Reaction of isoquinolines with (R)-menthyl chlorocarbonate or (S)-α-Cbz-aminoacyl fluorides and arenes or heteroarenes gave access to 2-acyl-1-aryl-1,2-dihydroisoquinolines in a Mannichtype reaction via intermediate N-acylisoquinolinium salts. As an alternative, aryl metal compounds could be used. Modest stereoselectivities were achieved. Further reduction and hydrolysis of the products gave access to 1-aryl-1,2,3,4-tetrahydroisoquinolines.
Reissert compounds 2 derived from isoquinoline, chloroformates and TMS-cyanide were alkylated in position 1. The resulting alkylation products 3 as well as the precursors 2 reacted with Grignard reagents affording imidazoisoquinolines 4, 5, 7 and 8 by addition to the cyano group and Grignard reduction or by twofold addition to the cyano group, respectively. In both cases the alcohol of the 2-alkoxycarbonyl moiety was eliminated by attack of the N-atom at the carbonyl carbon atom. Under acid conditions, 1-benzylated Reissert compound 3h cyclised by attack of the resulting N-acyliminium C-atom at the o-position of the benzyl ring to form tetracyclic 1,3-bridged tetrahydroisoquinolines 10 and 11. Bromocyclisation of 1-allyl-2-menthyloxycarbonyl-substituted Reissert compounds 3b, c led to tricyclic dibromo products 12, in which the menthol moiety was split off and addition to the enamine double bond occurred. A 2-menthyloxycarbonyl group in Reissert compounds 2a and 3 failed to exert an asymmetric induction in all cases.
Anellated 1-azabicyclo[3.3.1]nonanes 6 were synthesized by several routes starting from natural α-amino esters 2 and ohaloaryl-or o-bromohetarylmethyl bromides 1. N-Alkylation of the starting amino esters to 5 and 3 was followed by halogen/lithium exchange and double cyclization. The cyclization products 6 exhibit interesting inhibition of RNase H and
Activity. -The synthesis of optically active anellated azabicyclo[3.3.1]nonanes (IV) and (XI) is readily achieved by halogen/ lithium exchange and subsequent double cyclization of bis(α-hetarylmethyl)amino esters (III) and (X), resp., which in turn are obtained on various ways from o-bromohetarylmethyl bromides (I) and optically active amino acid esters (II). The cyclization is influenced by the steric bulk of the reactants and in some cases only the monocyclization products (VI)/(VII) or (XII) are achieved. The double cyclization products possess interesting inhibiting activity against reverse transcriptase and DNA polymerase of HIV-1. -(FALTZ, H.; BENDER, C.; WOEHRL, B. M.; VOGEL-BACHMAYR, K.; HUEBSCHER, U.; RAMADAN, K.; LIEBSCHER*, J.; Eur.
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