Difference between revisions of "Sarsasapogenin"

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Sarsasapogenin has been used as a starting material for the synthesis of other steroids.<ref>{{citation | inventor1-last = Dryden, Jr. | inventor1-first = Hugh L. | inventor2-last = Markos | inventor2-first = Charles S. | assignee = Searle & Co. | title = Process for the preparation of 17β-hydroxy-3-oxo-17α-pregn-4-ene-21-carboxylic acid γ-lactone | country-code = US | patent-number = 4057543 | publication-date = 1977-11-08}}.</ref> It has also attracted pharmaceutical interest in its own right,<ref>{{citation | inventor1-last = Applezweig | inventor1-first = Norman | assignee = Progenics Inc. | title = Treatment of obesity and diabetes using sapogenins | country-code = US | patent-number = 4680289 | publication-date = 1987-07-14}}.</ref><ref>{{citation | inventor1-last = Xia | inventor1-first = Zongqin | inventor2-last = Hu | inventor2-first = Yaer | inventor3-last = Rubin | inventor3-first = Ian | inventor4-last = Brostoff | inventor4-first = Jonathan | inventor5-last = Whittle | inventor5-first = Brian | inventor6-last = Wang | inventor6-first = Weijun | inventor7-last = Gunning | inventor7-first = Phil | assignee = Phytopharm plc | title = Steroidal sapogenins and their derivatives for treating alzheimer's disease | country-code = US | patent-number = 6812213 | publication-date = 2002-12-19}}.</ref><ref>{{citation | first1 = Yaer | last1 = Hu | first2 = Zongqin | last2 = Xia | first3 = Qixiang | last3 = Sun | first4 = Antonia | last4 = Orsi | first5 = Daryl | last5 = Rees | title = A new approach to the pharmacological regulation of memory: Sarsasapogenin improves memory by elevating the low muscarinic acetylcholine receptor density in brains of memory-deficit rat models | journal = Brain Research | year = 2005 | volume = 1060 | issue = 1–2 | pages = 26–39 | doi = 10.1016/j.brainres.2005.08.019}}.</ref> and is found in the rhizome of ''Anemarrhena asphodeloides'', used in Chinese tradition medicine (知母, ''zhī mǔ''), from which it is extracted commercially.<ref name="Wilshire">{{citation | url = http://www.wilshiretechnologies.com/steroidal_saponins_and_sapogenins_pdf/sarsasapogenin.pdf | title = Sarsasapogenin | publisher = Wilshire Technologies | accessdate = 2010-03-07}}.</ref>
 
Sarsasapogenin has been used as a starting material for the synthesis of other steroids.<ref>{{citation | inventor1-last = Dryden, Jr. | inventor1-first = Hugh L. | inventor2-last = Markos | inventor2-first = Charles S. | assignee = Searle & Co. | title = Process for the preparation of 17β-hydroxy-3-oxo-17α-pregn-4-ene-21-carboxylic acid γ-lactone | country-code = US | patent-number = 4057543 | publication-date = 1977-11-08}}.</ref> It has also attracted pharmaceutical interest in its own right,<ref>{{citation | inventor1-last = Applezweig | inventor1-first = Norman | assignee = Progenics Inc. | title = Treatment of obesity and diabetes using sapogenins | country-code = US | patent-number = 4680289 | publication-date = 1987-07-14}}.</ref><ref>{{citation | inventor1-last = Xia | inventor1-first = Zongqin | inventor2-last = Hu | inventor2-first = Yaer | inventor3-last = Rubin | inventor3-first = Ian | inventor4-last = Brostoff | inventor4-first = Jonathan | inventor5-last = Whittle | inventor5-first = Brian | inventor6-last = Wang | inventor6-first = Weijun | inventor7-last = Gunning | inventor7-first = Phil | assignee = Phytopharm plc | title = Steroidal sapogenins and their derivatives for treating alzheimer's disease | country-code = US | patent-number = 6812213 | publication-date = 2002-12-19}}.</ref><ref>{{citation | first1 = Yaer | last1 = Hu | first2 = Zongqin | last2 = Xia | first3 = Qixiang | last3 = Sun | first4 = Antonia | last4 = Orsi | first5 = Daryl | last5 = Rees | title = A new approach to the pharmacological regulation of memory: Sarsasapogenin improves memory by elevating the low muscarinic acetylcholine receptor density in brains of memory-deficit rat models | journal = Brain Research | year = 2005 | volume = 1060 | issue = 1–2 | pages = 26–39 | doi = 10.1016/j.brainres.2005.08.019}}.</ref> and is found in the rhizome of ''Anemarrhena asphodeloides'', used in Chinese tradition medicine (知母, ''zhī mǔ''), from which it is extracted commercially.<ref name="Wilshire">{{citation | url = http://www.wilshiretechnologies.com/steroidal_saponins_and_sapogenins_pdf/sarsasapogenin.pdf | title = Sarsasapogenin | publisher = Wilshire Technologies | accessdate = 2010-03-07}}.</ref>
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==History==
 +
Sarsasapogenin was first isolated in 1914 from Sarsapilla root.<ref name="Power"/> Although it was known to have three oxygen atoms, of which only one is a hydroxyl group, the structure of the side chain remained unclear for many years. Tschesche and Hagedorn proposed an unreactive double [[tetrahydrofuran]] structure based on degradation studies which showed an ether oxygen atom attached to C-16.<ref>{{citation | last1 = Tschesche | last2 = Hagedorn | journal = Ber. Dtsch. Chem. Ges. | year = 1935 | volume = 68 | page = 1412}}.</ref> The true nature of the side chain – a [[ketone]] [[spiro]] [[acetal]] – was discovered by [[Russell Earl Marker|Russell Marker]] in 1939, when he succeded in opening the six-membered [[pyran]] ring with [[acetic anhydride]].<ref name="LIII"/> Marker found that almost the entire side chain could be cleaved in three steps, a process now known as the [[Marker degradation]].
 +
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Marker was able to convert sarsasapogenin into [[pregane-3,20-diol]]<ref name="LXXXI">{{citation | title = Sterols. LXXXI. Conversion of Sarsasapogenin to Pregnanediol-3(α),20(α) | first1 = Russell E. | last1 = Marker | authorlink1 = Russell Earl Marker | first2 = Ewald | last2 = Rohrmann | journal = J. Am. Chem. Soc. | year = 1939 | volume = 61 | isuue = 12 pages =  3592–93 | doi = 10.1021/ja01267a513}}. {{citation | title = Sterols. LXXXVIII. Pregnanediols from Sarsasapogenin  | first1 = Russell E. | last1 = Marker | authorlink1 = Russell Earl Marker | first2 = Ewald | last2 = Rohrmann | journal = J. Am. Chem. Soc. | year = 1940 | volume = 62 | issue = 3 | pages = 518–20 | doi = 10.1021/ja01860a017}}.</ref> (a [[progesterone]] analogue) and [[testosterone]].<ref name="CV">{{citation | title = Sterols. CV. The Preparation of Testosterone and Related Compounds from Sarsasapogenin and Diosgenin | first = Russell E. | last = Marker | authorlink = Russell Earl Marker | journal = J. Am. Chem. Soc. | year = 1940 | volume = 62 | issue = 9 | pages = 2543–47 | doi = 10.1021/ja01866a077}}.</ref>
  
 
==References==
 
==References==

Revision as of 05:42, 8 March 2010

Sarsasapogenin
Sarsasapogenin.png
IUPAC name (3β,5β,25S)-spirostan-3-ol
Identifiers
InChI InChI=1/C27H44O3/c1-16-7-12-27 (29-15-16)17(2)24-23(30-27)14- 22-20-6-5-18-13-19(28)8-10-25( 18,3)21(20)9-11-26(22,24)4/h16 -24,28H,5-15H2,1-4H3/t16-,17-, 18+,19-,20+,21-,22-,23-,24-,25 -,26-,27+/m0/s1
InChIKey GMBQZIIUCVWOCD-WWASVFFGBR
Standard InChI InChI=1S/C27H44O3/c1-16-7-12-2 7(29-15-16)17(2)24-23(30-27)14 -22-20-6-5-18-13-19(28)8-10-25 (18,3)21(20)9-11-26(22,24)4/h1 6-24,28H,5-15H2,1-4H3/t16-,17- ,18+,19-,20+,21-,22-,23-,24-,2 5-,26-,27+/m0/s1
Standard InChIKey GMBQZIIUCVWOCD-WWASVFFGSA-N
CAS number [126-19-2]
EC number 204-776-3
ChemSpider 83145
Properties[1]
Chemical formula C27H44O3
Molar mass 416.64 g/mol
Melting point

199–199.5 °C

Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)

Sarsasapogenin is a steroidal sapogenin, that is the aglycosidic portion of a plant saponin. It is named after sarsaparilla (Smilax sp.),[2] a family of climbing plants found in subtropical regions. It was one of the first sapogenins to be identified,[2] and the first spirostan steroid to be identified as such.[3] The identification of the spirostan structure, with its ketone spiro acetal functionality, was fundamental in the development of the Marker degradation, which allowed the industrial production of progesterone and other sex hormones from plant steroids.

Sarsasapogenin is unusual in that it has a cis-linkage between rings A and B of the steroid nucleus, as opposed to the more usual trans-linkage found in other saturated steroids. This 5β configuration is biologically significant, as a specific enzyme – sarsasapogenin 3β-glucosyltransferase – is found in several plants for the glycosylation of sarsasapogenin.[4] The (S)-configuration at C-25 is also in contrast to other spirostan sapogenins: the epimer with a (25R)-configuration is known as smilagenin.

Sarsasapogenin has been used as a starting material for the synthesis of other steroids.[5] It has also attracted pharmaceutical interest in its own right,[6][7][8] and is found in the rhizome of Anemarrhena asphodeloides, used in Chinese tradition medicine (知母, zhī mǔ), from which it is extracted commercially.[9]

History

Sarsasapogenin was first isolated in 1914 from Sarsapilla root.[2] Although it was known to have three oxygen atoms, of which only one is a hydroxyl group, the structure of the side chain remained unclear for many years. Tschesche and Hagedorn proposed an unreactive double tetrahydrofuran structure based on degradation studies which showed an ether oxygen atom attached to C-16.[10] The true nature of the side chain – a ketone spiro acetal – was discovered by Russell Marker in 1939, when he succeded in opening the six-membered pyran ring with acetic anhydride.[3] Marker found that almost the entire side chain could be cleaved in three steps, a process now known as the Marker degradation.

Marker was able to convert sarsasapogenin into pregane-3,20-diol[11] (a progesterone analogue) and testosterone.[12]

References

  1. ↑ Jacobs, Walter A.; Simpson, James C. E. On Sarsasapogenin and Gitogenin. J. Biol. Chem. 1934, 105 (3), 501–10, <http://www.jbc.org/content/105/3/501.full.pdf>.
  2. ↑ 2.0 2.1 2.2 Power, Frederick Belding; Salway, Arthur Henry Chemical examination of sarsaparilla root. J. Chem. Soc., Trans. 1914, 105, 201–19. DOI: 10.1039/CT9140500201.
  3. ↑ 3.0 3.1 Marker, Russell E.; Rohrmann, Ewald Sterols. LIII. The Structure of the Side Chain of Sarsasapogenin. J. Am. Chem. Soc. 1939, 61 (4), 846–51. DOI: 10.1021/ja01873a020.
  4. ↑ Paczkowski, Cezary; Wojciechowski, Zdzisław A. The occurrence of UDPG-dependent glucosyltransferase specific for sarsasapogenin in Asparagus officinalis. Phytochemistry 1988, 27 (9), 2743–47. DOI: 10.1016/0031-9422(88)80654-X.
  5. ↑ Dryden, Jr., Hugh L.; Markos, Charles S. (Searle & Co.) Process for the preparation of 17β-hydroxy-3-oxo-17α-pregn-4-ene-21-carboxylic acid γ-lactone. US Patent 4057543, published 8 November 1977.
  6. ↑ Applezweig, Norman (Progenics Inc.) Treatment of obesity and diabetes using sapogenins. US Patent 4680289, published 14 July 1987.
  7. ↑ Xia, Zongqin; Hu, Yaer; Rubin, Ian, et al. (Phytopharm plc) Steroidal sapogenins and their derivatives for treating alzheimer's disease. US Patent 6812213, published 19 December 2002.
  8. ↑ Hu, Yaer; Xia, Zongqin; Sun, Qixiang; Orsi, Antonia; Rees, Daryl A new approach to the pharmacological regulation of memory: Sarsasapogenin improves memory by elevating the low muscarinic acetylcholine receptor density in brains of memory-deficit rat models. Brain Research 2005, 1060 (1–2), 26–39. DOI: 10.1016/j.brainres.2005.08.019.
  9. ↑ Sarsasapogenin; Wilshire Technologies, <http://www.wilshiretechnologies.com/steroidal_saponins_and_sapogenins_pdf/sarsasapogenin.pdf>. (accessed 7 March 2010).
  10. ↑ Tschesche; Hagedorn Ber. Dtsch. Chem. Ges. 1935, 68, 1412.
  11. ↑ Marker, Russell E.; Rohrmann, Ewald Sterols. LXXXI. Conversion of Sarsasapogenin to Pregnanediol-3(α),20(α). J. Am. Chem. Soc. 1939, 61. DOI: 10.1021/ja01267a513. Marker, Russell E.; Rohrmann, Ewald Sterols. LXXXVIII. Pregnanediols from Sarsasapogenin. J. Am. Chem. Soc. 1940, 62 (3), 518–20. DOI: 10.1021/ja01860a017.
  12. ↑ Marker, Russell E. Sterols. CV. The Preparation of Testosterone and Related Compounds from Sarsasapogenin and Diosgenin. J. Am. Chem. Soc. 1940, 62 (9), 2543–47. DOI: 10.1021/ja01866a077.
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