Diosgenin

from Wikipedia, the free encyclopedia
Structural formula
Structural formula of diosgenin
General
Surname Diosgenin
other names

(20 R , 25 R ) -spirost-5-en-3 β -ol ( IUPAC )

Molecular formula C 27 H 42 O 3
Brief description

white to light yellow crystalline solid

External identifiers / databases
CAS number 512-04-9
EC number 208-134-3
ECHA InfoCard 100.007.396
PubChem 99474
ChemSpider 89870
Wikidata Q1107734
properties
Molar mass 414.6 g mol −1
Physical state

firmly

density

1.18 g cm −3 (at 120 K)

Melting point

200-205 ° C

solubility

Ethyl acetate > propyl acetate > ( acetone , i - propanol and ethanol )

safety instructions
GHS labeling of hazardous substances
no GHS pictograms
H and P phrases H: no H-phrases
P: no P-phrases
Toxicological data
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Diosgenin is a steroid sapogenin , which is mainly used in the industrial production of steroid compounds, oral contraceptives and sex hormones . Diosgenin occurs naturally primarily in the root tubers of the yam plant ( Dioscorea ) and the seeds of fenugreek ( Trigonella foenum graecum ) and other plants. Structurally, it is the aglycon of dioscine.

Occurrence

Fenugreek, young plants

Diosgenin occurs naturally in the tubers of many Dioscorea species ( yams ), also in fenugreek ( Trigonella foenum graecum ), Jericho tomato ( Solanum incanum ), Thai eggplant ( Solanum xanthocarpum ), vegetable asparagus ( Asparagus officinalis ) and white onion ( Allium) cepa ).

Dioscorea species:

  • D. villosa
  • D. zingiberensis
  • D. opposita
  • D. alata
  • D. japonica
  • D. deltoidea

history

After Tadeusz Reichstein and two other scientists received the Nobel Prize for Physiology / Medicine for the isolation and structural elucidation of cortisone in 1951 , several companies around the world invested in cortisone research. While Lewis H. Sarret of Merck & Company in Rahway , New Jersey , synthesized cortisone from bovine bile using 36 synthesis steps , Syntex , founded in 1944, began research into the synthesis of cortisone from diosgenin. The significantly cheaper synthesis from the diosgenin-containing yam instead of animal waste products caused cortisone prices to fall on the world market and made Syntex the world's largest manufacturer of diosgenin. In the late 1930s and early 1940s, employee Russell E. Marker succeeded in synthesizing progesterone from diosgenin. George Rosenkranz expanded the success of his colleague a short time later by synthesizing testosterone from diosgenin in addition to progesterone . A few years later, George Rosenkranz, together with Luis E. Miramontes and Carl Djerassi, obtained the progestogen norethisterone , which was also effective after oral administration and was therefore a possible contraceptive . The birth of the birth control pill was thus given.

synthesis

Diosgenin can be synthesized from the sterol cholesterol . An intermediate product is furostanol I (furost-5-en-3 β , 22,26-triol-3 β -chacotrioside-26 β - D -glucopyranoside). This sapogenin can be completely converted in plants to the diosgene glycoside, dioscin, from which the aglycon diosgenin can finally be obtained.

The figure shows a possibility of synthesizing diosgenin from cholesterol.

use

Synthesis of steroid hormones

Cortisone

The chemist Russell Marker developed a synthesis of cortisone from diosgenin. Starting from diosgenin initially the Δ7,9 (11) diene is formed, and this then in the 3 β -hydroxy-5 α -pregnane-11,20-dione converted (Route 2). From this it goes over several stages to cortisone. Another synthesis route for cortisone from diosgenin is via progesterone (route 1). Diosgenin is converted to cortisone via progesterone and 11α-hydroxyprogesterone.

The figure shows two different synthetic pathways for cortisone starting from diosgenin.

Synthesis of diosgenin derivatives

By modifying the spiroketal ring , diosgenin analogues can be synthesized. Synthesis examples are acetates , alcohols , aldehydes and ketones of diosgenin. The diosgenin analogues have gained importance, especially in medical research. One focus is the production of diosgenin analogues that have similar or better, positive properties than diosgenin. For example, ( E ) -26- (3 ', 4', 5'-trimethoxybenzylidene) -furost-5-en-3 β- acetate inhibits inflammatory cytokines .

Pharmacological effect

Diosgenin has a wide range of pharmacological effects.

Effect against microorganisms and viruses

The antimicrobial effect of Diosgenin could be confirmed in an experiment with human pathogenic yeast . On the basis of the minimum inhibitory concentrations (MIC), a slight antimicrobial effect was found against Candida albicans and Candida glabrata , whereas there was no effect against Candida tropicalis .

Effective inhibition of the replication of subgenomic HCV - replicon system's on mRNA and protein levels could be proven. The signal transmission was blocked.

Effect against cancer

In animal experiments in rats an inhibition of the cell growth of colon cancer cells and apoptosis after oral administration of diosgene could be observed. Within the study, the rats were treated with azoxymethane prior to administration of diosgene .

Other effects

In animal experiments, diosgenin showed reduced thrombosis in rats . A thrombosis caused by vena cava ligation in vitro and in vivo was examined in the rats . A dose-dependent increase in activated partial thromboplastin time (aPTT), thromboplastin time (PT) and thrombin time (TT) was observed. In mice, diosgenin was also found to reduce platelet aggregation and inhibit thrombosis in pulmonary embolism . A protracted bleeding and clotting time could be associated with an increased protection rate.

In a study, diosgenin showed clear inhibitory effects on acetylcholinesterase . This acts on neuromuscular synapses, e.g. B. in the vegetative nervous system and on the motor endplate .

In animal experiments with female rats, administration of diosgenin was able to reduce bone loss after removal of the ovaries . Other organs were not endangered.

With stimulated growth of the breast tissue epithelium over 15 days, diosgenin led to a significant increase in the DNA content and the number of milk ducts. A complementary therapy of estrogen with diosgenin increased the effect of estrogen, especially with higher doses of diosgenin.

The influence of diosgenin on the inflammatory system was examined using a co-culture of 3T3-L1 fat cells and RAW 264 macrophages . These co-cultures showed increased levels of inflammatory substances that were inhibited by diosgenin.

In rats fed a diet rich in cholesterol and fat for six weeks , the administration of diosgenin increased the activity of lipoprotein lipase (LPL), hepatic triglyceride lipase (HTGL), superoxide dismutase (SOD), and glutathione peroxidase (GPX) ) and nitric oxide synthase (NOS). The content of free oxygen radicals was reduced and the malondialdehyde (MDA), total cholesterol, triacylglyceride and LDL cholesterol levels were lowered.

Analytics

Enrichment from plants

After degreasing, the glycoside dioscin is extracted with polar solvents (e.g. ethanol ) at the boil or under reflux. The hydrolysis of the glycosidic bond takes place through acids, spontaneous fermentation or enzymatically. The released diosgenin can be extracted with a non-polar solvent and determined qualitatively and quantitatively by analytical methods. In addition to the isolation of diosgenin from natural Dioscorea types, and hydrolysis of the glycoside with inorganic acids as well as efficient and gentle isolation using ionic liquids (was ionic liquids , IL) described. With ionic liquids such as 1-methyl-3- (3-sulfopropyl) -imidazolium hydrogen sulfate ([PSMIM] HSO 4 ) it was not only possible to isolate dioscine from the sample to be examined, but the ionic liquid also served as a catalyst for the release of diosgenin Dioscin.

Analytical methods

Various methods have been developed for the identification and quantitative determination of diosgenin in Dioscorea species:

Individual evidence

  1. ↑ a b Entry on Diosgenin at ChemicalBook , accessed on May 24, 2016.
  2. ↑ Oscar E. Piro, Eduardo E. Castellano, Gloria E. Tobón Zapata, Silvia Blair Trujillo, Enrique J. Baran: Low Temperature Crystal Structure of Natural Diosgenone. In: Journal of Nature Research C . 57, 2002, pp. 947-950 ( PDF , free full text).
  3. ↑ F.-X. Chen, M.-T. Zhao, B.-Z. Ren, C.-R. Zhou and F.-F. Peng: Solubility of diosgenin in different solvents. In: The Journal of Chemical Thermodynamics. Volume 47, 2012, pp. 341-346.
  4. ↑ a b Data sheet diosgenin, ≥93% from Sigma-Aldrich , accessed on April 5, 2015 ( PDF ).
  5. ↑ a b MPbio: Safety data sheet diosgenin . Retrieved April 4, 2015.
  6. ↑ a b c C. Djerassi: Steroid research at Syntex “the pill” and cortisone In: Steroids. Vol. 57, 1992, pp. 631-641.
  7. ↑ a b c d e f g K. Patel, M. Gadewar, V. Tahilyani and DK Patel: '' A review on pharmacological and analytical aspects of diosgenin: a concise report '' In: '' Nat. Prod. Bioprospect. "Vol. 2, 2012, pp. 46-52.
  8. ↑ B. Avula, Y.-H. Wang, Z. Ali, TJ Smillie and IA Khan: Chemical fingerprint analysis and quantitative determination of steroidal compounds from Dioscorea villosa, Dioscorea species and dietary supplements using UHPLC-ELSD In: Biomedical Chromatography . Vol. 28, 2014, pp. 281-294.
  9. ↑ P. Li, Y. Mou, S. Lu, W. Sun, J. Lou, C. Yin and L. Zhou: Quantitative determination of diosgenin in Dioscorea zingiberensis cell cultures by microplate-spectrophotometry and high-performance liquid chromatography In: African Journal of Pharmacy and Pharmacology. Vol. 6 (15), 2012, pp. 1186-1193.
  10. ↑ a b c T. Yi, L.-L. Fan, H.-L. Chen, G.-Y. Zhu, H.-M. Suen, Y.-N. Tang, L. Zhu, C. Chu, Z.-Z. Zhao, H.-B. Chen: Comparative analysis of diosgenin in Dioscorea species and related medicinal plants by UPLC-DAD-MS In: BMC Biochemistry. Vol. 15, 2014, pp. 19-24.
  11. ↑ a b B. Tal, I. Tamir, SJ Rokem and I. Goldberg: Isolation and characterization of an intermediate steroid metabolite in diosgenin biosynthesis in suspension cultures of Dioscorea deltoidea cells In: Biochemical Journal . Vol. 219, 1984, pp. 619-624.
  12. ↑ a b P. Präve, U. Faust, W. Sittig and D. Sukatsch: Handbuch der Biotechnologie. Oldenbourg, 4th edition, Munich 1994, ISBN 3-486-26223-8 .
  13. ↑ M. Singh, A. Hamid, AK Maurya, O. Prakash, F. Khan, A. Kumar, O. Aiyelaagbe, AS Negi and DU Bawankule: Synthesis of diosgenin analogues as potential anti-inflammatory agents. In: Journal of Steroid Biochemistry and Molecular Biology. Vol. 143, 2014, pp. 323-333.
  14. ↑ M. Sautour, A.-C. Mitaine-Offer, T. Miyamoto, A. Dongmo and M.-A. Lacaille-Dubois: Antifungal Steroid Saponins from Dioscorea cayenensis. In: Planta Medica . Vol. 70, 2004, pp. 90-92.
  15. ↑ UA Ashfaq and S. Idress: Medicinal plants against hepatitis C virus. In: World Journal of Gastroenterology . Vol. 20, 2014, pp. 2941-2946.
  16. ↑ J. Raju, JM Patlolla, V. Swamy and CV Rao: Diosgenin, a Steroid Saponin of Trigonella foenum graecum (Fenugreek), Inhibits Azoxymethane-Induced Aberrant Crypt Foci Formation in F344 Rats and Induces Apoptosis in HT-29 Human Colon Cancer Cells . In: Cancer Epidemiology, Biomarkers & Prevention . Vol. 13, 2004, pp. 1392-1398.
  17. ↑ Entry on acetylcholinesterase in Flexikon , a Wiki of the DocCheck company , accessed on December 2, 2014.
  18. ↑ M. de Lourdes Contreras-Pacheco, F. Santacruz-Ruvalcaba, JA Garcia-Fajardo, J. de Jesus Sanchez G., MA Ruiz L., M. Estarron-Espinosa and A. Castro-Castro: Diosgenin quantification, characterization and chemical composition in a tuber collection of Dioscorea spp. in the state of Jalisco, Mexico. In: International Journal of Food Science & Technology. Vol. 48, 2013, pp. 2111-2118.
  19. ^ W. Yan, L. Ji, S. Hang, Y. Shun: New ionic liquid-based preparative method for diosgenin from Rhizoma dioscoreae nipponicae. In: Pharmacognosy Magazine. , Vol. 9 (35), 2013, pp. 250-254.
  20. ^ M Morris, B. Roark and B. Cancel: Simple precedure for the routine assay of Dioscorea tubers. In: Journal of Agricultural and Food Chemistry. Vol. 6, 1958, pp. 856-858.
  21. ↑ KR Brain and R. Hardmann: An improvement method of densitometric thin layer chromatography as applied to the determination of sapogenin in Dioscorea tubers. In: Journal of Chromatography. Vol. 38, 1968, pp. 355-363.
  22. ↑ M. Bohannon, J. Hagemann, F. Earle and A. Barclay: Screening seed of Trigonella and three related genera for diosgenin. In: Phytochemistry. Vol. 13, 1974, pp. 1513-1514.
  23. ↑ P. Brenac and Y. Sauvaire: `` Chemotaxonomic value of sterols and steroidal sapogenins in the genus Trigonella '' In: `` Ciochem. Syst. Ecol. "No. 24, 1996, pp. 157-164.
  24. ^ A b W. Taylor, M. Zaman and Z. Mir: Analysis of steroidal sapogenins from Amber fenugreek (Trigonella foenum-graecum) by capillary gas chromatography and combined gas chromatography. In: Journal of Agricultural and Food Chemistry. Vol. 45, 1997, pp. 753-759.
  25. ↑ G. Sanchez, J. Acevedo, and R. Soto: Spectrophotometric determination of diosgenin in Dioscorea composita following thin-layer-chromatography. In: Analyst. Vol. 97, 1972, pp. 973-976.
  26. ↑ H.-G. Chen, F.-Y. Jin, C. Zhao, X. Zhou, and X.-J. Gong: Content determination of total saponins in Triganelle joenumgraecum L. Chin. In: Chinese Journal of Spectroscopy Laboratory. Vol. 27, 2010, pp. 580-582.
  27. ^ G. Blunden, R. Hardman and V. Morrison: Quantitative estimation of diosgenin in tubers by densitometric thin-layer chromatography. In: J. Pharm. Sci. Vol. 56, 1967, pp. 948-955.
  28. ↑ NA Provorov, Y. Soskov, L. Lutová, O. Sokolova and S. Bairamov: Investigation of the fenugreek (Trigonella foenum-graecum L.) genotypes for fresh weight, seed productivity, symbiotic activity, callus formation and accumulation of steroids. In: Euphytica. Vol. 88, 1996, pp. 120-138.
  29. ↑ A. Ortuno, R. Oncina, J. Botia and J. Del Rio: Distribution and changes of diosgenin during development of Trigonella foenum-graecum plants. Mudulation by benzylaminopruine. In: Food Chemistry. No. 63, 1998, pp. 51-54.
  30. ↑ J. Li, D. Yang, K. Yu, J. He, Y. Zhang: Determination of diosgenin content in medicinal plants with enzyme-linked immunosorbent assay In: Planta Med. Vol. 76, pp. 1915-1920.
  31. ^ R. Hardman and T. Jefferies: A combined column-chromatographic and infrared spectrophotometric determination of diosgenin and yamogenin in fenugreek seed In: Analyst Vol. 97, 1972, pp. 437-441.
  32. ↑ J. Zhu, X. Guoa, S. Fua, X. Zhang and X. Liang: Characterization of steroidal saponins in crude extracts from Dioscorea zingiberensis CH Wright by ultra-performance liquid chromatography / electrospray ionization quadrupole time-of-flight tandem mass spectrometry In: Journal of Pharmaceutical and Biomedical Analysis Vol. 53, 2010, pp. 462-474.