Abstract
Straightforward syntheses of cyclopropyl analogues of β-homoornithine and β-homoglutamic
acid are reported. The key step is the titanium-mediated cyclopropanation of 3-benzyloxypropionic
acid N,N-dibenzylamide (6), affording N,N-dibenzyl-N-[1-(2-benzyloxyethyl)-2-ethenylcyclopropyl]amine (7) in 56% yield as a 2.5:1 mixture of E- and Z-diastereomers. Further transformations of 7 in 9 and 6 simple steps, respectively, furnished 3,6-bis(N-tert-butoxycarbonylamino)-3,4-methanohexanoic acid (13) and 3-(N-tert-butoxycarbonylamino)-3,4-methanohexane-1,6-diacid dimethylester (16) as interesting protected β-(aminocyclopropyl)carboxylic acid building blocks for
potentially active small peptide analogues. The structure of the crystalline intermediate
tert-butyl (E)-N-{2-[2-(N-tert-butoxycarbonylamino)ethyl-1-(2-hydroxyethyl)]cyclopropyl}carbamate (12) was proved by X-ray diffraction.
Key words
amino acids - low valent titanium - medicinal chemistry - cyclopropanes - structure
elucidation
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