Novel Polyhydroxylated Cyclic Nitrones and N-Hydroxypyrrolidines through BCl₃-Mediated Deprotection

Abstract

A general method to prepare a new class of carbohydrate-derived, enantiomerically pure polyhydroxypyrroline N-oxides from their alkoxy (protected) derivatives is presented. Boron trichloride is shown to cleave efficiently benzyl ethers and ketals without affecting the imine N-oxide functionality of nitrones. The same reagent (BCl3) also allowed the efficient synthesis of a polyhydroxylated N-hydroxypyrrolidine, giving access to a novel class of N-hydroxyiminosugars.

Human Acid β‐Glucosidase Inhibition by Carbohydrate Derived Iminosugars: Towards New Pharmacological Chaperones for Gaucher Disease

“…[14] This compound was the key buildingb lock for the preparation of the glycosidase inhibitorD AB-1 (5), [15,16] 6-deoxy-DMDP (6) [16][17][18] and the deprotected nitrone 7 obtained by BCl 3 -mediated O-benzyl deprotection as reported by Py and co-workers (Scheme 2A). [19] Analogously, d-xylose-derived 8,o btained in a few steps from d-xylose, [14d,e] allowed the straightforward synthesis of 1,4-dideoxy-1,4-imino-d-xylitol (9;S cheme 2B), [20,21] an atural product recently found in marine sponges. [22][23][24] The same procedure was applied to 10,r eadily derived from d-ribose, [14e, 25] therebya ffording quantitatively1 ,4-dideoxy-1,4-imino-d-ribitol (11,S cheme2C), [26] an atural compound previously reported to inhibit a-glucosidase and b-mannosidase, [17b, 18, 23] by catalytic hydrogenation.…”

Glucocerebrosidase Enhancers for Selected Gaucher Disease Genotypes by Modification of α‐1‐C‐Substituted Imino‐D‐xylitols (DIXs) by Click Chemistry

“…Conversion of alkene 3 into the corresponding alkyne 4 was performed in two steps (68 % combined yield) by means of Lemieux-Johnson oxidative cleavage and reaction of the intermediate aldehyde with an excess of the Bestmann-Ohira reagent. [29] At this stage, the chemoselective deprotection of the O-benzyl groups in 4 proved difficult, and our first attempts using boron trichloride [30] or TMSI [31,32] led to a complex mixture of products. In this context, the deprotection of O-benzyl groups using boron trichloride in the presence of an alkyne functionality were described as troublesome, [23] due to the reactivity of the CÀC triple bond.…”

Glycosidase Inhibition with Fullerene Iminosugar Balls: A Dramatic Multivalent Effect

“…Oxidation of the hydroxy group at C5 followed by intramolecular Selective cleavage of the benzyl protecting groups of 4 without interfering with the azide moiety was performed successfully by treatment with an excess of BCl 3 in CH 2 Cl 2 at low temperatures (À60 -08C). [20] Reaction of the resulting compound 5 [21] with 1-pentyne in the presence of CuSO 4 ·5 H 2 O and sodium ascorbate gave the derivative 6, which was used as the monovalent model compound in the inhibition assay. The synthesis of fullerene iminosugar ball 8 is shown in Scheme 2.…”