Dynamic combinatorial chemistry with hydrazones: cholate-based building blocks and libraries.
We describe an efficient and general strategy for the synthesis of dimethyl acetal functionalised steroidal hydrazides based on the cholic acid skeleton with the aim of using these compounds as building blocks for dynamic combinatorial chemistry. Deprotection of the acetal protected building blocks with TFA leads to formation of libraries containing macrocyclic N-acyl hydrazone oligomers. The isolation of several of these, and their characterisation using NMR is described. The effects on the equilibrium library distribution by varying the substituents at C-7 and C-12, extending the side-chain with glycine, and inverting the configuration at C-3 are discussed. Finally, we report the exchange properties of these macrocycles and demonstrate new examples of proof-reading and self-sorting in dynamic combinatorial libraries.
Simpson
Mark G
MG
University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, United Kingdom.
Pittelkow
Michael
M
Watson
Stephen P
SP
Sanders
Jeremy K M
JK
D020355:Cholates / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques / Q000191:economics / Q000379:methods*; D003500:Cyclization; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure
D020355:Cholates; D006835:Hydrazones