Miltirone isolation

Attempts to hydrolyse the ester 2 with either KOH/IfyO/MeOH at 50°C or LiOH/THF/IfyO at reflux or AcOH in quinoline at 120°C were unsuccessful, and the starting material was recovered unchanged. Use of KO Bu/DMSO at 40-60°C for 4 hours, however, followed by aqueous acid gave a mixture of four products, the major of which (80%) was shown to be the acid 3. Ether cleavage of 3 with BBr3/CH2Cl2 at room temperature proceeded rapidly (5 min), and while the catechol derivative could be isolated and characterised spectroscopically, it was rapidly oxidised in air to 4, the potent benzodiazepine agonist miltirone. 

Tanshen (Salvia miltiorrhiza Bung), a medicinal plant, has been used in traditional Chinese medicine for its tranquilizing, sedative, circulation-promoting and bacteriocidal effects. [73], It has proven to be a rich source of abietane o-quinone diterpenoids. Miltirone (197) is a tricyclic diterpenoid quinone which has been isolated from the roots of salvia miltiorrhiza Bung. The isolation of miltirone constitutes a new addition to naturally occurring quinines related to tanshinones [74,75] isolated from the same source. 

Dry clean tanshen rhizomes were powdered and extracted with hexane for three days at room temperature. The hexane solution was kept overnight and then filtered. After removal of the solvent a residue was obtained which was separated into seven colored fractions by column chromatography with silica gel. Miltirone was isolated by preparative tic from fraction 1 (light red) using hexane ethyl acetate (4 1) followed by benzene-acetone (20 1). The product obtained was recrystallized from ethylacetate, m.p. 100-101°C. Its structure was confirmed by mass spectrum, NMR, IR and UV spectra which agree quite closely with those of Ho et al [76], Miltirone showed antioxidant behavior comparable to that of the commonly used phenolics BHT and BEA [77], The antioxidant activity of miltirone in lard at 100°C was determined with a Rancimat. Miltirone and other related compounds may have the potential of being used as natural antioxidants in food and cosmetics. 

O-quinone (199) prepared from catechol (198) was heated with vinylcyclohexene (200) in refluxing ethanol. Miltirone (197) was isolated by column chromatography in 28-30% yield. About 5% of (200) could be recovered Lower temperatures or longer reaction times damaged the reaction. 

The dried roots of Salvia miltiorrhiza form the Chinese drug tan-shen , from which a number of furanonaphthoquinones-the tanshinones, isotanshinones, and cryptotanshinones-have been isolated. The roots also contain an o-naphtho-quinone, miltirone, whose structure (34) was assigned on the basis of its spectral properties and the formation of a triacetate which on hydrolysis and oxidation gave a hydroxy-1,4-naphthoquinone. 

The wild herb Tanshen Salvia miltiorrhiza Bunge) has been used in traditional Chinese medicine because of its sedative and tranquilizing effects and is also being used to treat coronary heart disease and insomnia. Me range of diterpenoid quinones and quinone precursors have been isolated from Tanshen, including miltirone (56), also known as rosmariquinone, one of the antioxidant components of rosemary (Figure 5.2). °... 

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