Synthesis of skeletally diverse alkaloid-like molecules: exploitation of metathesis substrates assembled from triplets of building blocks

Sushil K Maurya,Stuart Warriner,Mark Dow,Adam Nelson

doi:10.3762/bjoc.9.88

Abstract

A range of metathesis substrates was assembled from triplets of unsaturated building blocks. The approach involved the iterative attachment of a propagating and a terminating building block to a fluorous-tagged initiating building block. Metathesis cascade chemistry was used to “reprogram” the molecular scaffolds. Remarkably, in one case, a cyclopropanation reaction competed with the expected metathesis cascade process. Finally, it was demonstrated that the metathesis products could be derivatised to yield the final products. At each stage, purification was facilitated by the presence of a fluorous-tagged protecting group.

Highlights

Our collective understanding of the biological relevance of chemical space has been shaped, in large part, by the historic exploration of chemical space by chemical synthesis [1]
We have previously developed a robust approach for the synthesis of skeletally diverse small molecules (Scheme 1) [14]
It was demonstrated that metathesis substrates could be assembled efficiently from triplets of building blocks

Summary

Introduction

Our collective understanding of the biological relevance of chemical space has been shaped, in large part, by the historic exploration of chemical space by chemical synthesis (and biosynthesis) [1]. The approach relied on the synthesis of metathesis substrates by Beilstein J. Scheme 1: Illustrative examples of a synthetic approach to natural-product-like molecules with over eighty molecular scaffolds. Metathesis cascade reactions were used to “reprogram” the molecular scaffolds, concomitantly releasing the products from the linker (e.g., → 4 or 5) [14,15,16,17].

Results

Conclusion