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.

Solid-Phase Tandem Radical Addition-Cyclization Reaction: Triethylborane-Induced Reaction of Oxime Ethers Anchored to Polymer Support

“…16,17) Free radical-mediated cyclization has been developed as a powerful method for preparing various types of cyclic compounds via carbon-carbon bond-forming processes. [18][19][20][21][22][23][24][25][26][27][28][29] Our laboratory is interested in developing the effective and convenient methods for the synthesis of highly functionalized cyclic compounds. For this purpose, we have studied the radical reaction using oxime ether group as a radical acceptor.…”

Stannyl Radical Addition-Cyclization of Oxime Ethers Connected with Olefins

“…6,7) Our laboratory is interested in developing the effective and convenient methods for the synthesis of highly functionalized cyclic compounds. [8][9][10][11][12][13][14][15][16][17][18][19][20][21] Particularly, strategies involving the radical addition-cyclization reactions offer the advantage of the formation of multiple carbon-carbon and carbon-heteroatom bonds in a single operation. We recently reported the carbon tandem radical addition-cyclization of oxime ethers connected with the a,b-unsaturated carbonyl group.…”

Stereoselective Synthesis of an Aminocyclopentitol Analog of α-l-Fucose via an Allylic Bromohydrin

“…For the case where Z = OH (Scheme 1), the samarium-promoted reductive cyclization of protected 5-keto glucose oximes on the way to trehazolins establishes such an anti-relationship, 7 as does a stereoselective dihydroxylation of a peracetylated 4-amino-5-methylene-cyclopentane-1,2,3-triol. 8 For the case where Z = H (Scheme 1), a base-catalyzed epimerization at C(5) via the aldehyde at C(6) was used after an intramolecular oxime-olefin cycloaddition to establish an anti relationship between the amino group and the hydroxymethyl group, leading to an inhibitor of a-mannosidase.…”