Facile Aza‐Claisen Rearrangement of Glycals: Application in the Synthesis of 1‐Deoxy‐L‐iminosugars

Abstract

Keywords:Carbohydrates / Iminosugars / Azasugars / Rearrangement / Enzymes / Inhibitors 2-C-Methylene-N-glycosyl amides have been obtained from 2-(hydroxymethyl)glycals through a facile aza-Claisen rearrangement. This rearrangement has also been utilized in the synthesis of L-allo-deoxynojirimycin, a moderate inhibitor of human lysosomal α-mannosidase (IC 50 = 64 µM), and two

Synthesis and Glycosidase Inhibition Study of 2‐C‐Hydroxymethyl‐ and 6‐C‐Hydroxymethyl‐Branched Piperidines from D‐Glucose Using Ene‐Yne Metathesis as a Key Step

“…Furthermore, compound 6d with a hydroxymethyl group at C‐2 showed much better inhibition than compound 6a , which was active against α‐mannosidase (jack beans) and α‐galactosidase (coffee beans) at concentrations of 30 and 290 μ M , respectively 9c. Likewise, similar structural features in compound 6d with the hydroxy group in the β‐orientation and the hydroxymethyl group in the α‐orientation at C‐2 led to a more effective enzyme inhibitor compared to compound 6b , in which the hydroxy group is in the α‐orientation and the hydroxymethyl group is in the β‐orientation at C‐2 11c. Compound 6b is reported to exhibit poor inhibition against α‐galactosidase (coffee beans), β‐galactosidase (bovine liver), and α‐glucosidase (rice) at concentrations of 29.00, 0.76, and 1.00 m M , respectively.…”

“…Similarly, potent α‐glucosidase inhibitors such as valiolamine ( 5a ) and voglibose ( 5b , a drug against type II diabetes) have a quaternary carbon atom that is bonded to a hydroxyl and hydroxymethyl group as their key features. In the recent past, we have introduced these typical functional groups into pyrrolidine as well as piperidine‐based imino sugars, and they turned out to be promising glycosidase inhibitors 10c,11c. Thus, in view of these literature precedents and our continued interest in the synthesis of natural and unnatural azasugar/iminosugars from carbohydrate building blocks,13 we are interested in the preparation of new molecules with combined structural features as mentioned above, that is, molecules that have a quaternary carbon atom with dihydroxyethyl and hydroxymethyl side chains.…”

Asymmetric total synthesis of L-allo-1-deoxynojirimycin

“…The O-debenzylation of urethane compound 15 was carried out using Pd(OH) 2 as the catalyst under hydrogen atmosphere followed by acid treatment to provide hydrochloride salt of L-allo-DNJ 4. 48 In principle, one can easily synthesize D-isomer of L-allo-DNJ by switching catalyst from (DHQD) 2 PHAL to (DHQ) 2 PHAL and by following same protocol.…”

Stereoselective Synthesis of C‐2‐Methylene and C‐2‐Methyl α‐ and β‐C‐Glycosides from 2‐C‐Branched Glycals: Formal Total Synthesis of (–)‐Brevisamide

“…To obtain deoxysugar‐derived 2‐vinyloxymethyl glucal 4 , 3‐deoxy‐4,6‐di‐ O ‐benzyl‐ D ‐glucal ( 1 )13 was formylated14 by using N , N ‐dimethylformamide (DMF) and POCl 3 to give 3‐deoxy‐2‐formyl‐4,6‐di‐ O ‐benzyl‐ D ‐glucal ( 2 ),15 which upon reduction by treatment with NaBH 4 in EtOH provided 3‐deoxy‐2‐hydroxymethyl‐4,6‐di‐ O ‐benzyl‐ D ‐glucal ( 3 ) 16. Vinylation of 3 by using catalytic mercuric acetate in ethyl vinyl ether provided the required 3‐deoxy‐2‐vinyloxymethyl‐4,6‐di‐ O ‐benzyl‐ D ‐glucal ( 4 ) in 60 % yield.…”