Synthesis of Trehazolin from d-Glucose

Abstract
Trehazolin (2) is a specific inhibitor of trehalase, an enzyme that cleaves the reserve carbohydrates of many insects. We describe a short and efficient synthesis of trehazolin (2) and trehazolamine (5) that mimics its hypothetical biosynthesis. Starting molecule for the synthesis of trehazolamine (5) is glucose from which three chiral centers are conserved during the reaction sequence. The remaining two chiral centers of trehazolamine (5) are formed stereoselectively in a reductive cyclization of ketooxime ether 16 and the reduction of oxime ether 18. The overall yield of trehazolamine (5) is 22% over 8 steps from 15. The synthesis of trehazolin (2) from trehazolamine (5) follows a known procedure and is achieved in 63% over 3 steps.