Isoquinolone alkaloids

R = H). Bromination gave the 4-bromo-derivative which afforded (16 R = CN) and (16 R = CHO) by successive cyanization and Raney nickel reduction/ The reported synthesis of the isoquinolone alkaloid thalactamine from 2,3.4-trimethoxyphenethylamine is unexceptional but an alternative synthesis involving bromination of 6,7-dimethoxy-2-methyl-l(2//)-isoquinolone followed by methan-nolysis in methanolic sodium methoxide is somewhat surprising/ A number of new methods for preparing AT-substituted l(2//)-isoquinolones include reaction of homophthalic acids with Vilsmeier reagentand borohydride reduction of homophthalimides. The effect of various substituents on the fluorescence of such isoquinolones has been studied. 

Isoquinolone alkaloids are a group of naturally occurring alkaloids mainly isolated from Hernandiaceae and Ranunculaceae. They can be subdivided into two categories those with a totally aromatic nucleus, such as 6,7-dimethoxy-2-methylisocar-bostyril (43 a) [25] and doryanine (43b) [26], and those with a C3-C4 single bond, includingN-methylcorydaldine (45a) and oxyhydrastinine (45b) (Scheme 11) [27]. 

Hostalkova A, Novak Z, Pour M, Jirosova A, Opletal L, Kunes J, et al. Berfaanine A new isoquinoline-isoquinolone alkaloid from Berberis vulgaris (Berberidaceae). Nat Prod Commun 2013 8(4) 441-2. 

It has been indicated that isoquinolone alkaloids originate in plants from oxidation of simple benzylisoquinolines. A parallel assumption is that hernan-daline is formed by oxidation of a thalicarpine-type aporphine-benzyliso-quinoline. It is self-evident from the structure of baluchistanamine that in vivo oxidation of an oxyacanthine type alkaloid to an isoquinolone-benzyliso-quinoline dimer, as well as of a simple monomeric benzylisoquinoline to an isoquinolone, is an intrinsic feature of the alkaloidal catabolic process within B. baluchistanica. 

Enamines of cyclohexylamine have been enantioselectively cyclized to bicyclo[3.3.1] nonanedione systems, using acryloyl chloride and chiral pyrrolidine catalysis. Enantio-pure A-sulflnylimines have been used in asymmetric synthesis of isoquinolone alkaloids, and a stereocontrolled synthesis of 3,4,5,6-tetrahydropyrimidine-based amino acids from imino ethers has been reported. Diastereoselective additions of chiral acetals of (2-lithiophenyl)acetaldehyde to arylimines have been used in an asymmetric synthesis of 1-aryltetrahydroisoquinolines. " Organolithiums react with chiral imines, in the presence of Lewis acids or bases, to give amines in up to 100% de. Diastereoselective additions of copper reagents to imines derived from (5)-l-phenylethylamine have been reported. 

Hussain SF, Nakkady S, Khan L, Shamma M (1983b) Oxyhydrastinine, an isoquinolone alkaloid from the Papaveraceae. Phytochemistry 22 319-320 lee IR, Lee MM (1982) Studies of chemical constituents of the genus Thalictrum in Korea I. Alkaloids from the root of Thalictrum uchiyamai Nakai. Saegyate Hakhoe Chi 13 132-135, CA 98 221674y... 

Kapadia G, Fayez MBE (1973) The chemistry of peyote alkaloids. Lloydia 36 9-35 Krane BD, Shamma M (1982) The isoquinolone alkaloids. J Nat Prod 45 377-384 Kunitomo J-I, Murakami Y, Oshikata M, Shingu T, Lu S-T, Chen I-S, Akasu M (1981) The alkaloids of Stephania sasakii Hayata (13). On the tertiary minor bases. Yakugaku Zasshi 101 431-436... 

The reaction is essentially that described by the submitters.8 The procedure illustrates a convenient method for the synthesis of a type of lactone which could serve as an important intermediate in the synthesis of isoquinolones, tetrahydroisoquinolines, and isoquinoline alkaloids Several analogous and closely related lactones have been reported. 

The parent, unsubstituted isochromanone has been caused to react with a variety of aromatic amines to prepare Ar-substituted 1,4-dihydro-3(2.ff)-isoquinolones,4 and with amines to give amides.5 The 6,7-methylenedioxy-3-isochromanone was an intermediate in the synthesis of protopine and its allied alkaloids,6 and for the synthesis of the berberine ring system.7 The 6-methoxy analog was prepared as a potential intermediate in a camptothecin synthesis8 and 8-methoxy-4,5,6,7-tetramethyl-3-isochromanonc was an intermediate in the synthesis of sclerin.9 The compound herein described was the basis of a facile synthesis of ( l )-xylopmins,10 and its reaction with hydrazine has been reported.11... 

More than 55 alkaloids have been isolated from peyote. Mescaline (3,4,5-trimethoxy-j8-phenethylamine) is the primary psychoactive alkaloid of the peyote cactus, and by far the one that has been most studied (figure 9.6). These may be categorized into phenethylamines (including mescaline), isoquinolones, and Krebs acid conjugates. See table 9.2 for a partial list of peyote alkaloids. 

A novel route to ( )-0-methylthalisopavine (26) involves the oxidation of the properly substituted tetrahydro-3-isoquinolone of type 129 with vanadium oxy-trifluoride to furnish bridged lactam 130. Compound 130 was then reduced to the racemic isopavine alkaloid 26 in an overall yield of 4.4% (Scheme 26) 136). 

Thalistyline, a monoquaternary salt from the quaternary fraction of the chloroform-soluble alkaloids of Thalictrum longistylum and T. podocarpum, has strong hypotensive action at 1.0 mg kg-1 in normotensive dogs and rabbits. It has the structure (46), and both the related bis-tertiary base and bis-quaternary salt have been isolated in small quantities from the same plants.61 The structure of (46) was determined by its fission with sodium in liquid ammonia to form the bases (47) and (48), and by its oxidation to the isoquinolone (49) and the acid (50) when it reacted with potassium permanganate.61... 

Davis and Andermichael recently described a new method for the asymmetric synthesis of 3-substituted-1 -(2//)-isoquinolones which are important chiral building blocks for alkaloid synthesis.83 This procedure involved the highly diastereose-... 

Similarly, application to the chemistry of isoquinoline alkaloids allowed the preparation of a 1-isoquinolone derivative in good yield from the corresponding enamine30 (Scheme 16). 

Narciclasic aldehyde (16 R = CHO), a key degradation product in the structural elucidation of the alkaloid narciclasine, has been synthesized via the isoquinolone... 

T. sultanabadense Stapf., a small plant that grows under the shade of rocks on the rocky mountain slopes of eastern Turkey, is a source of the dimeric bisbenzylisoquinoline alkaloids thalbadensine, hemandezine, and thalictine, and the monomeric alkaloids thalifoline (isoquinolone), berberine (protoberberine), and magnoflorine (aporphine). 

Oxidation of bisbenzylisoquinoline alkaloids with potassium permanganate has been found to be controllable enough to permit fission of only one of the two benzylisoquinoline systems. In this way the O-acetyl derivatives of the isomeric alkaloids tiliacorine and dinklacorine have been oxidised to the aldehydo-isoquinolones (67, R =Me, R =Ac) and (67, R =Ac,R =Me) respectively (Shamma and J.E. Foy, J.org.Chem., 1976, 1293 ... 

Phthalides are valuable synthons for obtaining several biologically active compounds and natural products. Naphthols, anthraquinones and anthraquinone antibiotics, isoquinolones, phthalide isoquinolines, indolizidine and quinolizidine alkaloids, and berbine alkaloids have been synthesised with phthalides as the starting compounds. Some of the syntheses, which have interesting chemistry, are described below. The required phthalides, in some cases, have been synthesised through aromatic lithiation reactions, while in others by more conventional methods. 

Homophthalic anhydrides are valuable synthons for the synthesis of isocoumarins, isoquinolones and particularly for several berbine alkaloids. 

Various isoquinolines and isoquinoline alkaloids are easily available from isoquinolones... 

Particularly, isoquinolonic acids are useful precursors for the total synthesis of naturally occurring phenanthridine alkaloids such as corynoUne, oxocorynoline, and epicorynoline as well as indenoisoquinolines possessing sigiuflcant antitumor activity. 

Benzylisoquinoline plays an important role as a biosynthesis centre for Annonaceous alkaloids such as isoquinolones, protoberberines,... 

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