Oxetane δ‐Amino Acids: Chemoenzymatic Synthesis of 2,4‐Anhydro‐5‐N‐(t‐butoxycarbonyl)amino‐D‐lyxonic Acid

Abstract

Starting from 1,2‐O‐isopropylidene‐D‐xylose, methyl 2,4‐anhydro‐3,5‐di‐O‐benzyl‐D‐lyxonate (4) was synthesized. Debenzylation and transformation of the primary hydroxyl group yielded methyl 2,4‐anhydro‐5‐N‐(t‐butoxycarbonyl)amino‐D‐lyxonate (9). While transesterification of 4 under basic reaction conditions was straightforward, an analogous reaction with 9 was not successful. After screening of several lipases, the enzymatic transesterification of 9 was achieved with lipase L2 from Candida antarctica to furnish the title compound 2,4‐anhydro‐5‐N‐(t‐butoxycarbonyl)amino‐D‐lyxonic acid in excellent yield. The stereochemistry at the oxetane ring was proven by an x‐ray structure of the intermediate methyl 2,4‐anhydro‐5‐azido‐D‐lyxonate.

Keywords:

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

Acknowledgements

We wish to thank Amélie Mourton and Solène Dussauge for preliminary experiments.