Azide- and Alkyne-Functionalised α- and β³-Amino Acids

Abstract

The synthesis and full characterisation of bifunctional β³-amino acids that have side chains functionalised with terminal azides (S)-4 and (R)-4 or acetylenes 5 and 6 is reported for the first time. The building blocks incorporate a turn-inducing β³-segment and a side chain that can be functionalised further, for example, through copper-catalysed Huisgen cycloaddition. Moreover, the corresponding α-amino acids 1 and 3 have been synthesised and characterised. All amino acid building blocks were of high optical purity as demonstrated by derivatisation and subsequent NMR analysis.

Key words

alkynes - azides - amino acids - diazotransfer - Arndt–­Eistert homologation - peptidomimetics

• References and Notes

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• 32 Many azido-functionalised α-amino acids are commercially available. However, to the best of our knowledge no optically active azido-functionalised β³-amino acids are available.

Both enantiomers of amino acid 5 are commercially available from a number of vendors and according to Chemical Abstract (CAS) have been reported in two Chinese papers:
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• 34 Attempting the reaction on the methyl ester derivative of 15 under the same reaction conditions led to the formation of several side products, reduced yields, and significant racemisation.