Azetidine Iminosugars from the Cyclization of 3,5-Di-O-triflates of α-Furanosides and of 2,4-Di-O-triflates of β-Pyranosides Derived from Glucose

Abstract

Primary amines with either 3,5-di-O-ditriflates of α-furanosides or 2,4-di-O-triflates of β-pyranosides form bicyclic azetidines in high yield.

3‐Hydroxyazetidine Carboxylic Acids: Non‐Proteinogenic Amino Acids for Medicinal Chemists

“…Under similar conditions the corresponding a-pyranoside 16 a did not form any bicyclic product; only b-anomers of such pyranosides cyclized to azetidines in good yield. [36] Hydrolysis of 17 by aqueous hydrochloric acid in dioxane gave the lactols 18 L. Reduction of 18 L by sodium borohydride, followed by purification via an acetylation-deacetylation sequence to remove the borate complexes, gave the dibenzyl diol 19 (74 %). Removal of the benzyl group by hydrogenolysis in aqueous dioxane in the presence of palladium on carbon and hydrochloric acid gave the meso-iminoribitol azetidine 20.…”

“…Hydrolysis of 21 L by hydrochloric acid in aqueous dioxane gave the acid 22 L (81 %) from which the benzyl groups were removed by hydrogenolysis to afford the unprotected 3-hydroxyazetidine carboxylic acid 10 L. Treatment of the methyl ester 21 L with methylamine in methanol in the presence of anhydrous calcium chloride [38] formed the amide 23 L (70 %) which, upon hydrogenolysis, formed the unprotected amide 11 L. For the enantiomeric acid 10 D and amide 11 D, the azetidine 25 was formed from the glucose-derived ditriflate 24 as previously described (Scheme 2). [36] Oxidation of 25 with sodium periodate in aqueous acetone gave the lactols 18 D which, upon further oxidation by iodine in methanol, formed the methyl ester 21 D (77 %). Subsequent transformations on 21 D, identical to those performed on 21 L, allowed access to the 3-hydroxy-dazetidine carboxylic acid 10 D and the corresponding amide 11 D. The structure of the dibenzyl acid 22 D was firmly established by X-ray crystallographic analysis ( Figure 3).…”

“…The residue was dissolved in anhydrous MeOH (2 mL); NaOMe (4 mg, 0.07 mmol) was added, and the reaction mixture was stirred at RT for 20 h. TLC analysis (EtOAc) indicated consumption of starting material (R f = 0.95) and formation of a major product (R f = 0.54) along with an additional species (R f = 0.87), which was tentatively identified as the monoacetate (by MS), and an additional quantity of NaOMe (4 mg, 0.07 mmol) was added to the reaction mixture. After a total reaction time of 45 [36] NaIO 4 (117 mg, 0.55 mmol) was added to a solution of the triol 25 (159 mg, 0.46 mmol) in aqueous acetone (H 2 O/acetone, 2:1, 6 mL), and the reaction mixture was stirred at RT for 1 h. TLC analysis (EtOAc) indicated consumption of the starting material (R f = 0.30) and formation of a single new compound (R f = 0.67). EtOH (24 mL) was added, the reaction was stirred for 45 min, and the resultant precipitate was removed by filtration (GF/A glass microfiber).…”

Larger laboratory scale synthesis of 5-methyluridine and formal synthesis of its L-enantiomer

“…A small amount of this material was purified by chromatography using CH2Cl2 -MeOH 9:1 to get the crystalline material, mp 130-134 °C (EtOAc -EtOH); lit. 32 mp. 131-133 °C (Et2O -MeOH) The bulk of the crude product was dissolved in 96% EtOH (250 mL) and treated with a suspension of NaIO4 (30 g, 140 mmol), in H2O (100 mL) with magnetic stirring.…”

“…The other oxidants include DMSO-P2O5, 27 pyridinium dichromate-Ac2O, 28 pyridinium chlorochromate, 29 and RuCl3-NaIO4, 30 (RuO2-NaIO4 31 was reported to also form Baeyer-Villiger overoxidation products) and finally Dess-Martin periodinane. 32 DMSO-Ac2O is not a very active system and its application may result in incomplete conversion of 7 into 8, and consequently, the next reduction step may furnish a mixture of the allose 9 and unreacted glucose 7, which are difficult to separate. In fact, unreacted 7 was reported to be present even after 24 h of reaction time.…”