Tetrahydroisoquinoline-l-carboxylic acid

Tetrahydroisoquinoline-l-carboxylic acids have been anodically decarboxylated in MeOH-NaOMe on a graphite felt anode, giving 3,4-di-hydroisoquinolines (50-90%)417 This may be an example of a pseudo-Kolbe reaction in support of Hahn s theory of the biosynthesis of isoquinoline alkaloids by providing a laboratory analogy for the crucial decarboxylation step. 

The dipole stereochemistry is sensitive to both structural change in the a-amino acids and aldehydes, and reaction temperature (87CC49). The reaction of 1,2,3,4-tetrahydroisoquinoline-l-carboxylic acid with benzaldehyde and Af-methylmaleimide gives a 1 1 mixture of the maleimide cycloadducts 244 and 245 of anti- and syn-dipoles 242 at 120°Cin DMF(1 hr), and a 2.7 1 mixture at 21°C in the same solvent (120 hr). Because MNDO calculations on the related anti- and syn-ylides 240 show that syn-240 is 1.8 kcal/mol more stable than anti-240, the preference of the anti-ylide cycloadducts 245 must be a kinetic result. 

Kolbe reactions of heterocyclic compounds have been studied in only a few cases. Anodic oxidation of l-azabicyclo[2.2.2]octane-2-carboxylic acid under Kolbe conditions produced 2-methoxy-l-azabicyclo[2.2.2]octane [454]. The primary radical, formed by loss of an electron from the carboxylate ion, decarboxylates and is oxidized further to a carboca-tion, which is attacked by a methoxide ion. A similar pseudo-Kolbe reaction is found in the anodic decarboxylation of 1,2,3,4-tetrahydroisoquinoline-l-carboxylic acid derivatives to 3,4-dihydroisoquinolines [455]. 

TABLE 4.3. REACTIONS OF TETRAHYDROISOQUINOLINE-l-CARBOXYLIC ACIDS WITH TRIFLUOROACETIC ANHYDRIDE... 

Brossi A. Mammalian alkaloids conversion of tetrahydroisoquinoline-l-carboxylic acids derived from dopamine. Planta Med 1991 57 S93-S100. 

The Y keto acid (22) has been converted to acetate (23) in 67 % yield by electrolysis in a mixture of acetic acid, butanol, and triethylamine. Dihydroisoquino-lines (24) have been synthesized from tetrahydroisoquinoline-l-carboxylic acids in 50—90% yields, by oxidative electrochemical decarboxylation. 

Tetrahydroisoquinolines bearing a chiral center at the Cl position constitute a structural motif found in many biologically active compounds. For instance, (5)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-l-carboxylic acid 114 is a precursor of the natural product (5)-calycotomine (Scheme 57.31). Kanerva, Fiilbp, et al. have described the preparation of both enantiomers of 114 by enzymatic hydrolysis of the ethyl ester derivative rac-113. Considering this substrate undergoes spontaneous racemization in an aqueous medium, these authors carried out an exhaustive study of the reaction variables in order to find the optimal conditions and thus achieve the DKR of this substrate. Two enzymes with opposite enantiopreferences were used CAL-B and... 

Implication of the same type of intermediate (342 X = H) allows the rationaUzation of the acid-catalyzed decarboxylation of 1,2,3,4-tetrahydro-j8-carboline-l-carboxylic acids. As is stated in Section III,A,1, a, the tetrahydroisoquinoline-1-carboxylic acids and a-amino acids of analogous structure are converted into the corresponding... 

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). 

Ugi five-center three-component reaction of pipecolinic acid and glycol aldehyde dimer with isocyanides gave a 1 1.7-2.1 diastereomeric mixture of l-oxoperhydropyrido[2,Tc][l,4]oxazine-9-carboxamides 397 (Scheme 35) <20010L4149>. Using CF3CH2OH as solvent is critical for the reaction. When 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid was employed, 1,3,4,6,11,11 a-hexahydro-[ l,4]oxazino[4,3+]isoquinoline-4-carboxarnide was formed. 

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. 

Brossi, A. 1991. Mammalian alkaloids Conversion of tetrahydroisoquinoline-1-carboxylic acids derived from Dopamine. Planta Medica, 57 S93-S100 and, Xe, X. S., Tadic, D Brzostowska, M Brossi, A., Bell, M. and Creveling, C. 1991. Mammalian alkaloids - Synthesis and O-methylation of (S)-3 -hydroxycoclaurine and R-3 -hydroxycoclaurine and their N-methylated analogs with S-adenosyl-L-[methyl-C-14]methionine in presence of mammalian catechol O-methyltransferase. Helvetica Chimica Acta, 74 1399-1411. 

Completion of the synthesis of quinapril involves amide bond formation between 26 and a tetrahydroisoquinoline fragment. Two complementary protected 1,2,3,4-tetrahydro-3-isoquinoline subunits 27 and 28, each available in a single step from commercially available (6)-l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, were utilized (Scheme 10.7). Coupling with 26 using DCC and HOBt in dichloromethane afforded the penultimate compounds 29 and 30 as maleate salts. Cleavage of the f-butyl ester of 29 and treatment with HCl provided quinapril. Alternatively, hydrogenation of 30 under standard conditions cleanly removed the benzyl ester, and quinapril (3) was isolated after formation of the hydrochloride salt. 

Likewise, a wide range of complex polycyclic systems was constructed from suitable precursors. Compounds 269 and 270 were synthesized in 79% yield in a 1.6 1 ratio from tetrahydroisoquinoline-1-carboxylic acid, while 271 was obtained as a single stereoisomer in 87% yield from tetrahydro-p-carboline-l-carboxylic acid (Scheme 3.91). 

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. ... 

A series of l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives 16 (Scheme 10) as inducers of p-turns has also been described. 70 ... 

Reaction of tetrahydroisoquinoline-3-carboxylic acid 434 with primary amines and isonitriles provided 1,2,3,4, 1,11 -hexahydro-6H-pyrazino [l,2-b]isoquinolin-l-ones 435 (06HEC107). 

The catalytic and chiral efficiency of (S,S)-le was also appreciated in the asymmetric synthesis of isoquinoline derivatives, which are important conformationally constrained a-amino acids. Treatment of 2 with a,a -dibromo-o-xylene under liquid-liquid phase-transfer conditions in the presence of (S,S)-le showed complete consumption ofthe starting Schiffbase. Imine hydrolysis and subsequent treatment with an excess amount of NaHCOs facilitated intramolecular ring closure to give 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid tert-butyl ester 38 in 82% yield with 98% ee. A variety of l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives possessing different aromatic substituents, such as 39 and 40, can be conveniently prepared in a similar manner, with excellent enantioselectivity (Scheme 5.20) [25]. 

Epimers of 3-methylperhydropyrido[2,l-c][l,4]oxazine (189) were prepared by oxymercuration-demercuration of l-(3-propenyl)-2-hydroxy-methylpiperidine (188) [93JCR(M)1620, 93JCR(S)251]. Asymmetric bro-molactonization of optically active tetrahydroisoquinoline-3-carboxylic acid 190 gave a 5 1 mixture of l,3,4,6,ll,lla-hexahydro[l,4]oxazino[4,3-6]-isoquinoline-l,4-diones (191) and (192) (77CL1109 79T2345). 

Boc-D-7-hydroxy-l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid was dissolved in THF containing benzotriazol-l-yl-oxy-tris-(dimethylamino)phosphonium hexafluorophosphate and triethylamine and heated with the Step 1 product until amidation was completed. Thereafter, the coupled product was isolated. 

Tetrahydroisoquinoline-3-carboxylic acids, which can readily be obtained from L-dopa (110) with aldehydes, do occur in plants (748,749), but... 

Chen et al. reported a more environmentally friendly version of the Pictet-Spengler reaction <06H1651>. In this report, a series of 2-phenylsulfonyl-l,2,3,4-tetrahydroisoquinoline-1-carboxylic acid ethyl ester derivatives 114 were synthesized in good yields through the cyclization of A-phenylsulfonyl-P-phenethylamines 115 with a-acyl sulfide 116 using phenyliodine(III) bis(trifluoroacetate) (PIFA) in ionic liquid ([bminjPFJ. The use of the ionic liquid allows for a simple purification and [bmin]PF can conveniently be recycled. 

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