Tetrahydroisoquinolines library

Griffith MC, Dooley CT, Houghten RA, Kiely JS, Solid-phase synthesis, characterization, and screening of a 43,000-compound tetrahydroisoquinoline combinatorial library, in Molecular Diversity and Combinatorial Chemistry (Eds Chaiken IW, Janda KD), pp. 50-57, 1996, American Chemical Society, Washington. 

This linker was employed in the synthesis of a library of N-alkylated 5- and 6-alkyloxy-l,2,3,4-tetrahydroisoquinolines 77 involving the following steps Michael addition, acid-catalyzed removal of a THP group, Mitsunobu etherification, quaternization of the nitrogen, and Huenig s base-catalyzed elimination [86] (Scheme 36). 

Isoquinoline derivatives are an important family of natural products. They have diverse biological activities and are used, for example, as bronchodi-lators, skeletal muscle relaxants, and antiseptics. The solid-phase synthesis of a 43,000-compound tetrahydroisoquinoline 2 combinatorial library has been reported by Griffith et al. [32]. The library was synthesized by a three-step procedure. An imine was formed by reacting a substituted benzaldehyde with a methylbenzhydrylamine (MB HA) resin-bound amino acid. Imine formation was driven to completion using trimethylorthoformate as a dehydrating reagent. Treatment of the imine with homophthalic anhydride provided the desired tetrahydroisoquinoline (Fig. 3a). 

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