Multifunctionality of the N-Trichloroacetyl Group Developed in the Synthesis of Tetrodotoxin, a Puffer Fish Toxin

Abstract

This account describes a serendipitous discovery and the development of unique reactions associated with trichloroacetamide during synthetic studies of tetrodotoxin in our laboratory. The reactions include site-selective hydroxylation using the neighboring-group participation of trichloroacetamide, guanidinylation from a trichloroacetamide, protecting-group transformation, and removal of the N-trichloroacetyl group. These studies indicate the importance of the total synthesis of densely functionalized natural products as a field for the development of new reactions.

1 Introduction

2 Improvement of the Conditions for the Overman Rearrangement to Introduce Trichloroacetamide

3 Site-Selective Hydroxylation Using the Neighboring-Group Participation of Trichloroacetamide

4 Guanidine Synthesis

5 Protecting-Group Transformation of the N-Trichloroacetyl Group

6 New Deprotection Conditions for the Removal of the N-Trichloroacetyl Group

7 Conclusion

Key words

protecting groups - tetrodotoxin - trichloroacetamide - neighboring-group effects - protecting-group transformations

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