Design and synthesis of a bis-macrocyclic host and guests as building blocks for small molecular knots.

Elizabeth A Margolis,Rebecca J Keyes,Stephen D Lockey,Edward E Fenlon

doi:10.3762/bjoc.16.192

Elizabeth A Margolis, Rebecca J Keyes + Show 2 more

Open Access

https://doi.org/10.3762/bjoc.16.192

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Abstract

The thread–link–cut (TLC) approach has previously shown promise as a novel method to synthesize molecular knots. The modular second-generation approach to small trefoil knots described herein involves electrostatic interactions between an electron-rich bis-macrocyclic host compound and electron-deficient guests in the threading step. The bis-macrocyclic host was synthesized in eight steps and 6.6% overall yield. Ammonium and pyridinium guests were synthesized in 4–5 steps. The TLC knot-forming sequence was carried out and produced a product with the expected molecular weight, but, unfortunately, further characterization did not produce conclusive results regarding the topology of the product.

Highlights

Macrocycles have played a central role in the development of molecular recognition, self-assembled molecular devices, and molecular topology [1,2,3,4,5,6]
Exciting advances in the field of molecular topology continue with novel trefoil knots have been prepared with an all-hydrocarbon example by the Itami group [7] and the synthesis of a single enantiomer by Leigh’s group [8]
The synthesis of bis-macrocyclic host 1 began by breaking the symmetry of naphthalene-1,5-diol (4) by alkylation of one of the alcohols with 2-azidoethyl mesylate to yield azide 5 in 27% yield (Scheme 1)

Summary

Introduction

Macrocycles have played a central role in the development of molecular recognition, self-assembled molecular devices, and molecular topology [1,2,3,4,5,6]. The first-generation TLC approach for the synthesis of molecular knots involved a single knot precursor compound that had two macrocycles and two long tails [13,21]. It involves the binding of an electron-poor guest (2 or 3) in an electron-rich host (1) to promote the threading step, an alkyne–azide click cycloaddition as the linking step, and ester saponification as the cutting step [13,21] (Supporting Information File 1).

Results

Conclusion