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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Dynamic combinatorial chemistry with hydrazones: libraries incorporating heterocyclic and steroidal motifs
Mark G Simpson1, Michael Pittelkow, Stephen P Watson
1University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, United Kingdom.
Abstract:
We expand the possibilities in hydrazone based dynamic combinatorial chemistry with a series of new building blocks incorporating heterocyclic motifs. The synthetic procedure allows efficient access to building blocks with the general structure (MeO)(2)CH-Heterocycle-C(O)NHNH(2), originating from heterocycles with an amine and an ester functionality. The equilibrium distribution of macrocyclic N-acyl hydrazones formed upon deprotection of the building blocks with TFA in organic solvents is reported. The mixing behaviour of these heterocycle-based building blocks with our cholate-based building blocks is described, particularly the observation of kinetic intermediates that disappear following 'proof-reading'.
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