Synthesis of trehazolin analogues containing modified sugar moieties

Abstract

In order to elucidate the biological roles of the sugar moiety of the trehalase inhibitor trehazolin 1, the sugar portion was first replaced with hydrophobic aromatic functions, providing the N-phenyl 3 and N-benzyl derivatives 4 of trehazolin 1. Then the six analogues with the sugar moiety being replaced with D-mannopyranose 5, 3-deoxy-ribo-hexopyranose 6, D-galactopyranose 7, 6-deoxy-D-glucopyranose 8, 5a-carba-α-D-glucopyranose 9 and 5a-carba-α-D-xylo-hex-5(5a)-enopyranose residues 10 were synthesized.

In the hope of improving the fungicidal activity of trehazolin 1, we prepared two disaccharide analogues, 11 and 12, containing maltose and cellobiose residues. A remarkable decrease in potency was observed in the analogues 5–8 and 10, but not for 5a′-carbatrehazolin 9, suggesting an essential role for the D-gluco configuration of the hexopyranose portion. The β-D-glucosyl analogue 12 showed an increase in antifungal activity against Rhizoctonia solani, as compared with that of trehazolin 1. The analogues 3 and 4 were not trehalase inhibitors, but rather were moderate α-glucosidase inhibitors.