New series of N-aryl- and N-heteroaryl-d-glucuronamides as potential anticancer agents: synthesis and spectroscopic analysis

A series of structurally diverse d-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-substituted d-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.

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1,2,3,4-Tetra-O-acetyl-β-d-glucuronic acid anhydrideC16H20O12Ee = 100%[α]D20 = +5.4 (c 1, CHCl3)Source of chirality: synthesisd-Glucuronic acid as starting material

N-(4-Nitrophenyl)-1,2,3,4-tetra-O-acetyl-β-d-glucuronamideC20H22O12N2Ee = 100%[α]D20 = −1.3 (c 1, CHCl3)Source of chirality: synthesis1,2,3,4-Tetra-O-acetyl-β-d-glucuronic acid anhydride as starting material

N-(4-Chloro-3-nitrophenyl)-1,2,3,4-tetra-O-acetyl-β-d-glucuronamideC20H21O12ClN2Ee = 100%[α]D20 = +8.7 (c 1, CHCl3)Source of chirality: synthesis1,2,3,4-Tetra-O-acetyl-β-d-glucuronic acid anhydride as starting material

N-(Naphthalene-1-yl)-1,2,3,4-tetra-O-acetyl-β-d-glucuronamideC24H25O10NEe = 100%[α]D20 = +12.0 (c 1, CHCl3)Source of chirality: synthesis1,2,3,4-Tetra-O-acetyl-β-d-glucuronic acid anhydride as starting material

N-(4-Bromo-naphthalene-1-yl)-1,2,3,4-tetra-O-acetyl-β-d-glucuronamideC24H24O10NBrEe = 100%[α]D20 = −4.7 (c 1, CHCl3)Source of chirality: synthesis1,2,3,4-Tetra-O-acetyl-β-d-glucuronic acid anhydride as starting material

N-(Indol-5-yl)-1,2,3,4-tetra-O-acetyl-β-d-glucuronamideC22H24O10N2Ee = 100%[α]D20 = −10.3 (c 1, CHCl3)Source of chirality: synthesis1,2,3,4-Tetra-O-acetyl-β-d-glucuronic acid anhydride as starting material

N-(Quinoxaline-6-yl)-1,2,3,4-tetra-O-acetyl-β-d-glucuronamideC22H23O10N3Ee = 100%[α]D20 = −2.0 (c 1, CHCl3)Source of chirality: synthesis1,2,3,4-Tetra-O-acetyl-β-d-glucuronic acid anhydride as starting material

N-(5-Bromo-quinoxaline-6-yl)-1,2,3,4-tetra-O-acetyl-β-d-glucuronamideC22H22O10N3Ee = 100%[α]D20 = +12.3 (c 1, CHCl3)Source of chirality: synthesis1,2,3,4-Tetra-O-acetyl-β-d-glucuronic acid anhydride as starting material

N-(Benzothiazol-2-yl)-1,2,3,4-tetra-O-acetyl-β-d-glucuronamideC21H22O10N2SEe = 100%[α]D20 = −9.3 (c 1, CHCl3)Source of chirality: synthesis1,2,3,4-Tetra-O-acetyl-β-d-glucuronic acid anhydride as starting material

N-(6-Chloro-benzothiazol-2-yl)-1,2,3,4-tetra-O-acetyl-β-d-glucuronamideC21H21O10ClN2SEe = 100%[α]D20 = −8.4 (c 1, CHCl3)Source of chirality: synthesis1,2,3,4-Tetra-O-acetyl-β-d-glucuronic acid anhydride as starting material

N-(6-Fluoro-benzothiazol-2-yl)-1,2,3,4-tetra-O-acetyl-β-d-glucuronamideC21H21O10FN2SEe = 100%[α]D20 = −11.8 (c 1, CHCl3)Source of chirality: synthesis1,2,3,4-Tetra-O-acetyl-β-d-glucuronic acid anhydride as starting material

N-(6-Nitro-benzothiazol-2-yl)-1,2,3,4-tetra-O-acetyl-β-d-glucuronamideC21H21O12N3SEe = 100%[α]D20 = −5.1 (c 1, CHCl3)Source of chirality: synthesis1,2,3,4-Tetra-O-acetyl-β-d-glucuronic acid anhydride as starting material