Complex tetrahydrofurans from carbohydrate lactones: THF amino acids as building blocks for unnatural biopolymers

Abstract

The multi-gram syntheses of two epimeric six-carbon tetrahydrofurancarboxylates based upon a D-arabinofuranose template are described. An approach to 3-O-benzyl protected derivatives is also detailed. Introduction of nitrogen at C-6 of these scaffolds leads to the generation of building blocks suitable for the generation of oligomers which possess well defined secondary structures. Radical bromination facilitates introduction of nitrogen at C-2, to afford anomeric α-amino acid derivatives which are elaborated to two unnatural diastereomers of the potent herbicidal natural product hydantocidin. X-Ray crystal structures of N-methyl-2-azido-2-deoxy-α-D-arabino-hex-2-ulofuranosonamide and N-dodecyl-2-azido-2-deoxy-β-D-arabino-hex-2-ulofuranosonamide are also disclosed.