Spiro[2.3]hexane‐ and Spiro[3.3]heptane‐derived α‐Amino Acids: Synthesis and Isoelectric Point Evaluation

Abstract

An efficient synthesis of spiro[2.3]hexane‐ and spiro[3.3]heptane‐derived α‐amino acids is reported. The used methods are divided on two different approaches. First of them involves modification of commercially available spirocyclic diesters via monohydrolysis, Curtius rearrangement and functional groups deprotection sequence. Alternative approach was based on Bucherer ‐ Bergs hydantoine synthesis with its subsequent cleavage to the target amino acid fragment. The proposed synthetic schemes offer the desired product in 31–52 % overall yield on up to 22.5 g scale. Acid‐base titration of the obtained spirocyclic amino acids revealed lowered pI values compared to the parent 1‐amino‐cyclohexane‐ and ‐cycloheptanecarboxylic acids.