Synthesis from d-Altrose of (5R,6R,7R,8S)-5,7-Dihydroxy-8-hydroxymethylconidine and 2,4-Dideoxy-2,4-imino-d-glucitol, Azetidine Analogues of Swainsonine and 1,4-Dideoxy-1,4-imino-d-mannitol

Abstract

Ring closure of a 3,5-di-O-triflate derived from D-altrose with benzylamine allowed the formation of both monocyclic and bicyclic azetidine analogues of swainsonine.

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

“…[40] Azetidine carboxylic acid derivatives with an unprotected hydroxy group at C3, such as the amide 11, are susceptible to retro-aldol reactions under base catalysis; however, the amide 11 is stable indefinitely under neutral or acidic pH. [41] Among recent studies on the bioactivity of iminosugar azetidines, [42] potent inhibition of purine nucleoside phosphorylase [43] and specific inhibition of non-mammalian glycosidases [44,45] have been reported. Inhibition by the azetidines 10 L, 11 L, 10 D, 11 D, and 20 of the following glycosidases were studied (Table 1): [46] Neither of the enantiomeric acids 10 L and 10 D showed any inhibition (IC 50 < 50 % at 1000 mm) of any glycosidases ( Figure 4).…”

Optimization and Validation of HPLC-ELSD Method for Determination of Swainsonine in Chinese Locoweeds

“…As a unique class of N-alkyl substituents alkaloids, it's the special chemical structure that leads to particular chemical properties, spectral properties and remarkable biological properties 15 . Swainsonine can't react with alkaloid-specific chromogenic reagents such as iodoplatinate or Dragendorff's reagent and the ninhydrin colour reaction is insensitive and non-specific 16 .…”

Conformationally constrained fused bicyclic iminosugars: synthetic challenges and opportunities

“…86 The group of Tiwari also described the synthesis of compound 151b following a similar sequence, except for the azetidine ring formation which was generated via Mitsunobu reaction after hydride reduction of ester 152 to alcohol 153 (Scheme 25). 89 Condensation of benzylamine to this intermediate afforded the tricyclic azetidine 156. The modest yield observed for this reaction may be due to TBDS-induced steric crowding in the transition state.…”

“…Evaluation of the biological activity of conidine derivatives 158 and 160 on a panel of glycosidases resulted in weak inhibition of βgalactosidase (for both compounds) and α-mannosidase (for 160 only). 89 The same group also synthesized tetrahydroxyconidine 161, starting from L-arabinose and applying a similar synthetic sequence (Scheme 26). 91,92 Out of eighteen glycosidases, only rat intestinal lactase (IC 50 = 418 µM) and Rhizopus sp.…”