Stereoselective Synthesis of Bishomo-inositols as Glycosidase Inhibitors

Abstract

For the synthesis of various bishomo-inositol derivatives, 1,3,3a,7a-tetrahydro-2-benzofuran was used as the key compound. For further functionalization of the diene unit, the diene was subjected to photooxygenation, epoxidation, and cis-hydroxylation reactions. The endoperoxide linkage was cleaved by thiourea. The remaining double bond was subjected to epoxidation and cis-hydroxylation reactions. The epoxide rings and tetrahydrofuran rings formed were opened by acid-catalyzed reaction with sulfamic acid. The combination of these reactions resulted in the formation of various new inositol derivatives such as bishomo-chiro-inositol, bishomo-myo-inositol, and two isomeric bishomo-allo-inositols.

Synthesis and α‐Glucosidase and α‐Amylase Inhibitory Activity Evaluation of Azido‐ and Aminocyclitols

“…Removal of the chlorobenzoate group in 26a followed by acetylation resulted in the formation of symmetrical diacetate 27 . The spectroscopic data of 27 exactly matched those of the product obtained by photooxygenation of diene 6 followed by cleavage of the peroxide linkage and then acetylation 7b. The exclusive formation of 26a as a single isomer can again be explained by the cis ‐directing effect of the neighbouring hydroxy group, as discussed above.…”

“…Diene 6 was synthesized in five steps, starting with the addition of maleic anhydride to in‐situ‐generated butadiene 7b,9. Reduction of the anhydride8 functionality followed by addition of bromine and subsequent elimination of HBr gave diene 6 , which was used for the synthesis of various aminocyclitols.…”

Glycosidase inhibitors: versatile tools in glycobiology

“…Concerning polyhydroxylated quinolizidines, Pandey et al described 70 a divergent route starting from D-ribose (Scheme 16 displays the retrosynthetic analysis) to get a small library of quinolizidine alkaloids (111)(112)(113)(114)(115)(116)(117)(118)(119)(120)(121)(122)(123). Among them, two compounds had remarkable inhibitory properties: 112, against a-galactosidase from coffee beans (K i= 83.9 mM), and 123, against a-glucosidase from yeast (K i= 28 mM).…”

“…17). [118][119][120] Conduramine F-1 epoxides 216-218 (Scheme 27) 121 were synthesized starting from (AE)-7-oxanorbornenone 214, using cyclohexene derivative 215 as the key intermediate, which was subjected to an epoxidation reaction. All compounds behaved as poor inhibitors against b-D-galactosidase (bovine liver) and amyloglucosidase (Aspergillus niger); however compounds 216 and 217, bearing trans epoxy and amino moieties, exhibited potent non-competitive inhibition of b-D-xylosidase (Aspergillus niger; K i= 48 mM and 2.2 mM, respectively).…”

Synthesis of Anti–-anti (anti–-syn)-3,4:8,9-Tetraacetoxy-11-Oxa-Tricyclo [4.4.1.01,6]Undecanes

“…8 Polyhydroxylated cycloalkanes such as cyclitols and carba-sugars have received an increased amount of attention due to their wide range of biological activities. [9][10][11][12] The synthesis of polycyclitols like 2 as new structural variants has been achieved. 13 Polyhydroxylated cycloalkanes including epoxy ring are a concise intermediate for the synthesis of inositols.…”