From Solution-Phase Studies to Solid-Phase Synthesis: A New Indole Based Scaffold for Combinatorial Chemistry

Authors

  • David Orain
  • Guido Koch
  • Rudolf Giger

DOI:

https://doi.org/10.2533/000942903777679343

Keywords:

Combinatorial chemistry, Dakin-west, Natural products, Pictet-spengler, Tryptophan

Abstract

The core structure of a natural product was selected as scaffold for combinatorial library synthesis. The key step for the construction of the 3,9-diazabicyclo[3.3.1]non-6-ene core is a novel Dakin-West/Pictet-Spengler reaction sequence. Route selection for library synthesis was determined by solution-phase experiments. The solid-phase synthesis was developed based on the synthesis worked out in solution. A number of resins and linkers were studied to obtain the best loading and cleavage conditions. Potential target scaffolds using tryptophan, histidine and phenylalanine as building blocks were investigated. These efforts led to the development of a synthesis protocol for a tetracyclic scaffold incorporating tryptophan, useful for the preparation of a combinatorial library.

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Published

2003-05-01

Issue

Section

Scientific Articles