Sclareol oxide

A simple approach to sclareol oxide has also been reported [114]. 

In two syntheses of the diol (41), the sclareol (3) has been used as a starting compound. The sclareol oxidation product, the sclareol oxide (82) [61], on bromination in methanol afforded the dibromomethoxy derivative (83) which on interaction with potassium hydroxide eliminated hydrogen bromide, giving the unsaturated oxide (84). Its successive ozonolysis and reduction of the ozonolysis products with LiAlH4 led to drimane-8a,ll-diol (41). The overall yield of the diol (41) from the sclareol (3) was ca 32% [62] (Scheme 13). 

Schumacher, J.N. Turkish tobacco. The molecular dis-tiUation of Turkish tobacco extract. The isolation of two tobacco flavorant precursors (sclareol oxide and Compound XXIII) RDR, 1962, No. 3, January 12, see www.ijrtdocs.com 500938648 -8668. 

Compounds (308) to (311), which are considered to be breakdown flavors from labdane diterpenoids, were also exclusively found in Oriental-type tobaccos. Nor-ambreinolide (308), obtained for the first time from Manila cigar-type tobacco (284), its hemi-acetal and dehydro derivative (309), sclareol oxide (310), the unsaturated hydroxyketone (311) (75) and the drimane metabolite (238) (556) impart a pleasant cedar-like odor which is detectable to some extent in the cigarette package but is particularly detectable and pleasing in the mainstream and sidestream smokes when the cigarette is smoked (556). 

The fragrance (-)-Ambrox (a commercial substitute for ambergris from the blue sperm whale) was made by oxidation of (-)-sclareol (1) with RuClj/aq. Na(IO )/ CC1 -CH3CN/40°C a mixture of (+)-sclareolide (2) with the (-)-acetoxy acid... 

In addition to linalyl acetate, the oil contains linalool and other terpene alcohols, as well as their acetates. When the volatile components are evaporated, a distinct ambergris note develops that is attributed to oxidative degradation products of sclareol [515-03-7] [746-750a]. Sclareol is the main component in the concrete, obtained by solvent extraction of S. sclarea L. leaves [750b]. 

The aerial parts of Conyza steudellii (Asteraceae) have given new labdane xylosides, while from the leaves of Conyza trihecatactis, a xylopyranoside of 13-epi-sclareol has been isolated among other labdanes [104,105]. Havardic acids A-F (as methyl esters), have been isolated from another genus of the Asteraceae family, i.e Grindelia havardii [106]. 11-oxo-manoyl oxide derivatives and coleosol, which is also a manoyl oxide derivative, have been obtained from Coleus forskohlii (Labiateae) [107,108] while from another plant of the Labiatae family, Roylea calycina a tumor inhibitory compound, namely precalyone, as well as calyone have been isolated [109]. 

Manoyl oxide (4), Fig. (7), has been isolated as a pure compound or identified via analytical techniques, in several plant species [33,44,63,137, 138,139]. Ohloff has shown that manoyl oxide can be prepared from sclareol [140]. The physical and chromatographic data of the synthetic and of the natural manoyl oxides have been compared and discussed [141]. Hodges and Reed have substantially contributed to the knowledge of the stereochemistry of manoyl oxide [141]. 

Data submitted for publication. The study concerns the effect of the thiomidazolide derivative of enf-3p-hydroxy manoyl oxide and of sclareol on the expression of the two oncogenes in two leukemic cell lines, where an apoptotic effect was also observed... 

Compounds based on manool and sclareol have been studied for perfumery purposes for many years. The conversion of manoyl oxide (5 R = H2) and its... 

Composition The European Pharmacopoeia lists linalyl acetate (56-78%), linalool (6.5-24%) and germacrene D (1.0-12%). a-Terpineol is limited to 5.0%, a- and P-thujone to 0.2%. Sclareol (0.4-2.6%) is found mainly in the concrete and is used for the synthesis of ambra fragrance materials. Further constituents are linalool oxide, geraniol, nerol, neryl and terpinyl acetate, citronellol, 1,8-cineole, benzaldehyde and n-nonanal. For further literature see [64, 65]. 

The formation of a common manool trihydrochloride from manool, sclareol, manoyl oxide, 13-epimanoyl oxide, biformene, and abienol played an important part in the structural correlation between these diterpenes. Earlier proposals had suggested an 8-equatorial chlorine atom, but in a paperclarifying the various 8,13,15-chloro-labdanes, the analogous monohydrochloride from tetra-hydroabienol was assigned the 8-axial stereochemistry (8). Dehydrochlorination of this isomer yields all three expected olefins, whilst the equatorial epimer affords only the and A -olefins. 

A shorter synthesis of the drimenyl acetate (12) was elaborated by Barrero et al. [42] from the sclareol (3) (Scheme 7). Oxidative cleavage of... 

In the other synthesis of the diol (41) from the sclareol (3) [63], the latter was ozonised according to [64], Under these conditions, a mixture of C-12 epimeric bisnorlabdanic oxidoketones (85) has been formed in a high yield. Its oxidation with monoperphtalic acid afforded a mixture of acetoxy oxides (75), from which acetic acid has been eliminated to give the unsaturated oxide (76). The latter was ozonised and the ozonolysis products were reduced with NaBffr into the diol (41). This four-step synthesis led to the diol (41) in an overall 44% yield (Scheme 14). 

Labdane and pimarane type diterpenoids are rather rare in Turkish Sahna species, and only a few of these compounds have been obtained. Sclareol and manool were isolated from S. scktred. Manool was also obtained from S.limbaia, while manoyl oxide was reported from S. camlidissiiru/ together with 11 P-hydroxymanoyl oxide and 8,13-di-e/rr-manoyl oxide . Although these two compounds were... 

Some empirical uses of S. sclarea suggest that its essential oil, like many essential oils of the Lamiaceae family, has an inhibitory effect on microorganisms pathogenic to man. Ulubelen et al. [51] examined the antimicrobial activity of some diterpenes and sesquiterpenes found in an acetone extract of S. sclarea. They found that 2, 3-dehydrosalvipisone, sclareol, manool, 7-oxoroyleanone, spathulenol and caryophyllene oxide were active against Staphylococcus aureus 2, 3- dehydrosalvipisone and manool were active against Candida albicans and caryophyllene oxide was active against Proteus mirabilis. 

The advantages of this synthetic approach lie in the availability of the feedstock and the fact that enantio-pure material is produced. However, the processes also have some serious disadvantages. The oxidation of sclareol (8.15) requires the stoichiometric use of either chromium or manganese salts. This leads to a serious effluent problem. The oxidation... 

The cyclization reactions of manool derivatives have continued to attract attention. A synthesis of the strobane skeleton based on oxymercuration reactions of 13-epimanool has been described. The oxidation of sclareol by chromium salts has been re-examined in a series of papers. The circular dichroism curves of manoyl oxide and its 13-epimers have been examined. Some further 11-oxomanoyl oxide derivatives, coleonol E and F, (13) and (14),... 

The key step in the industrial partial synthesis of (-)-Ambrox is the oxidative deavage of the side-chain of sclareol, either by oxidation with chromium trioxide or by potassium permanganate, followed by ozonolysis. 

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