Isoquinoline-1-carboxylic acids, tetrahydro

Isoquinoline-1-carboxylic acid, tetrahydro- Decarboxylation Laccase, peroxidase 204... 

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. 

Reaction of 1,2,3,4-tetrahydro-6//-pyrimido [1,2-b]isoquinolin-6-one (116) and maleic acid in boiling ethanol afforded tetracyclic carboxylic acid 117 (88HCA77). 

Benzyl-6-oxoperhydropyrido[2,l-c][l,4]oxazine-4-carboxylic acid was prepared from the 7-unsubstituted derivative by alkylation with PhCH2Br in the presence of lithium bis(trimethylsilyl)amide in THF at -78°C (96MIP8). The reaction of 1,3, 4,6,7,116-hexahydro[l,4]thiazino[3,4-a]-isoquinolin-4-one (45) with a Vielsmeier-Haack reagent afforded 3-formyl-4-chloro-l,6,7,llh-tetrahydro[l,4]thiazino[3,4-a]isoquinoIine (111) (81CP 1101857). 

Treatment of 8-hydroxymethyl-l,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroquinoline-8-carboxylic acid, or l-(2-hydroxyethyl)-l,2,3,4-tetrahydroisoquinolines with COCI2 in the presence of a base furnished l,5,6,7-tetrahydro-3//-pyrido[3,2,l-(/ ][3,l]benzoxazin-3-one (92JMC1076), the -1,3-dione (102) (78JHC645), and l,2,4,6,7,llft-hexahydro[l,3]oxazino[4, 3-a]isoquinolin-4-ones (92T4937), respectively. 

Coutts IGC, Hamblin MR, Tinley EJ (1979) The enzymatic oxidation of phenolic tetrahydroiso-quinoline-1-carboxylic acids. J Chem Soc Perkin Trans 1 2744-2750 Davis VE, Cashaw JL, McMurtrey KD, Ruchirawat S, Nimit Y (1982) Metabolism of tetrahydro-isoquinolines and related alkaloids. In Bloom F, Barchas J, Sandler M, Usdin E (eds) Beta-carbolines and tetrahydroisoquinolines. Liss, New York, p 99 Furuya T, Nakano M, Yoshikawa T (1978) Biotransformation of (RS)-reticuline and morphinan alkaloids by cell cultures of Papaver somniferum. Phytochemistry 17 891-893 Gates M (1953) Conversion of codeinone to codeine. J Am Chem Soc 75 4340-4341 Graves JMH, Smith WK (1967) Transformation of pregnenolone and progesterone by cultured plant cells. Nature (London) 214 124 8-1249... 

Treatment of ethyl 10-(dimethylaminomethylene)-ll-cyano-4-oxo-7,8, 9,10-tetrahydro-4//-pyrimido[l,2-b]isoquinoline-3-carboxylate (119) with 2 N hydochloric acid at 20°C for 3 h afforded tetracyclic derivative 160 (84KFZ931). 

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