A C-amide-substituted O-silylated oxime, (E)-(tert-butyldimethylsiloxyimino)acetic acid N,N-dimethylamide (8b), on treatment with 2.2 equiv of BF3·OEt2, in situ generated boracyclic nitrone-type intermediate BF3·14, which underwent cycloaddition with alkenes to give 3,5-cis-isoxazolidines as the major products. The mechanism was strongly supported by isolation of the reaction intermediate 14 that was characterized by X-ray diffraction and its further reaction. This cycloaddition was successfully applied to the synthesis of syn-HPA-12 known as an inhibitor of CERT that mediates the transport of ceramide.

Twenty-one natural and unnatural phenolic compounds containing a carbohydrate moiety were synthesized and their structure–activity relationship (SAR) was evaluated for α-glucosidase inhibition and antioxidative activity. Varying the position of the galloyl unit on the 1,5-anhydro-d-glucitol (1,5-AG) core resulted in changes in the α-glucosidase inhibitory activity and notably, particularly strong activity was demonstrated when the galloyl unit was present at the C-2 position. Furthermore, increasing the number of the galloyl units significantly affected the α-glucosidase inhibition, and 2,3,4,6-tetra-galloyl-1,5-AG (54) and 2,3,4,6-tetra-galloyl-d-glucopyranose (61) exhibited excellent activities, which were more than 13-fold higher than the α-glucosidase inhibitory activity of acertannin (37). Moreover, a comparative structure-activity study suggested that a hemiacetal hydroxyl functionality in the carbohydrate core and a biaryl bond of the 4,6-O-hexahydroxydiphenoyl (HHDP) group, which are components of ellagitannins including tellimagrandin I, are not necessary for the α-glucosidase inhibitory activity. Lastly, the antioxidant activity increased proportionally with the number of galloyl units.

BF 3-Mediated cis-Selective Cycloaddition of O-Silyloxime with Alkenes. -O-Silyloxime (I) reacts with alkenes (II) and Boc 2O to the Boc-protected isoxazolidin-3-carboxamides (IV) and (V) favouring the cis-isomer (IV). Cyclopentene gives mainly the perhydrocyclopent[d]isoxazolidine-3-carboxamide (VII). Cis-compound (IVd) can be easily transformed into the pharmacologically prospective racemic derivative syn-HPA-12 (IX), a known CERT inhibitor. -(MORITA, N.; KONO, R.; FUKUI, K.; MIYAZAWA, A.; MASU, H.; AZUMAYA, I.; BAN, S.; HASHIMOTO, Y.; OKAMOTO, I.; TAMURA*, O.; J. Org. Chem. 80 (2015) 9, 4797-4802, http://dx.doi.org/10.1021/acs.joc.5b00426 ; Showa Pharm. Univ., Machida, Tokyo 194, Japan; Eng.) -M. Tismer 39-124

No abstract