Squalene-2,3-diol

This sterol has been used to resolve squalene-2,3-diol by way of the dia-stereoisomeric esters. ... 

The isoprenoid polyenes famesyl acetate, geranyl acetate and squalene underwent oxidative poly cyclisation to bis-, tris- and penta-tetrahydrofurans with RuO /aq. Na(IO )/CH3CN-EtOAc [185]-[188]. This oxidative polycyclisation of squalene with RuO was shown to lead to the cis-threo-cis-threo-trans-threo-trans-threo-trans penta-tetrahydrofuranyl diol product, this configuration being determined by 2D-NMR (Fig. 3.14) [185]-[188] cf mech. Fig. 1.8 [185]. 

Double Sharpless epoxidation was applied to the syntheses of both enantiomers of 2,3 22,23-diepoxy squalene-l,24-diol, 8a and 8b, in 58% and 37% yields, respectively.3 Tetradeuterated... 

Squalene (48) presents an interesting array of trisuhstituted double honds with which to test the selectivity of catalytic AD. Osmium tetroxide catalyzed dihydroxylation of squalene in the absence of a chiral ligand generates a mixture of the 2,3-diol (49), 6,7-diol (50), and 10,11-diol (51) in a ratio of 1 1 1. (Squalene is used in excess in these experiments to minimize multiple-dihydroxylations of the squalene molecule.) Dihydroxylation with (DHQD)2-PHAL as the chiral ligand produces the diols 49, 50, and 51 in a ratio of 46 35 19. Stereochemical analysis of the 2,3-diol (49) indicates formation of the 2,3/ -diol with 96% ee [57a], Perhydroxylation of squalene has also been achieved with 98% ee or de for each of the six dihydroxylation events required in the process [57b]. 

AD of 2,6- , -famesyl acetate (3) with 8 as ligand occurred selectively at the terminal double bond to give 5 with 96% ee (position selectivity of about 120 1). In a special solvent system consisting of /ert-butanol-water-methylcyclohexane, at ca. 50% conversion of squalene (4) diol 6 was obtained in 32% yield with 90% ee. Here, the position selectivity was 8 1 [51. 

Johnson et al. used their newly developed orthoester Claisen reaction to achieve a highly stereoselective total synthesis of aM-trans squalene (5)1 (Scheme 1.20. The diene diol 6 underwent Johnson-Claisen rearrangement when it was heated with ethyl orthoacetate in the presence of propionic acid for 3 h at 138 C. The diene dialdehyde 7, obtained by treatment of the resulting ester with lithium aluminum hydride followed by oxidation with Collins reagent, reacted with 2-propenyllithium to give the tetraene diol 8. The tetraene dialdehyde 9, which... 

Oxidative polycyclizations with, for example, RuOa catalysts can be carried out with polyene substrates as complex as farnesyl acetate, geranylgeranyl acetate, and squalene. The f , f , /ra j,/ra r,/ra r-configuration of the penta-tetrahydrofuranyl diol product resulting from the oxidation of squalene (Scheme 57) has been determined by nuclear magnetic resonance (NMR) spectroscopy <2005T927>. 

An enzyme system from the yeast Saccharomyces cerevisiae is able to incorporate isoprenoid precursors into the C30 phytoene analogue (200) only in the presence of Mn and absence of NADPH. If NAD PH is present and Mn is replaced by Mg, the sterol precursor squalene (201) is produced.The substrate specificity of the chloroplast enzyme violaxanthin deepoxidase has been examined.In addition to the normal substrate violaxanthin [(35,5/ ,65,3 5,5 i ,6 5)- 5,6,5, 6 -diepoxy-5,6,5, 6 -tetrahydro-/3,j8-carotene-3,3-diol, (196)] several all-trans-monoepoxy-carotenoids, such as anthera-xanthin [5,6-epoxy-5,6-dihydro-/3,/3-carotene-3,3 -diol (197)], diadinoxanthin [5,6-epoxy-7, 8 -didehydro-5,6-dihydro-j8, 8-carotene-3,3 -diol (198)], and /3-cryptoxanthin epoxide [5,6-epoxy-5,6-dihydro-/3,/3-caroten-3-ol (199)], all with the 38,5R,6S) configuration, were utilized. Violeoxanthin (9-cis-violaxanthin) and other 9-cis-isomers were not affected. A carrot Daucus carota) tissue culture has been shown to incorporate [ C]acetate into carotenoids. ... 

Diol (165) is an intermediate in the synthesis of the symmetrical triterpene, squalene (167). Succin-dialdehyde serves as the central four carbons followed by bidirectional synthesis through diol (164). The transformation of diol (164) into its higher homolog (165) requires several operations (i) orthoacetate rearrangement s to a diester (ii) reduction to a diol (iii) oxidation to a dialdehyde and (iv) addition of iso-propenyllithium. A more convergent approach employs 3,3-dimethoxy-2-methylbut-l-ene in conjunction with diol (164), a sequence that only requires reduction of the resultant isopropenyl ketone after rearrangement to realize diol (165). ... 

Italian and Spanish ohve oil from the 1991-1992 crop year contained a very high level of 9,19-cyclolanosterol (>400 mg/kg), which was not found with the standard method for sterol analysis. Two isomers of this sterol were identified by GC/MS of the unsaponifiable fraction, and their levels were found to be inversely proportional to the levels of p-sitosterol in the oils. GC/MS of the unsaponifiable fraction with high-resolution GC capillary columns provides a relatively rapid means of checking product purity and the identity of individual components. Thus, triterpene diols were identifiable at m/z 203, ot-tocopherol at m/z 165, squalene at m/z 69, cholesterol at m/z 386, and brassicasterol, characteristic of canola oil and other Brassica oils, at m/z 398. 

A convenient synthesis of optically active squalene 2,3-oxide from L-glutamic acid has been reported.The (5)-acetonide (1), derived from glutamic acid, was converted by standard methods into the C30 compound (2). The corresponding diol (3) was transformed," via the mesylate (4), into (3i )-squalene 2,3-oxide (5). Hydrolysis of (5), mesylation, and displacement afforded the enantiomeric (35)-oxide (6). 

The isotopic analyses applied to the water samples derived from the Lippe river longitudinal profile comprised main contaminants as illustrated above and described intensively in chapter 3.1.1. In detail stable carbon isotope ratios of tri-n-butyl phosphate (TBP), tris(chloroethyl)phosphate (TCEP), 2,4,7,9-tetramethyl-5-decyne-4,7-diol (TPDB), di- -butylphthalate, bis(2-ethylhexyl)phthalate (DEHP), galaxolide, tonalide, and squalene were determined. Further on, the internal standard d34-hexadecane was analysed simultaneously. Noteworthy, several compounds presented were also determined in the Rhine river samples. All results are summarized in Figure 7. 

During the oxidative decarbonylation, the 15a-hydrogen is lost. Also, if squalene is converted to cholesterol in HjO, the 15 position of cholesterol is labeled. This led to the suggestion that C-15 was hydroxylated and that a 4,4-dimethyl-14a-formyl-cholest-7-ene-3)8,15-diol was the substrate for the oxidative decarbonylation. Several 15a-hydroxy sterols have been tested as precursors. One did not work, the other was converted only poorly [105]. The double bond at C-14 is probably reduced as the next step since A sterols are rarely encountered. NADPH would be a probable reductant. 

The synthesis of all-rrrwx-squalene has also been performed with diol 14 by the ortho ester variant224. 

The resolution of synthetic presqualene and prephytoene alcohols via their etienic acid derivatives has been reported. This work confirmed that the active (-f-)-enantiomers in both series have the same absolute configuration [(li , 2/ , 3/ )]. It has been established, by use of Hn.m.r., that the proton (deuteron) introduced at C-3 during the cyclization of squalene to tetrahymanol by Tetrahymena pyriformis has the 3/8 configuration. Both antipodes of the trimethyldecalol (13) have been shown to be effective inhibitors of cholesterol biosynthesis in rat liver enzyme preparations and cultured mammalian cells. The accumulation of squalene 2,3-oxide and squalene 2,3 22,23-dioxide in the treated systems indicates that inhibition occurs at the cyclization stage. The inhibitor is metabolized to the diol (14). The results of other sterol inhibition... 

A second new synthesis of squalene utilizes the observation that selenium dioxide oxidation of gem-dimethyl olefins or cis- and truns-allylic alcohols yields stereospecifically traus-aj3-unsaturated aldehydes. The olefin (4) or a mixture of cis- and truus-diols (5) were transformed by use of selenium dioxide, followed by reduction, into the truns-allylic diol (6). The corresponding bromide (7) was used to alkylate two moles of the ylide from trans-geranyltributylphosphonium bromide leading eventually to all-traus-squalene in 46% yield [from the diol (6)]. Protection of one of the p-alcohol groups of (6) as the tetrahydropyranyl ether opens the possibilities of unsymmetrical coupling and the introduction of specifically labelled fragments. 

The resulting motif of cis-configurated THF diols can be found in a remarkable number of natural products of different classes, e.g., annonaceous acetogenins such as cis-sylvaticin or membraroUin, polyether antibiotics such as monensin A, and squalene-derived metabolites such as glabrescol (Fig. 2) [25-30]. 

Harding WW, Lewis PA, Jacobs H, Mclean S, Reynolds WF, Tay LL, Yang JP (1995) Glabrescol - A Unique Squalene-Derived Penta-THF Diol from Spathelia glabrescens (Rutaceae). Tetrahedron Lett 36 9137... 

Waxes in general can contain a wide range of different compounds, including aliphatic diols, free alcohols, hydrocarbons (especially squalene), aldehydes, ketones, hydroxy-ketones, p-diketones and sesquiterpenes. The composition and biochemistry of waxes in nature, and methods for their analysis, have been reviewed in a comprehensive monograph [491],... 

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