Asymmetric synthesis of 1-deoxyazasugars from chiral aziridines

Abstract

A general and facile synthesis of enantiopure 1-deoxyazasugars was achieved from stereoselective dihydroxylation of a common synthetic intermediate, piperidine ring fused oxazolidin-2-one, originating from a commercially available starting substrate, chiral aziridine-2-carboxylate, in high yields.

Application of Regio‐ and Stereoselective Functional Group Transformations of Chiral Aziridine‐2‐carboxylates

“…Asymmetric synthesis of a set of the six different stereoisomers of (L)‐deoxynojirimycins including L ‐1‐deoxyidonojirimycin, ( L ‐ido‐DNJ), L ‐1‐deoxygalactonojirimycin ( L ‐galacto‐DNJ), L ‐1‐deoxygulonojirimycin ( L ‐gulo‐DNJ), L ‐1‐deoxynojirimycin ( L ‐DJN), L ‐1‐deoxyaltronojirimycin ( L ‐altro‐DNJ) and L ‐1‐deoxymannojirimycin ( L ‐man‐DNJ) was achieved from (2 S )‐aziridine‐2‐carboxylate 1′ (Scheme ) 36. The common stereocenters of all six isomers at the C2 position share the 2 S configuration of the starting (2 S )‐aziridine‐2‐carboxylate.…”

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

“…To synthesize stereoisomeric ʟ-deoxynojirimycins having the R configuration at C3 [(2 S ,3 R ,4 R ,5 S )- 200 (ʟ-1-deoxyidonojirimycin), (2 S ,3 R ,4 R ,5 R )- 200 (ʟ-1-deoxygulonojirimycin) and (2 S ,3 R ,4 S ,5 R )- 200 (ʟ-1-deoxygalactonojirimycin)] the aziridine alcohol (2 S ,1' S ,1'' R )- 202 prepared by reduction of the ketone (2 S ,1' R )- 201 with ʟ-Selectride ® was transformed into the bicyclic intermediate 210 , the epimer of 205 , as already shown (Scheme 53) [88]. Furthermore, syntheses of six stereoisomers of ᴅ-1-deoxynojirimycins were accomplished starting from the ester (2 R ,1' R )- 5b and proceeding as already shown in Scheme 53 [88].…”

“…From several syntheses of this compound the general approach which employs the aziridine ester (2 R ,1' R )- 5b as a starting material allows to also obtain its 5'-epimer and norfuranomycin (2 S ,2' R )- 133 [87]. To construct the 2,5-dihydrofurane ring the aziridine alcohol (2 R ,1' R ,1'' R )- 134 (Scheme 35) [88] was converted to the allyl ether (2 R ,1' R ,1'' R )- 135 which in the presence of Grubbs 1st generation catalyst produced (2 R ,1' R ,1'' R )- 136 . Transformation of the aziridine portion of 136 into an amino acid fragment of norfuranomycin (2 S ,2' R )- 133 was accomplished starting from the hydrolytic opening of the aziridine ring and was followed by protection of the amino alcohol and Birch debenzylation to give 137 .…”

“…1-Deoxynojirimycin was discovered in several natural species and later found as a potent inhibitor of glycosidases [110]. ʟ-1-Deoxynojirimycin ((2 S ,3 S ,4 S ,5 R )- 200 ) and five of its stereoisomers were synthesized in a unique approach using (2 S ,1' R )- 5b as a starting material [88]. When the aziridine ketone (2 S ,1' R )- 201 was treated with a NaBH 4 /ZnCl 2 mixture the aziridine alcohol (2 S ,1' R ,1'' R )- 202 was stereoselectively formed in a chelation-controlled reduction establishing the absolute configurations at C2 and C3 in three final products (2 S ,3 S ,4 S ,5 R )- 200 , (2 S ,3 S ,4 S ,5 S )- 200 , (2 S ,3 S ,4 R ,5 S )- 200 .…”

Stereoselective synthesis of 2-acetamido-1,2-dideoxynojirimycin (DNJNAc) and ureido-DNJNAc derivatives as new hexosaminidase inhibitors

“…The protected compounds were prepared by introducing the amino function by nucleophilic ring opening of an epoxide or a cyclic sulfate obtained from the key intermediate 11, which is readily accessible by Sharpless asymmetric epoxidation of 2,4-pentadien-1-ol. 47 This intermediate has been widely used for the synthesis of various iminosugars 17,[48][49][50] including our recent synthesis of DAJNAc (9). 42 Scheme 1.…”