beta-Sitosterol
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| Names | |
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| IUPAC name
Stigmast-5-en-3β-ol
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| Systematic IUPAC name
(1R,3aS,3bS,7S,9aR,9bS,11aR)-1-[(2R,5R)-5-Ethyl-6-methylheptan-2-yl]-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[a]phenanthren-7-ol | |
| Other names
22,23-Dihydrostigmasterol, β-Sitosterin
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| Identifiers | |
3D model (JSmol)
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| ChEBI | |
| ChEMBL | |
| ChemSpider | |
| ECHA InfoCard | 100.001.346 |
PubChemCID
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| UNII | |
CompTox Dashboard(EPA)
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| Properties | |
| C29H50O | |
| Molar mass | 414.718g·mol−1 |
| Melting point | 136 to 140 °C (277 to 284 °F; 409 to 413 K)[1] |
Except where otherwise noted, data are given for materials in theirstandard state(at 25 °C [77 °F], 100 kPa).
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β-sitosterol(beta-sitosterol) is one of severalphytosterols(plant sterols) withchemical structuressimilar to that ofcholesterol.It is a white, waxy powder with a characteristic odor, and is one of the components of thefood additiveE499.Phytosterols are hydrophobic and soluble in alcohols.
Natural occurrences and food
[edit]β-sitosterol is widely distributed in theplant kingdom.It is found invegetable oil,nuts,avocados,and derived prepared foods such assalad dressings.[2]Olavius algarvensis,a species of marine annelid, predominantly incorporate sitosterol into their cell membranes instead of cholesterol, though cholesterol is also present in said membranes.[3]
Human research
[edit]β-sitosterol is being studied for its potential to reducebenign prostatic hyperplasia(BPH)[4][5]and bloodcholesterollevels.[6]
Genetic disorder
[edit]While plant sterols are usually beneficial, there is a rare autosomal recessive genetic disorderphytosterolemiawhich causes over-absorption of phytosterols.[7]
Precursor of anabolic steroid boldenone
[edit]Being a steroid, β-sitosterol is a precursor of anabolic steroidboldenone.Boldenone undecylenateis commonly used in veterinary medicine to induce growth in cattle but it is also one of the most commonly abused anabolic steroids in sports. This led to suspicion that some athletes testing positive on boldenone undecylenate did not actually abuse the hormone itself but consumed food rich in β-sitosterol.[8][9][10]
Chemistry
[edit]Chemical engineering
[edit]The use of sitosterol as a chemical intermediate was for many years limited due to the lack of a chemical point of attack on the side-chain that would permit its removal. Extensive efforts on the part of many laboratories eventually led to the discovery of apseudomonasmicrobethat efficiently effected that transformation. Fermentation digests the entire aliphatic side-chain at carbon 17 to afford a mixture of 17-keto products includingdehydroepiandrosterone.[11]
Synthesis
[edit]Total synthesis of β-sitosterol has not been achieved. However, β-sitosterol has been synthesized from stigmasterol1,which involves a specific hydrogenation of the side-chain of stigmasterol.
The first step in the synthesis forms stigmasterol tosylate2from stigmasterol1(95% purity) using p-TsCl, DMAP, and pyridine (90% yield). The tosylate2then undergoes solvolysis as it is treated with pyridine and anhydrous MeOH to give a 5:1 ratio of i-stigmasterol methyl ether3(74% yield) to stigmasterol methyl ether4,which is subsequently removed by chromatography. The hydrogenation step of a previously proposed synthesis involved the catalyst Pd/C and the solvent ethyl acetate. However, due to isomerisation during hydrolysis, other catalysts, such as PtO2,and solvents, such as ethanol, were tested. There was little change with the use of a different catalyst. Ethanol, however, prevented isomerisation and the formation of the unidentified impurity to give compound5.The last step of the synthesis is deprotection of the β-ring double bond of5with p-TsOH, aqueous dioxane, and heat (80 °C) to yield β-sitosterol6.The cumulative yield for the final two steps was 55%, and the total yield for the synthesis was 37%.[12]
Biosynthesis
[edit]
The regulation of the biosynthesis of both sterols and some specific lipids occurs during membrane biogenesis.[13]Through 13C-labeling patterns, it has been determined that both the mevalonate and deoxyxylulose pathways are involved in the formation of β-sitosterol.[14]The precise mechanism of β-sitosterol formation varies according to the organism, but is generally found to come fromcycloartenol.[15]
The biosynthesis of cycloartenol begins as one molecule ofisopentenyl diphosphate(IPP) and two molecules ofdimethylallyl diphosphate(DMAPP) formfarnesyl diphosphate(FPP). Two molecules of FPP are then joined tail-to-tail to yieldsqualene,atriterpene.Squalene, through a cyclization reaction with 2,3-oxidosqualene 6 as an intermediate forms cycloartenol.
The double bond of cycloartenol (compound 7 in diagram) is methylated by SAM to give a carbocation that undergoes a hydride shift and loses a proton to yield a compound with a methylene side-chain. Both of these steps are catalyzed by sterol C-24 methyltransferase (Step E1 in diagram). Compound 8 is then catalyzed by sterol C-4 demethylase (E2) and loses a methyl group to produce cycloeucalenol. Subsequent to this, the cyclopropane ring is opened with cycloeucalenol cycloisomerase (E3) to form10.Compound10loses a methyl group and undergoes an allylic isomerization to form gramisterol11.This step is catalyzed by sterol C-14 demethylase (E4), sterol Δ14-reductase (E5), and sterol Δ8-Δ7-isomerase (E6). The last methyl group is removed by sterol demethylase (E7) to form episterol12.Episterol12is methylated by SAM to produce a second carbocation, which loses a proton to yield13.This step is catalyzed by 24-methylenesterol C-methyltransferase (E8). Compound13now undergoes reduction by NADPH and modifications in the β-ring to form β-sitosterol. An alternative pathway is described for phytosterol synthesis in some animals, a key enzyme responsible is the sterolmethyltransferase (SMT).[3]
See also
[edit]- Charantin,a β-sitosteryl glucoside found in thebitter melonplant.
References
[edit]- ^Oja, Vahur; Chen, Xu; Hajaligol, Mohammad R.; Chan, W. Geoffrey (2009). "Sublimation Thermodynamic Parameters for Cholesterol, Ergosterol, β-Sitosterol, and Stigmasterol".Journal of Chemical & Engineering Data.54(3): 730–734.doi:10.1021/je800395m.
- ^"Nutrition data: Foods highest in beta-sitosterol per 200 calorie serving".Conde Nast, USDA National Nutrient Database, version SR-21. 2014.Archivedfrom the original on 26 September 2015.Retrieved25 September2015.
- ^abMichellod, Dolma; Bien, Tanja; Birgel, Daniel; Violette, Marlene; Kleiner, Manuel; Fearn, Sarah; Zeidler, Caroline; Gruber-Vodicka, Harald R.; Dubilier, Nicole; Liebeke, Manuel (5 May 2023)."De novo phytosterol synthesis in animals".Science.380(6644): 520–526.Bibcode:2023Sci...380..520M.doi:10.1126/science.add7830.ISSN0036-8075.PMC11139496.PMID37141360.S2CID248367784.Archivedfrom the original on 6 May 2023.Retrieved6 May2023.
- ^Wilt, T; Ishani, A; MacDonald, R; Stark, G; Mulrow, C; Lau, J (2000)."Beta-sitosterols for benign prostatic hyperplasia".The Cochrane Database of Systematic Reviews.2011(2): CD001043.doi:10.1002/14651858.CD001043.PMC8407049.PMID10796740.
- ^Kim, T. H.; Lim, H. J.; Kim, M. S.; Lee, M. S. (2012). "Dietary supplements for benign prostatic hyperplasia: An overview of systematic reviews".Maturitas.73(3): 180–5.doi:10.1016/j.maturitas.2012.07.007.PMID22883375.
- ^Rudkowska I, AbuMweis SS, Nicolle C, Jones PJ (2008). "Cholesterol-lowering efficacy of plant sterols in low-fat yogurt consumed as a snack or with a meal".J Am Coll Nutr.27(5): 588–95.doi:10.1080/07315724.2008.10719742.PMID18845709.S2CID25733066.
- ^Patel Manoj D.; Thompson Paul D. (2006). "Phytosterols and Vascular Disease".Atherosclerosis.186(1): 12–19.doi:10.1016/j.atherosclerosis.2005.10.026.PMID16325823.
- ^G. Gallina; G. Ferretti; R. Merlanti; C. Civitareale; F. Capolongo; R. Draisci; C. Montesissa (2007). "Boldenone, Boldione, and Milk Replacers in the Diet of Veal Calves: The Effects of Phytosterol Content on the Urinary Excretion of Boldenone Metabolites".J. Agric. Food Chem.55(20): 8275–8283.doi:10.1021/jf071097c.PMID17844992.
- ^Ros MM, Sterk SS, Verhagen H, Stalenhoef AF, de Jong N (2007)."Phytosterol consumption and the anabolic steroid boldenone in humans: a hypothesis piloted"(PDF).Food Addit. Contam.24(7): 679–84.doi:10.1080/02652030701216727.PMID17613052.S2CID38614535.Archived(PDF)from the original on 2020-10-03.Retrieved2019-07-06.
- ^R. Draisci; R. Merlanti; G. Ferretti; L. Fantozzi; C. Ferranti; F. Capolongo; S. Segato; C. Montesissa (2007). "Excretion profile of boldenone in urine of veal calves fed two different milk replacers".Analytica Chimica Acta.586(1–2): 171–176.Bibcode:2007AcAC..586..171D.doi:10.1016/j.aca.2007.01.026.PMID17386709.
- ^Lenz, G. R.; Kirk-Othmer Encyclopedia of Chemical Technology, 3rd ed., Wiley Interscience, London, 1983, Vol. 21, 645.
- ^McCarthy, FO; Chopra, J; Ford, A; Hogan, SA; Kerry, JP; O'Brien, NM; Ryan, E; Maguire, AR (2005). "Synthesis, isolation and characterisation of beta-sitosterol and beta-sitosterol oxide derivatives".Organic & Biomolecular Chemistry.3(16): 3059–65.doi:10.1039/b505069c.PMID16186940.
- ^Hartmann, Marie-Andrée (2003). "5 Sterol metabolism and functions in higher plants".Lipid Metabolism and Membrane Biogenesis.Topics in Current Genetics. Vol. 6. pp. 183–211.doi:10.1007/978-3-540-40999-1_6.ISBN978-3-540-20752-8.
- ^De-Eknamkul W.; Potduang B. (2003). "Biosynthesis of β-Sitosterol and Stigmasterol in Croton sublyratus Proceeds Via a Mixed Origin of Isoprene Units".Phytochemistry.62(3): 389–398.Bibcode:2003PChem..62..389D.doi:10.1016/S0031-9422(02)00555-1.PMID12620352.
- ^Dewick, P. M. Medicinal Natural Products: A Biosynthetic Approach. 3 ed.; John Wiley & Sons Ltd.: United Kingdom cyclization, 2009; p 539.