Phytol synthesis

Phytol [505-06-5] (111) and isophytol [150-86-7] (112) are important intermediates used in commercial synthesis of Vitamins E and K. There is a variety of synthetic methods for their manufacture. Chlorophyll [479-61-8] is a phytyl ester. 

Although all four tocopherols have been synthesized as their all-rac forms, the commercially significant form of tocopherol is i7//-n7i a-tocopheryl acetate. The commercial processes ia use are based on the work reported by several groups ia 1938 (15—17). These processes utilize a Friedel-Crafts-type condensation of 2,3,5-trimethylhydroquinone with either phytol (16), a phytyl haUde (7,16,17), or phytadiene (7). The principal synthesis (Fig. 3) ia current commercial use iavolves condensation of 2,3,5-trimethylhydroquiQone (13) with synthetic isophytol (14) ia an iaert solvent, such as benzene or hexane, with an acid catalyst, such as ziac chloride, boron trifluoride, or orthoboric acid/oxaUc acid (7,8,18) to give the all-rac-acetate ester (15b) by reaction with acetic anhydride. Purification of tocopheryl acetate is readily accompHshed by high vacuum molecular distillation and rectification (<1 mm Hg) to achieve the required USP standard. 

Wharton, P.S. and Nicholson, R.L., Temporal synthesis and radiolabelling of the sorghum 3-deoxyanthocyanidin phytoalexins and the anthocyanin, cyanidin 3-dima-lonyl glucoside, New Phytol, 145, 457, 2000. 

In addition to its role as an intermediate in cholesterol biosynthesis, isopentenyl pyrophosphate is the activated precursor of a huge array of biomolecules with diverse biological roles (Fig. 21-48). They include vitamins A, E, and K plant pigments such as carotene and the phytol chain of chlorophyll natural rubber many essential oils (such as the fragrant principles of lemon oil, eucalyptus, and musk) insect juvenile hormone, which controls metamorphosis dolichols, which serve as lipid-soluble carriers in complex polysaccharide synthesis and ubiquinone and plastoquinone, electron carriers in mitochondria and chloroplasts. Collectively, these molecules are called isoprenoids. More than... 

The synthesis of Vitamin E, that is, a-tocopherol (5,7,8-trimethyltocol) in the past has been accomplished primarily by reacting trimethylhydroquinone (TMHQ) with isophytol (3,7,ll,15-tetramethylhexadec-l-en-3-ol) or phytol (3,7,ll,15-tetramethylhexadec-2-en-l-ol) in a condensation reaction. The reaction is well known and has been practiced for many years (Stalla-Bourdillon, Ind. Chim. Belg., 35, 13 (1970) "The Vitamins" Vol. 5, pages 168-223, Academic Press, New York, 1967). 

The condensation of allylic alcohols with phenolic compounds in the presence of an acid catalyst yields allylphenols. This reaction was used 86 in a synthesis of vitamin K (LXXVa) by condensing phytol with 2-methyl-l,4-naphthohydroquinone in dioxane with oxalic or trichloroacetic acid as catalyst the hydroquinone first formed was oxidized to... 

Nagaraj, V.J., Altenbach, D., Galati, V., Luscher, M., Meyer, A.D., Boiler, T., and Wiemken, A., Distinct regulation of sucrose sucrose-l-fructosyltransferase (1-SST) and sucrose fructan-6-fructosyltrans-ferase (6-SFT), the key enzymes of fructan synthesis in barley leaves 1-SST as the pacemaker, New Phytol., 161, 735-748, 2004. 

Oxidation reactions of this nature are common in the literature. For example, selenium dioxide in refluxing etiumolic solution brought about the allylic oxidative rearrangement geranyl acetate, which was further functionalized in a synthesis of the norsesquiterpenoid gytinidal (equation 46). This trans formation was also used in a total synthesis of phytol. Similarly, an a, -unsaturated aldehyde was obtained undm similar conditions in studies of a synthesis of pentalenic acid derivatives (equation 47). ... 

Reactions in SCCO2 have also been used for the production of minor lipid components, such as tocopherols and sterol esters. The synthesis of D, L, ot-tocopherol in SCCO2 and nitrous oxide by condensation of trimethyUiydroquinone with iso-phytol in the presence of various Bronsted or Lewis acids as catalysts resulted in... 

In methodology developed by Fieser, unprotected menadiol (5) was condensed with natural phytol using oxaHc acid as catalyst (25). Oxidation of the hydroquinone to the naphthoquinone yielded vitamin K. A similar approach has been reported (26). The commercial synthesis of vitamin is largely based on the above with some important improvements from Roche (27) and Merck (28). 

Dehydrative condensation. Hirschmann, Miller, and Wendler developed an improved synthesis of vitamin Ki involving condensation of phytol with the 1-mono-acetate of 2-methyl-1,4-naphthohydroquinone in dioxane at 76° in the presence of... 

Phytol, CAS no. [150-86-7] C20H40O, an alcohol obtained by the decomposition of chlorophyll is an odorless liquid, BP 202—204°C/10mm Hg and has been used in the synthesis of vitamin E. On reaction with trimethyl hydroquinone phytol is converted to a-tocopherol, etc. 

The a,P-unsaturated nitriles can be converted to the corresponding a,P-unsaturated alcohols by two successive treatments with DlBAL-H. This reaction has been used in the synthesis of sarco-phytols A and T to produce the allylic alcohol in 71% yield " ... 

Takayanagi, H., Kitano, Y., and Morinaka, Y, Stereo- and enantioselective total synthesis of sarco-phytol A, Tetrahedron Lett., 31, 3317, 1990. 

Bony S, Pichon N, Ravel C, Durix A, Balfourier F, Guillaumin JJ. The relationship between mycotoxin synthesis and isolate morphology in fungal endophytes of Lolium perenne. New Phytol 152 125-137, 2001. 

Amongst the few reported reactions of oxetans is their non-stereospecific conversion into oxazines when treated with nitriles and the reaction of the (R)-lactone (44) with a Grignard reagent as the key step in a novel synthesis of (i ,/ )-phytol. ... 

Pristane, 2,6,10,14-Tetramethylpentadecane nor-phytane Robuoy. C. H mol wt 268.51. C 84,98%, H 15.02%. Isoprenoid alkane obtained from the unsaponifiable fraction of shark liver oil where it occurs to an extent of 14% Tsujimoto. J. Soc. Chem. Ind. 51, 3 7T (1932) Sorensen, Mehllum, Acta Chem. Scand. 2, 140 (1948). Identity with norphytane Pliva, Sorensen, ibid. 4, 846 (1950), Isoln from patroleum crude oils Bendoraitis et al. Anal Chem. 34, 49 (1962) from wool wax Mold et al. Nature 199, 283 (1963). Synthesis from phytol Sorensen, Sorensen, Acta... 

Toco], 3,4-Dihydro-2-methyl-2-(4.8.I2-trimethyl-tridecyl)-2H-l-bentopyran-6-oi 2-methyl-2-(4,8, 12-tri-me(hyltridecyl)-6-chromanoi 2-methyl -2-phytyl-6-chroma-nol 6-hydroxy-2-methyl-2-phytylch roman 2-methyl 2 phytyl-6-hydroxychroman. C H O, mol wt 388.61. C 80,35%, H 11.41%, O 8.23%. Synthesis by the condensation of hydroquin one and phytol in the presence of anhydr formic acid Pendse, Karrer, Helv. Chim. Acta 48, 1837 (1957). Antioxidant activity of tocol and its methyl derivS Olcott, van der Veen, Lipids 3, 331 (1968),... 

Reformatsky reactions have been used in the total synthesis of various important natural products such as phytol,225 naturally occurring polyenes,226 and vitamin A (from / -ionylideneacetaldehyde).227... 

It appears probable that the relative biological activity of the final synthesised a-tocopherol and the cost of the particular synthesis would be intimately involved in a cost/benefit exercise in the choice between a synthetic route for the C20 intermediate or the use of natural phytol. 

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