Isoquinolones, structure

Recent patent disclosures reveal efforts to optimize within this template. The amide moiety has been cyclized to give dihydroisoquinolone inhibitors such as 9 and 10 [57]. Using various mono- and bicyclic core structure scaffolds, the amide has also been constrained in isoquinolone,... 

In the course of synthetic work related to laudanosine, which is a 1 -benzyl-3 (2tf)-isoquinolinone, it appeared that four prototropic isomers are possible (72JHC853), demonstrating the complexity of the problem. According to the author, the 3-isoquinolone tautomer (4a) with the o-quinonoid structure predominates over the hydroxy form (4b), and the... 

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... 

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

Over the last seventy years over sixty species of Aristolochia have been exploited for chemical examination by research groups throughout the world and a variety of compounds have been isolated. The spectrum of physiologically-active metabolites from Aristolochia species covers 14 major groups based on structure aristolochic acid derivatives, aporphines, amides, benzylisoquinolines, isoquinolones, chlorophylls, terpenoids, lignans, biphenyl ethers, flavonoids, tetralones, benzenoids, steroids, and miscellaneous. The aristolochic acid derivatives, host of phenanthrene derived metabolites were further classified into aristolochic acids, sodium salts of aristolochic acids, aristolochic acid alkyl esters, sesqui- and diterpenoid esters of aristolochic acids, aristolactams, denitroaristolochic acids, and aristolactones. The terpenoids can further be subdivided into 4 groups mono-, sesqui-, di- and tetraterpenoids. 

In 3-oxy-isoquinoline there is an interesting and instructive situation here the two tautomers are of comparable stability. 3-Isoquinolinol is dominant in dry ether solution, 3-isoquinolone is dominant in aqueous solution. A colourless ether solution of 3-isoquinolinol turns yellow on addition of a little methanol because of the production of some of the carbonyl tautomer. The similar stabilities is the consequence of the balancing of two opposing tendencies the presence of an amide unit in 3-isoquinolone forces the benzene ring into a less favoured quinoid structure, conversely, the complete benzene ring in isoquinolinol necessarily means loss of the amide unit and its contribution to stability. One may contrast this with 1-isoquinolone which has an amide, as well as a complete benzene, unit. ... 

The isoquinolone doryanine (4) has been isolated from Doryhora sassafras, and its structure has been confirmed by synthesis from methylenedioxyhomophthalic anhydride."... 

The structure of magnolamine has been revised to (45) following spectroscopic studies and the oxidation of magnolamine triethyl ether to the isoquinolone (46) and the dicarboxylic acid (47). ... 

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. 

Most of the alkaloids containing an isoquinoline structure that are considered are presented in the following order simple iso quinolines, isoquinolones, and phenethylammonium compounds benzyltetrahydroi-soquinolines bisbenzylisoquinolines and bisbenzyltetrahydroisoquino-lines protoberberines and tetrahydroprotoberberines proaporphines aporphinoids dehydroaporphines 7-substituted aporphines oxoapor-phines phenanthrenes miscellaneous isoquinohne-type alkaloids and nonisoquinoline alkaloids. 

A, B, and C were isolated and their structure confirmed by X-ray crystallographic analysis of their single crystals. First, the in situ generated ruthenium acetate catalyst reacts with isoquinolone to form the five-membered ruthenacycle A by an acetate-assisted deprotonation mechanism. Then, the alkyne insertion into the Ru-C bond affords a seven-membered ruthenacycle intermediate B. After the reductive elimination from B forming the C-N bond, a Ru(0) intermediate C was generated. Finally, the desired product was obtained from the decoordination of a Ru(0) species which regenerated the active Ru(OAc)2(p-cymene) initial complex on oxidation with copper acetate (Scheme 19) [185]. 

Isoquinolones of the simple type may also be included in this general group of alkaloids, because of the structural similarity. Biosynthetically, however, these compounds are probably degradation products of more complex isoquinoline alkaloids, as has been pointed out in recent reviews (Lundstrbm 1983, Krane and Shamma 1982). 

The isoquinolones form a distinct group of alkaloids. Thirteen different compounds of the monomeric type (Fig. 3) are presently known (Krane and Shamma 1982, Lundstrom 1983). Three dimeric structures are also known, but these are not further treated in this presentation. 

The isoquinolone siamine found in the Caesalpiniaceae plant Cassia siamea has an oxygenation pattern clearly different from other isoquinolones and also carries a methyl substituent at carbon-3. This compound is probably not derived from an aromatic amino acid but rather from structurally related polyketides that occur in the same plant (Ahn et al. 1978). 

As described in this chapter, transition-metal catalysts promote various types of cyclization reactions between C=N, C=0, N—H, O—H, and S—H bonds and alkynes in 5/6-endo/exo-dig manners. These reaction modes provide facile and atom-economical pathways to aromatic compounds such as pyrroles, indoles, isoquinolines, quinolines, furans, thiophenes, oxazoles, pyrones, and isoquinolones and their aza analogs and fused-ring congeners. Particularly notable is their utility in cascade reactions, which are step-economical approaches to target molecules, which increase rapidly in structural complexity. Therefore, these reactions can help provide solutions to meet the increasing demands of environmentally benign synthesis in modern organic chemistry. 

Indole and isoquinolone nuclei are prominent structural units frequently found in numerous natural products and pharmaceutically active compounds. Thus, the search for new methodologies to obtain these scaffolds with different substitution patterns is a current major objective in organic synthesis. Similar to benzofuran synthesis, Aluraez et al. observed that the palladium-catalyzed cascade intramolecular alkyne aminopaUadation/intermolecular Heck-type coupling reaction under oxidative conditions is an efficient methodology for the synthesis of indole 217 and isoquinolone 219 derivatives, starting from readily available aniline 216 or benzamide 218 substrates and functional alkenes [77] (Scheme 6.60). 

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