A Synthesis of Nordihydroguaiaretic Acid

Abstract

NotesVol. 69 hydrate. This crude material contained 96% of the theoretical electropositive chlorine content. When it was distilled at 76-78°(10 mm.) this chlorine content was found to be 99% of theoretical. The distilled product melted at 4-4.5°cor., á204 1.544. Since the crude material is sufficiently pure for most purposes, the distillation, which is dangerous, ought to be avoided. z-Propyldichloramine was prepared by a modification of the above procedures. To an ice-cooled concentrated aqueous solution of 95 g. (1 mole) of ¿-propylamine hydrochloride (prepared in situ) was added slowly 2.25 moles of aqueous sodium hypochlorite (prepared by adding chlorine to cold 15% aqueous sodium hydroxide, 1.6 moles hypochlorous acid per liter). Simultaneously with this addition over two to three hours was added 6 N hydrochloric acid at such a rate that the acidity was maintained between pH 5.6 and 6.6. Brom cresol green and chlorphenol red papers can be used as criteria if the solution is allowed to creep into the paper so as to give an indicator zone ahead of the bleached zone.After two hours' subsequent stirring in the cold, the heavy oil was separated, washed once with 50 cc. cold water, twice with 50-cc. portions of 5% sodium thiosulfate, once with cold water, twice with cold 50% sulfuric acid and finally twice with cold water. The crude yield (97 g., 76% of theoretical) contained 94% of the theoretical electropositive chlorine content.Distillation at 41-43°( 15 mm.) resulted in 70% recovery of yellow oil (d2tl41.165; n23d 1.4572) which contained 99.8% of the calculated electropositive chlorine content.

The Naturally Occurring Lignans

“…NDGA has also been synthesized by Lieberman, Mueller, and Stiller (204), who have patented their process (231). Their process involves the following I«]d = 0° (272) NDGA (from creosote bush).........................…”

Synthesis and bioactivity of erythro-nordihydroguaiaretic acid, threo-(-)-saururenin and their analogues

“…Hwu reported that NDGA and its analogues exhibited activity against HIV, and tetramethyl NDGA was a stronger anti-HIV agent. 17 Son et al developed a modified procedure for the synthesis of NDGA and related lignans. 13 NDGA, (-)-saururenin and their analogues have also been shown to have cancer chemopreventive properties.…”

Facile Total Synthesis of Isopregomisin

“…HCI (10%) to remove the pyridine. The standard ethereal workup followed by purification by FCG afforded the desired product 8 as a white solid (1.2 g, 95%): mp 78-80°C; mlz (ElMS) 318, 316 (M+), 276, 237 (6) Isopregomisin I.-To the Grignard reagent made from magnesium turnings (72 mg, 3 mmol) and compound 8 (640mg, 2 mmol) in dry THF (10 ml) was added dropwise a solution of (E)-2-tert-butyl-3- Our synthetic strategy (outlined in Scheme I) started from pyrogallol 2, which was easily converted into trimethyl pyrogallol 3. Treatment of 3 with ZnCl 2/propionic acid gave 2,6-dimethoxyphenol (4) in a yield of 71%.…”