124605-71-6

Upstream product

• 1050512-02-1 nordihydroguairetic acid 
• 77-78-1 dimethyl sulfate 
• 621-59-0 isovanillin 
• 6346-05-0 3-benzyloxy-4-methoxybenzaldehyde 
• 124605-68-1 C₃₄H₃₈O₄S₂ 
• 55890-23-8 threo-austrobailignan-5 

Relevant academic research and scientific papers

Ring substitution influences oxidative cyclisation and reactive metabolite formation of nordihydroguaiaretic acid analogues

Nordihydroguaiaretic acid (NDGA) is a natural polyphenol with a broad spectrum of pharmacological properties. However, its usefulness is hindered by the lack of understanding of its pharmacological and toxicological pathways. Previously we showed that oxidative cyclisation of NDGA at physiological pH forms a dibenzocyclooctadiene that may have therapeutic benefits whilst oxidation to an ortho-quinone likely mediates toxicological properties. NDGA analogues with higher propensity to cyclise under physiologically relevant conditions might have pharmacological implications, which motivated this study. We synthesized a series of NDGA analogues which were designed to investigate the structural features which influence the intramolecular cyclisation process and help to understand the mechanism of NDGA's autoxidative conversion to a dibenzocyclooctadiene lignan. We determined the ability of the NDGA analogues investigated to form dibenzocyclooctadienes and evaluated the oxidative stability at pH 7.4 of the analogues and the stability of any dibenzocyclooctadienes formed from the NDGA analogues. We found among our group of analogues the catechols were less stable than phenols, a single catechol-substituted ring is insufficient to form a dibenzocyclooctadiene lignan, and only compounds possessing a di-catechol could form dibenzocyclooctadienes. This suggests that quinone formation may not be necessary for cyclisation to occur and the intramolecular cyclisation likely involves a radical-mediated rather than an electrophilic substitution process. We also determined that the catechol dibenzocyclooctadienes autoxidised at comparable rates to the parent catechol. This suggests that assigning in vitro biological activity to the NDGA dibenzocyclooctadiene is premature and requires additional study.

Antiviral activities of methylated nordihydroguaiaretic acids. 1. Synthesis, structure identification, and inhibition of Tat-regulated HIV transactivation

Nordihydroguaiaretic acid (NDGA, meso-1) possesses four phenolic hydroxyl groups. Treatment of NDGA with 0.50-4.1 equiv of dimethyl sulfate and 3.0-6.0 equiv of potassium carbonate in acetone at 56 °C gave nine methylated products. Eight of those mono-, di-, tri-, and tetra-Omethylated NDGAs were isolated in pure form, and their structures were identified unambiguously by spectroscopic methods. A preparative amount of tetramethyl NDGA M4N (10) was obtained in 99% yield from NDGA by use of 4.1 equiv of dimethyl sulfate for the methylation. Among the eight different methylated NDGAs (2-6 and 8-10), tetra-O-methyl-NDGA (10) showed the strongest anti-HIV activity (IC50 11 μM). Chemically synthesized 3'-O-methylNDGA ((±)-2) showed identical anti-HIV activity (IC50 25 μM) to the lignan isolated from Creosote Bush. Lignans with methylated catecholic hydroxyl groups can be produced in large quantities with low cost. At drug concentrations below 30 μM, tetramethyl NDGA (10) was a stronger anti-HIV agent than mono- and dimethylated NDGAs.

Regioselective Cleavage of the Methylenedioxy Group: Conversion of (-)-Austrobailignan-5 to (-)-Dihydroguaiaretic Acid

A method for the selective cleavage of a benzodioxole (methylenedioxy group) to a methoxyphenol through the use of a p-methylthiophenoxide ion is described.When the procedure was applied to a lignan derivative such as (-)-austrobailignan-5, the reaction w