A HIGHLY EFFICIENT PINACOL COUPLING APPROACH TO TREHAZOLAMINE STARTING FROM D-GLUCOSE

A short and very efficient synthesis of trehazolamine (3), the aglycon of the potent trehalase inhibitor trehazolin (2), has been achieved s tarting from D-glucose. The key transformation in this approach is a h igh-yielding two-step, one-pot sequence consisting of a Swern oxidatio n of a 1,5-diol followed by a reductive carbocyclization of the result ant 1,5-dicarbonyl compound promoted by samarium diiodide. The overall yield of 3 is 39% over nine steps from 2,3,4,6-tetra-O-benzyl-D-gluco se (5). An even shorter synthesis of 30, a diastereoisomeric analogue of 3, is also described starting from 5. The key transformation in thi s second route is a highly stereoselective ketone oxime ether reductiv e carbocyclization promoted also by samarium diiodide. The overall yie ld of 30 is 57% over four steps from 5.