Synthesis of 3‐Methoxyoxetane δ‐Amino Acids with D‐lyxo, D‐ribo, and D‐arabino Configurations

Starting from 1,2‐isopropylidene‐d‐xylose (1), 3‐methoxyoxetane δ‐amino acids with d‐lyxo, d‐ribo, and d‐arabino configurations were synthesized. The early introduction of an azide function at C‐5 of 1 shortened the synthetic pathway. Ring contraction of the intermediate d‐xylono‐1,4‐lactone 6 via triflation and treatment with base led to the corresponding 3‐methoxyoxetane δ‐amino ester with d‐lyxo configuration 7. The analogous procedure for d‐ribono‐1,4‐lactone 16 furnished a mixture of d‐ribo and d‐arabino esters 17 and 18. Hydrolysis of the methyl esters 7, 17, and 18 to their corresponding δ‐amino acids was successful with LiOH in THF, in contrast to that of their 3‐hydroxy analog 11.

Keywords:

• Carbohydrate amino acids
• δ‐Amino acids
• Oxetanes
• Carbohydrate scaffolds

Acknowledgments

The authors would like to thank Siegfried Stolz for recording HRMS spectra and Joseph Schneider for NOESY ¹H NMR experiments at F. Hoffmann‐La Roche, Basel. S.D. Lucas would like to thank Fundação para a Ciência e Tecnologia for a PhD grant (SFRH/BD/16592/2004).