New series of N-aryl- and N-heteroaryl-d-glucuronamides as potential anticancer agents: synthesis and spectroscopic analysis. Issue 7 (1st May 2016)

• Record Type: Journal Article
• Authors: Hricovíniová, Zuzana; Hricovíni, Michal; Brezová, Vlasta; Magdolen, Peter
• Is Part Of: Tetrahedron, asymmetry. Volume 27:Issue 7/8(2016)
• Page Start: 361
• Page End: 368
• Publication Date: 2016-05-01
• Subjects: Asymmetry (Chemistry) -- Periodicals; 547.005
• DOI: 10.1016/j.tetasy.2016.02.015
• Languages: English
• ISSNs: 0957-4166

Abstract

Graphical abstract: Abstract: A series of structurally diversed -glucuronic acid derivatives, comprising various aromatic scaffolds, was prepared and characterized with the aim of developing new prodrug candidates. The presented ultrasound-assisted protocol provides a convenient way for the synthesis of N -aryl- and N -heteroaryl-substitutedd -glucuronamides with improved bioavailability. New conjugates containing benzene, naphthalene, indole, quinoxaline, and benzothiazole moieties were prepared in high yields (41–85%). Their structures were elucidated by various spectroscopic methods, including NMR, and their potential in the photoactivation of molecular oxygen was monitored by EPR spectroscopy. The application of the presented approach for the synthesis of potentially biologically active compounds makes the method attractive because of their potential use in biomedical and pharmaceutical chemistry. Abstract : 1, 2, 3, 4-Tetra- O -acetyl-β-d -glucuronic acid anhydride: C16 H20 O12 Ee = 100% [ α ]D 20 = +5.4 ( c 1, CHCl3 ) Source of chirality: synthesis d -Glucuronic acid as starting material Abstract : N -(4-Nitrophenyl)-1, 2, 3, 4-tetra- O -acetyl-β-d -glucuronamide: C20 H22 O12 N2 Ee = 100% [ α ]D 20 = −1.3 ( c 1, CHCl3 ) Source of chirality: synthesis 1, 2, 3, 4-Tetra- O -acetyl-β-d -glucuronic acid anhydride as starting material Abstract : N -(4-Chloro-3-nitrophenyl)-1, 2, 3, 4-tetra- O -acetyl-β-d -glucuronamide: C20 H21 O12 ClN2 Ee = 100% [ α ]D 20 = +8.7 ( c 1, CHCl3 ) Source of chirality: synthesis 1, 2, 3, 4-Tetra- O -acetyl-β-d -glucuronic acid anhydride as starting material Abstract : N -(Naphthalene-1-yl)-1, 2, 3, 4-tetra- O -acetyl-β-d -glucuronamide: C24 H25 O10 N Ee = 100% [ α ]D 20 = +12.0 ( c 1, CHCl3 ) Source of chirality: synthesis 1, 2, 3, 4-Tetra- O -acetyl-β-d -glucuronic acid anhydride as starting material Abstract : N -(4-Bromo-naphthalene-1-yl)-1, 2, 3, 4-tetra- O -acetyl-β-d -glucuronamide: C24 H24 O10 NBr Ee = 100% [ α ]D 20 = −4.7 ( c 1, CHCl3 ) Source of chirality: synthesis 1, 2, 3, 4-Tetra- O -acetyl-β-d -glucuronic acid anhydride as starting material Abstract : N -(Indol-5-yl)-1, 2, 3, 4-tetra- O -acetyl-β-d -glucuronamide: C22 H24 O10 N2 Ee = 100% [ α ]D 20 = −10.3 ( c 1, CHCl3 ) Source of chirality: synthesis 1, 2, 3, 4-Tetra- O -acetyl-β-d -glucuronic acid anhydride as starting material Abstract : N -(Quinoxaline-6-yl)-1, 2, 3, 4-tetra- O -acetyl-β-d -glucuronamide: C22 H23 O10 N3 Ee = 100% [ α ]D 20 = −2.0 ( c 1, CHCl3 ) Source of chirality: synthesis 1, 2, 3, 4-Tetra- O -acetyl-β-d -glucuronic acid anhydride as starting material Abstract : N -(5-Bromo-quinoxaline-6-yl)-1, 2, 3, 4-tetra- O -acetyl-β-d -glucuronamide: C22 H22 O10 N3 Ee = 100% [ α ]D 20 = +12.3 ( c 1, CHCl3 ) Source of chirality: synthesis 1, 2, 3, 4-Tetra- O -acetyl-β-d -glucuronic acid anhydride as starting material Abstract : N -(Benzothiazol-2-yl)-1, 2, 3, 4-tetra- O -acetyl-β-d -glucuronamide: C21 H22 O10 N2 S Ee = 100% [ α ]D 20 = −9.3 ( c 1, CHCl3 ) Source of chirality: synthesis 1, 2, 3, 4-Tetra- O -acetyl-β-d -glucuronic acid anhydride as starting material Abstract : N -(6-Chloro-benzothiazol-2-yl)-1, 2, 3, 4-tetra- O -acetyl-β-d -glucuronamide: C21 H21 O10 ClN2 S Ee = 100% [ α ]D 20 = −8.4 ( c 1, CHCl3 ) Source of chirality: synthesis 1, 2, 3, 4-Tetra- O -acetyl-β-d -glucuronic acid anhydride as starting material Abstract : N -(6-Fluoro-benzothiazol-2-yl)-1, 2, 3, 4-tetra- O -acetyl-β-d -glucuronamide: C21 H21 O10 FN2 S Ee = 100% [ α ]D 20 = −11.8 ( c 1, CHCl3 ) Source of chirality: synthesis 1, 2, 3, 4-Tetra- O -acetyl-β-d -glucuronic acid anhydride as starting material Abstract : N -(6-Nitro-benzothiazol-2-yl)-1, 2, 3, 4-tetra- O -acetyl-β-d -glucuronamide: C21 H21 O12 N3 S Ee = 100% [ α ]D 20 = −5.1 ( c 1, CHCl3 ) Source of chirality: synthesis 1, 2, 3, 4-Tetra- O -acetyl-β-d -glucuronic acid anhydride as starting material