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 starting from D-glucose. The key transformation in this approach is a high-yielding two-step, one-pot sequence consisting of a Swern oxidation of a 1,5-diol followed by a reductive carbocyclization of the resultant 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-glucose (5). An even shorter synthesis of 30, a diastereoisomeric analogue of 3, is also described starting from 5. The key transformation in this second route is a highly stereoselective ketone oxime ether reductive carbocyclization promoted also by samarium diiodide. The overall yield of 30 is 57% over four steps from 5.
Storch De Gracia
Isabel
I
Instituto de Química Orgánica General, CSIC, Juan de la Cierva, 3, E-28006 Madrid, Spain.
Dietrich
Hansjörg
H
Bobo
Sofía
S
Chiara
Jose Luis
JL