3- methyl-l,2,3,4-tetrahydroisoquinolines

Treatment of (11 aS)-3-isopropyl-11 a-methyl-4-phenyl-1,6,11,11 a-tetrahy-dro[l,4]oxazino[4,3-6]isoquinolin-l-one (243) with 6N HCl in a pressure tube, then the reaction of the work-up residue with propylene oxide gave (3S)-3-methyl-l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (244) (99S704). 

A 6,6-dimethyl-6,7-dihydropyrido[l,2-c]quinazolinium salt was obtained from the reaction of 2-(2-aminophenyl)-pyridine and acetone <1997AJC109>. Reaction of 3-methyl-l,2,3,4-tetrahydroisoquinoline-l-acetamides 195 (R = H) with 36% aqueous CH20 gave 1,3,4,6,7,11 b-hcxahydro-2//-pyrirmido[6,1 - ]isoquinolin-2-oncs 153 and their 3-methyl derivatives <1997LA1165>. When the reaction was carried out in the presence of 37% aqueous NaOH, 3-hydroxymethyl derivatives 152 were obtained. Reactions with PhCHO were stereospecific affording only diastereomers 196 (Equation 41). 

Mangas-Sanchez, f., Busto, E., Gotor-Fernandez, V., and Gotor, V. (2012) Enantiopure 3-methyl-3,4-dihydroisocoumarins and 3-methyl-l,2,3,4-tetrahydroisoquinolines via chemoenzymatic asymmetric transformations. Catal. Sci. Technol., 2 (8), 1590-1595. 

To a two-neck 50 mL round-bottom flask was added 6,7-dimethoxy-l-methyl-l,2,3,4-tetrahydroisoquinoline (3.093 g, 14.92 mmol), C. rugosa lipase (1.5 g, 1410 units/mg), pentamethylcyclopentadienyliridium(III) iodide (34.3 mg, 0.030 mmol) and toluene saturated with water (25 mL), resulting in an orange solution containing some insoluble amine. 

A number of nonnatural amino acids were resolved into individual enantiomers on 0-9-(2,6-diisopropylphenylcarbamoyl)quinine-based CSPby Peter and coworkers [48,90,113,114] after derivatization with Sanger s reagent, chloroformates (DNZ-Cl, FMOC-Cl, Z-Cl), Boc-anhydride, or acyl chlorides (DNB-Cl, Ac-Cl, Bz-Cl). For example, the four stereoisomers of P-methylphenylalanine, P-methyltyrosine, P-methyltryptophan, and P-methyl-l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid could be conveniently resolved as various A-derivatives [113]. The applicability spectrum of cinchonan carbamate CSPs comprises also P-amino carboxylic acid derivatives, which were, for example, investigated by Peter et al. [114]. A common trend in terms of elution order of DNP-derivatized P-amino acids was obeyed in the latter study On the utilized quinine carbamate-based CSP, the elution order was S before R for 2-aminobutyric acid, while it was R before S for the 3-amino acids having branched R substituents such as wo-butyl, iec-butyl, tert-butyl, cyclohexyl, or phenyl residues. 

According to polarity alternation the acceptor substituted benzenes should also undergo ipso substitutions [12] Indeed such reactions occur when A = SiMe3, SnRj, HgR. A useful application of the silyl group as site determinant is found in a synthesis of 8-methoxy-iV-methyl-l,2,3,4-tetrahydroisoquinoline [13]. The donor character at the ortho position of the methoxy function is accentuated and steric disfavor is overcome. 

Stereocontrolled synthesis of W-methyl-l,2,3,4-tetrahydroisoquinoline derivatives using chromium tricarbonyl 90JOM(400)223. 

Alkaloid isolations and structural elucidations are summarized in Table 3. Reduction of a new quaternary alkaloid isolated from Berberis oblonga gave 6-hydroxy-7-methoxy-2-methyl-l,2,3,4-tetrahydroisoquinoline and the alkaloid was deduced to... 

Naoi, M., Matsuura, S., Parvez, H., Takahashi, T., Hirata, Y., Minami, M. and Nagatsu, T. (1989a) Oxidation of N-methyl-l,2,3,4-tetrahydroisoquinoline into the A-methyl-isoquinolinium ion by monoamine oxidase. J. Neurochem. 52 653-655. 

Recently Kondo, Tomita, and Uyeo (55) applied the technique of chromatographic adsorption on alumina to the separation of the alkaloids of Cissampelos insularis Makino and Stephania cepharantha. By this means they isolated, in addition to those known, a new, crystalline, ether-soluble alkaloid whose analysis agreed with that of a bisbenzylisoquinoline alkaloid. This same alkaloid was also found in Chondodendron tomentosum (104) and Stephania capitata Spreng (121). Through a comparison of its properties and that of its derivatives with samples of isochondodendrine dimethyl ether and derivatives provided by Faltis, the Japanese workers (55) established the structure of the new alkaloid as being fully methylated isochondodendrine (LXI). They suggested the names methylisochondodendrine or cycleanine. An attempt to synthesize this alkaloid was not successful (130). Hovrever, by means of sodium and liquid ammonia the compound has been bisected into only one phenolic base whose structure proved to be M-(4 -hydroxybenzyl)-6,7-dimethoxy-iV-methyl-l,2,3,4-tetrahydroisoquinoline (134). This showed that cycleanine (methylisochondodendrine) has the structure (LXI) with both the asymmetric centers levorotatory. 

A formal [3-I-3]-cycloaddition of azomethine ylide derived from sarcosine and formaldehyde with benzaldehydes has been reported to give 5-aryloxazolidines which rearrange to 2-methyl-l,2,3,4-tetrahydroisoquinolin-4-ols on heating with hydrochloric acid (Scheme 63). ... 

Procedure 3 Dynamic Kinetic Resolution of 6,7-Dimethoxy-l-methyl-1,2,3,4-tetrahydroisoquinoline... 

Antkiewicz-Michaluk L, Wardas J, Michaluk J, Protective effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline against dopaminergic neurodegeneration in the extrapyramidal structures produced by intracerebral injection of rotenone, Int J Neuropsychopharmacology 7 153-163, 2004. 

Racemic, cyclic and open-chain 1,2-diarylalkanes have been deprotonated under the regime of the sparteine protocoP . )V-Methyl-4-phenyl-l,2,3,4-tetrahydroisoquinoline (276) was deprotonated by i-BuLi/(—)-sparteine (11) and the intermediates 277 were quenched by MeOD. When performing the reaction in diethyl ether, (R)-278 was isolated with high ee values, up to 88% (equation 68). ... 

The geometric isomers 464 and 467 of 5(47/)-oxazolones prepared from acetophenones can be separated. Alternatively, the mixture can be isomerized under the appropriate reaction conditions to obtain the pure of (Z) or ) isomer. Each isomer can be converted to a pair of enantiomers 466 and 469 (only one enantiomer shown) (Scheme 7.152). The p-methyl phenylalanine analogues thus obtained are constrained phenylalanines and the effect of incorporation of a p-MePhe or p-MeTyr residue on the biological properties of H-Tyr-Tic-Phe-Phe-NH2 (TIPP, where Tic = l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) a delta opioid receptor antagonist, has been studied. ... 

Ueno et al. 15 reacted l,4-dioxo-l,2,3,4-tetrahydroisoquinoline (406) with carbon disulfide, then methylated to 407, which, with DMAD and potassium carbonate in DMF, gave dimethyl 6,11-dioxo-l-methylthio-3,4, 6,1 l-tetrahydro[l, 4]thiazino[4,3-6]isoquinoline-3,4-dicarboxylate (408). 

Noscapine (Nectadon ), 2-methyl-8-methoxy-6,7-methylenedioxy-l-(6,7-di-methoxy-3-phtha-lidyl)-l,2,3,4-tetrahydroisoquinoline, is also one of the isoquinoline derivatives present in opium. Next to morphine, it is the most abundant of the opium alkaloids, present to the extent of 6% in the seed capsules. This drug was formerly known as narcotine but, because it is neither chemically nor pharmacologically related to the narcotics, is more appropriately designated as noscapine. 

The thermal condensation of p-benzyloxyphenylacetic acid and of 3-methoxy-4-hydroxyphenethylamine occurs and gives, with a yield of 86% to 92%, the N-(3-methoxy-4-hydroxyphenethyl-p-benzyloxyphenyl)acetamide from this latter, by cyclization according to Bischler-Napieralski with phosphorus oxychloride in acetonitrile, followed by reduction with sodium borohydride, there is obtained with a yield of 75% to 80% the l-(p-benzyloxybenzyl)-6-methoxy-7-hydroxy-l,2,3,4-tetrahydroisoquinoline, which is methylated with... 

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