Abstract

During efforts to prepare the known compound , a new tetracyclic compound, called VG1, was prepared in six steps. This compound was found to have good activity as an inhibitor of nonsense-mediated mRNA decay.

Highlights

  • During efforts to prepare the known compound NMDI1, a new tetracyclic compound, called VG1, was prepared in six steps

  • premature termination codon (PTC)-associated diseases include cases of Duchenne muscular dystrophy, cystic fibrosis, β-thalassaemia, retinitis pigmentosa, von Willebrand disease, Robinow syndrome, haemophilia, spinal muscular atrophy and Rett syndrome. mRNAs containing PTCs are detected and degraded by a process known as nonsense-mediated mRNA decay (NMD),[2,3,4] which reduces the expression of the corresponding gene to a low level

  • Keeling and co-workers have recently reported a synthesis of NMDI1 by a modified route in which the final 7 steps were identical to those used by Bisagni and co-workers; they report no experimental details.[8]

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Summary

Introduction

During efforts to prepare the known compound NMDI1, a new tetracyclic compound, called VG1, was prepared in six steps. In 2007, Lejeune and coworkers[5] found that a tetracyclic compound called NMDI1 (Fig. 1) was able to inhibit both nucleus-associated and cytoplasmic NMD.

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