Synthesis of Eight 1‐Deoxynojirimycin Isomers from a Single Chiral Cyanohydrin

Abstract

Eight configurational 1‐deoxynojirimycin isomers have been synthesized starting from a chiral cyanohydrin as the common precursor. The cyanohydrin chiral pool building block is easily accessible in large quantities by using almond hydroxynitrile lyase as the chiral catalyst in condensing hydrogen cyanide and crotonaldehyde. Our work complements the large body of literature on the synthesis of 1‐deoxynojirimycin derivatives with the distinguishing feature that eight stereoisomers of this important class of glycosidase inhibitors can be derived from a common precursor in an efficient manner.

Sulfoxide-Directed Enantioselective Synthesis of Functionalized Tetrahydropyridines

“…One of the most versatile routes to these nitrogen-containing frameworks is the aza-Diels–Alder reaction involving either aza-dienophiles or aza-dienes . Alternatively, addition–cyclization to imines, ring expansion of furan derivatives, reduction of pyridine scaffolds, ring closing metathesis (RCM) on dialkyl substituted nitrogen substrates, or several approaches via nucleophilic attack of nitrogen onto different acceptors have been extensively employed to furnish the piperidine skeleton . Many of these strategies require the use of amino acids or substrates bearing chiral auxiliaries to give access to these valuable scaffolds.…”

Chiral disubstituted piperidinyl ureas: a class of dual diacylglycerol lipase-α and ABHD6 inhibitors

“…For the synthesis of compound 6a , we first prepared key intermediate 27 by employing a previously reported method. 15 , 24 Subsequently, removal of the Boc group using 25% (v/v) TFA in DCM generated amine 28 that was directly coupled with 4-([1,1′-biphenyl]-4-yl)-1 H -1,2,3-triazole. After silica gel chromatography, 1,4-regioisomer 29 was isolated and ensuing desilylation with HF-pyridine yielded target compound 6a ( Scheme 1 ).…”

Preparation of 1,6-di-deoxy-d-galacto and 1,6-di-deoxy-l-altro nojirimycin derivatives by aminocyclization of a 1,5-dicarbonyl derivative

“…Some works reported the syntheses of 1-deoxynojirimycin and its isomers employing as starting materials substrates from the chiral pool such as carbohydrates [23][24][25] or amino acids [26,27]. Other strategies started instead from different open chain precursors and were based on chemoenzymatic [28,29] or asymmetric reactions such as dihydroxylation [30], aldol reaction coupled with a reductive amination [31] or aminohydroxylation [32] transformations.…”