Analogues of Isoquinoline

Thiophene analogues of isoquinolines have also been synthesised through lithiation reaction... 

Thiophen Analogues of Isoquinoline. - Several derivatives of thienol3,2-c]pyridine, such as 4-allyl-5-methyl-4,5-dihydrothieno-... 

This reaction has been modified to occur in a solvent such as CHsCN and CH2Cl27 The synthesis of thiophene analogues of isoquinolines is another modification. ... 

The condensation of thiophen aldehydes with nitromethane to oj-nitro-vinylthiophens has been extensively used in connection with the synthesis of thiophen analogues of isoquinoline. The liquid-phase hydrogenation of o)-nitro-2-vinylthiophen over Pd-black to 2-thienylacetaldoxime has... 

Thiophen Analogues of Isoquinoline and Related Compounds.— During the past three years, interest in the synthesis, reactions, and physical properties of these compounds has been noticeable, and four different research groups have made important contributions to this field. Both thieno[2,3-c]-pyridine (548) and thieno[3,2-c]pyridine (549) have been prepared in a... 

Thiophen Analogues of Isoquinoline.—4,7-Dimethylthieno[2,3-c]pyridine has been synthesized by hydrolysing the acetal function of (252). This compound was obtained by the reaction of 2-(3-lithio-2-thienyl)-l,3-dioxolan with diacetyl followed by oximation and reduction. 6,7-Dimethylthieno[3,2-c]pyridine was obtained in an analogous manner, (2,5-Dimethyl-3-thienyl)acetone gave (253) on acylation. Treatment with perchloric acid gave the pyrylium salt (254), which upon reaction with NH3 gave (255). The same reaction sequence with (3-benzo-... 

The Pictet-Spengler reaction has been carried out on various solid support materials " and with microwave irradiation activation.Diverse structural analogues of (-)-Saframycin A have been prepared by carrying out the Pictet-Spengler isoquinoline synthesis on substrates attached to a polystyrene support. Amine 20 was condensed with aldehyde 21 followed by cyclization to give predominantly the cis isomer tetrahydroisoquinoline 22 which was further elaborated to (-)-Saframycin A analogues. 

Fluorination. Attention has been focused on the direct fluorination of isoquinolines activated by conversion into 2-methylisocarbostyril (80). With gaseous fluorine (diluted to 10% with argon) in acetic acid a 54% yield of the 4-fluoro derivative was obtained. (Scheme 40). With methylene chloride as the solvent, only the 4-chloro analogue was formed [82H( 17)429]. Fluoroisoquinolines have also been made by displacement of nitro groups, and from diazonium fluoroborates (87JHC181). Hepta-chloroisoquinoline was converted into a perfluoro derivative by heating it in an autoclave with anhydrous potassium fluoride [66JCS(C)2328]. 

The HMO method has been used to study models of all the aza analogues of pyridine, quinoline, isoquinoline, the monoazaanthra-cenes, and 1- and 9-azaphenanthrenes as well as of their derivatives such as aminopyridines and aminoquinolines.28 Again their energy characteristics are correlated with those of the parent systems. 

The 13C spectrum of emetine (112) (Fig. 23 and Table XXII) was examined by Wenkert and co-workers (69). The chemical shift assignments were made by comparison with the shifts recorded for the simple isoquinolines and pro-toberberine alkaloids such as tetrahydropalmatine (69) (6, 14), and with indolic analogues of emetine (69). The shifts of C-4 and C-6 are characteristic of a trans-quinolizidine conformation for this ring system by analogy... 

Axially chiral bis-isoquinoline N,N -bisoxide (S)-17 has been reported to promote the addition of Me3SiCN (1.5-2.0 equiv.) to imines 78, derived from aromatic aldehydes (Scheme 7.17) here, CH2CI2 was identified as an optimal solvent. The reaction is stoichiometric in 17, and exhibits partial dependence on the imine electronics (62-78% ee), but much less than that observed for the allylation of PhCHO catalyzed by QINOX (24) (vide supra). The o-substitution had a positive effect in the case of Cl (95% ee), but a very negative effect in the instance of MeO (12% ee). Chelation of the silicon by the N-oxide groups was suggested to account for the stereochemical outcome. Analogues of 17 were much less successful [75]. 

Diels-Alder addition of azadienes to quinones has been used to prepare analogues of the antibiotic diazaquinomycin (26). Quinoline-5,6-quinone yields both regioisomers (Equation (8)) while the isoquinoline quinone gives only the pyrido[3,4- ]quinoline (79) (Equation (9)) <91TL1307>. 

Later steps of biosynthesis follow as the joining together of (22) with a tyrosine-derived molecule to give the amino-acid (23), analogues of which are involved in isoquinoline biosynthesis.40 Appropriate oxidative phenol coupling41 and subsequent steps as indicated (Scheme 5) could afford tylophorine (17) and tylophorinine (24).39... 

The discovery of the anthelmintic activity of the pyrazinoisoquinolines [25,31,32] initiated the synthesis of a variety of substituted pyrazinoisoquinolines. Praziquantel was picked up from more than 400 l,2,3,6,7,llb-hexahydro-4H-pyraz-ino[2,l-a]isoquinolin-4-ones and related compounds, because of its potent and broad spectrum biological activity [26]. The structure activity relationship in the analogues of praziquantel would indicate that positions 2 and 4 are the most critical positions, which govern the cestodicidal as well as antischistosomal activities in the pyrazinoisoquinolines. 

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