and Reactions of Isoquinolines and Their Hydrogenated Derivatives Ch. 2 Synthetic and Natoral Sources of the Isoquinoline Nucleus Ch. 3 Biosynthesis of Isoquinolines Ch. 4 Quaternary Isoquinolinium Salts... 

Although the Skraup/Doebner-von Miller reaction represents one of the most common reaction for the synthesis of quinoline core for more than a century, its mechanism is still dedebated. To date, both of the two more popular mechanistic explanations are involving fragmentation-recombination pathways. In the first one, initially the amine reacts with the aldehyde or ketone under acidic conditions to form an imine. Dimerization and Pictet-Spengler type cyclization forms a diazetine core. Protonation and subsequent cyclization-ring cleavage reaction assembles the isoquinoline nucleus. 

Several groups potentially capable of alkylation of the enzyme, ribonucleoside diphosphate reductase, were introduced at the 5-position of the isoquinoline nucleus of (1) in an effort to design possible irreversible inhibitors of the enzyme [42]. Two series of compounds were made using either 5-amino or 5-hydroxy derivatives as precursors of corresponding amides (81) [-NHS02Me,... 

Pyridones, such as 39 and 40, which bear a structural relationship to papaverine, have shown enhanced activity and/or duration of peripheral vasodilator activity in dogs. (- )-Trimetoquinol has more potent j8-adrenergic activity than its enantiomer in a variety of systems. The intact tetrahydro-isoquinoline nucleus appears to be necessary for the j8-adrenoceptor action of this synthetic diphenolic tetrahydrobenzylisoquinoline. ... 

In a similar attempt, Decker and Eichler reduced. -methylnor-papaverinium phenolbetaine (VIII) with tin and hydrochloric acid and obtained -laudanine, m.p. 112°, picrate, m.p. 162-8°, which was subsequently investigated by Spath and Epstein, who showed that on methylation it furnished dMaudanosine and that the ethyl ether on energetic oxidation yielded veratric acid (3 4-dimethoxybenzoic acid) and the methyl ethyl ether of wor-m-hemipinic acid. This clearly indicated that the free hydroxyl group was in the isoquinoline nucleus, and its position was determined by the fact that on mild oxidation 7-methoxy-6-ethoxy-l-keto-2-methyl-l 2 3 4-tetrahydrowoquinoline, m.p. 95-6°, was produced, and on this basis these authors assigned formula (IX R == H R = CH3) to laudanine. 

The position in which the veratryl residue is attached to this isoquinoline nucleus in papaveraldine and papaverine is determined by the formation of pyridine-2 3 4-tricarboxylic acid in the oxidation of papaverine by hot permanganate. On the basis of these results, Goldschmiedt assigned the following formula to papaveraldine —... 

The isoquinoline nucleus is widespread and well known in the alkaloid families with many biological and physiolc cal activities (02TL5089). These isoquinoline alkaloids (99TL793,00CEJ1017,99OL997,00OMl 123, 99JOM141) are believed to be biosynthesized from tyrosine. 

Microwave-assisted direct aiylation reactions were successfully employed in the synthesis of azafluoranthene alkaloids. Ponnala and Harding (2013) reported that direct aiylation reactions on a diverse set of phenyltetrahydroisoquinolines produced the indeno[l,2,3-ij]isoquinoline nucleus, required towards a high-yielding azafluoranthene synthesis. The method was used as a key step in the efficient preparation of the natural products rufescine and triclisine. This synthetic approach may be generally applicable to the preparation of natural and un-natural azafluoranthene alkaloids as well as azafluoranthene-like isoquinoline alkaloids. 

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