2- -1,2,3,4-tetrahydroiso

The intramolecular photoelimination of HC1 from JV-chloroacetyl derivatives of suitable amines is a useful and versatile approach to the synthesis of azaheterocycles. The iV-chloroacetyl derivative 357 has been converted in this way to 7-oxodesethylcatharanthine (358) in 55% yield.300 Investigations in this area have been particularly concerned with the A-chloroacetyl derivatives of benzylamines and phenethylamines the N-chloroacetyl-benzylamine 359 on irradiation affords the two 3-oxo-l,2,3,4-tetrahydroiso-quinolines 360 and 361.301 Competing photocyclizations have been observed in the case of l-[3-(chloroacetylamino)propyl]-3-methylindole (362) which is converted into three photoproducts, 363, 364, and 365.302... 

Substituted derivatives 219 were prepared from 1,2,3,4-tetrahydroiso-quinoline-l,4-dione 217 and sulfonyl ketene thioacetals 218. The same products were also obtained from 220 and 221 (Scheme 52) (79YZ1234). 

Enantioselective catalytic hydrogenation. The ruthenium(II) complexes of (R)- and (S)-l, bearing a chiral BINAP ligand, catalyze asymmetric hydrogenation of N-acyl-l-alkylidenetetrahydroisoquinolines to give (1R)- or (lS)-tetrahydroiso-quinolines in 95-100% ee.1 Thus the (Z)-enamide (2), prepared by acylation of 3,4-dihydropapaverine, is hydrogenated in the presence of (R)-l to (1R)-tetrahydroisoquinolines (3). The enantiomeric (lS)-3 is obtained on use of (S)-l as catalyst. 

The asymmetric alkynylation of isoquinoline iminium ion was reported in the presence of CuBr/QUINAP system (Scheme 5.7). ° Various alkynyl tetrahydroiso-quinolines were obtained in excellent yields and enantiomeric excesses. A natural product, homolaudanosine, was synthesized by the reduction of the obtained propargyl tetrahydroisoquinoline. 

Praziquantel Praziquantel, 2-(cyclcohexylcarbonyl)-l,2,3,6,7,llb-hexahydro-47f-pyrazino [2,la]isoquinolin-4-one (38.1.15), is a derivative of pyrazinoquinoline that is made in two ways [17-19], According to one of them, l-aminomethyl-l,2,3,4-tetrahydroiso-quinoline is alkylated with chloroacetic acid, and then the resulting amine is acylated with cyclohexanecarbonyl chloride to make l-(iV-carboxymethyl-iV-cyclohexylcarbonyl-aminomethyl)-l,2,3,4-tetra-hydroisoquinoline (38.1.14), which is heated at 150°C to give the desired praziquantel. 

Phenylethylamino alkaloids Simple tetrahydroiso quinoline alkaloids... 

Rommelspracher, H May, T. and Susilo, R. 1991. 3-Carbolines and tetrahydroiso-quinolines Detection and function in mammals. Planta Medica, 57 S85-S92. 

Consideration of the tetrahydroiso-a-acids depends on their precursors. They are manufactured commercially from, ultimately, either a- or /3-acids. The chromatogram of those from the a-acid route demonstrate a chromatographic profile similar in detail to conventional iso-a-acids, with similar ratios of stereoisomers. Those derived from /3-acids look quite different. Because the /3-acids are racemic, there is a random distribution of orientations about the two adjacent chiral centers, which in practice results in the two peaks of about equal area for each of the... 

The complexity of the tetrahydroiso-a-acids from /3-acids extends to the hexahydroiso-a-acids (also derived from /3-acids), with the added complication that borohydride reduction of a carbonyl to a carbinol moiety results in yet another racemic, optically active center, theoretically giving rise to eight hexahydroiso-a-acids for each of the co-, -, and ad-variants. This number of compounds has, as far as the author is aware, precluded the derivation of individual response factors for each of these compounds. Indeed, identification of all of the significant bands evident in a chromatogram of the hexahydroiso-a-acids has not yet been reported in the public domain. 

Excellent chromatographic performance using micellar electrokinetic chromatography (MEKC) has been demonstrated for the a-, / -, and iso-a-acids. Thus the six major components of a mixture of a- and /3-acids can be baseline resolved within 10 minutes (47). Similarly, the six major iso-a-acids can be baseline resolved within 20 minutes (48). De Keukeleire presented MEKC separations of the p- and tetrahydroiso-a-acids that compared well with conventional HPLC analyses (17). 

Verzele and de Keukeleire have reviewed the difficulties associated with the standardization of hop acid analyses (33). In particular, at the time of writing, standardization for isomerized and chemically modified components is highly topical. As mentioned earlier, the trans-iso-a-acids specifically precipitate when a mixture of iso-a-acids is treated with dicyclohexylamine, and it has recently been shown that this behavior extends to the hexahydro-, p-, and (with difficulty) tetrahydroiso-a-acids (55). An international subcommittee has recently been convened to establish standards for the full range of chemically modified iso-a-acids to encourage international standardization for ensuring beer quality control and to provide an agreed basis on which these products can be traded. 

JP Maye, S Mulqueen, S Weis, J Xu, M Priest. Preparation of isomerized ar-acid standards for HPLC analysis of iso-a-acids, rho-iso-ar-acids, tetrahydroiso-ar-acids and hocahydroiso-ar-acids. J Am Soc Brew Chem, 57 55-59, 1999. 

Unsymmetrical secondary and tertiary amines. Unsymmetrical amines are obtained in 50-95% yield by reaction of an alcohol and amine in the presence of this ruthenium catalyst. The intramolecular version of this reaction provides an efficient synthesis of cyclic amines either from oc,a>-amino alcohols and an alcohol or from a,tu-diols and an amine. The cyclization is useful for preparation of tetrahydroiso-quinolines.3... 

Reaction of 1 -(2-hydroxyethyl)-6,7-dimethoxy-l,2,3,4-tetrahydroiso-quinoline with 36% H2CO solution in MeOH at room temperature provided 9,10-dime thoxy-1,6,7,1 lb-tetrahyd ro-2/d,4/d-[l,3 Joxazino[4,3-flJ isoquinoline in 82% yield (09T8021). 

---