US2870143A - Process for conversion of steroidal sapogenins to pseudosapogenins - Google Patents
Process for conversion of steroidal sapogenins to pseudosapogenins Download PDFInfo
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- US2870143A US2870143A US710588A US71058858A US2870143A US 2870143 A US2870143 A US 2870143A US 710588 A US710588 A US 710588A US 71058858 A US71058858 A US 71058858A US 2870143 A US2870143 A US 2870143A
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- Prior art keywords
- sapogenin
- conversion
- pseudosapogenins
- pseudosapogenin
- sapogenins
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J75/00—Processes for the preparation of steroids in general
Definitions
- This invention relates to an improved process for the conversion of steroidal sapogenins to their respective pseudosapogenins, relating particularly to performing the isomeriaation reaction under milder conditions .yet with greatly improved yields.
- the isomerization of steroidal sapogenins to pseudosapogenins is a key step in the process ofc onvertiug such sapogenins to usefulsteroidal hormones.
- This isomerization is ordinarily accomplished by. heating the sapogenin with acetic anhydride at 200 C. for hours in sealed Carius tubes or in pressure autoclaves. Itlhas been reported that poor results are obtained if the reaction is conducted at temperatures below 2 Q0 C Hence, in the present state of the art the. conversion ofsteroidal sapogenins to pseudosapo-genins "requires. .s pecial equipment for performing the reaction at highpre'ssures fyet the yields of pseudosapogenins are often poor, especially for certain specific pseudosapogenins, because of the high temperatures involved.
- the isomerization reagent is also an effective acylatio-n agent.
- the first product of the process for making pseudosapogenins are the pseudosapogenin 3,26-diacetates. These diacetates are oily and are rarely isolated.
- the free pseudosapogenin is obtained in quantitative yield upon alkaline hydrolysis of the pseudosapogenin diacetate.
- the critical feature in determining the yield of pseudosapogenin recovered is the result of the isomerization reaction. Hence, in subsequent discussions we have sometimes assumed the saponific-ation step to be included and used the terms isomerizaltion and conversion of sapogenin to pseudosapogenin synonymously.
- An object of this invention is to provide an isomerization reagent which operates effectively at temperatures under 200 C. and at pressures less than about 45 p. s. i. g.
- Another object is to provide an isomeriza-tion process which requires no special high pressure equipment.
- a further object of this invention is to provide a process in which the isomerization of steroidal sapogenins is performed in consistently high yields regardless of the particular sapogenin being converted to pseudosapogenin.
- an iso-merization reagent consisting of acetic anhydride containing a small amount of acetic acid converts steroidal sapogenins to their respective pseudosapogenins in high yields at reaction temperatures as low as 160 C. At such temperatures special equip ment is not required, the reaction being carried out in ordinary stoppered glass flasks. Conducting the reaction at these temperatures also leads to markedly improved yields of pseudosapogenins, the reaction proceeding almost quantitatively.
- sapogenins are converted to their respective pseudos-apogenins 'by a process comprising heating the sapogenin in acetic anhydride containing a small amount, preferably about 0.1 to 1% volume to volume basis, of acetic acid at temperatures below 200 C., preferably at about 170-180 C., until the isomerization is substantially complete, hydrolyzing the resulting pseudosapogenin diacetate to pseudosapogenin, and recovering the pseudosapogenin.
- the quantity of acetic acid added to the acetic anhydride can also be varied to give concentrations lower than and substantially higher than the preferred concentration of about 0:1 to 1% by volume Without aifec'ting significantly the improvement of the present invention.
- acetic anhydride-acetic acid reagent is eiiective in converting sapogenins to pseudosapogenins over a temperature range of to 200 C., temperatures of about to 180 C. are preferred. At these temperaturcs the reactions can be performed in stoppered glass flasks, the rate of yields of pseudosapogenin are high.
- EXAMPLE 3 Conversion of diosgenin to pseudodiosgenin
- the procedure of Example 1 was followed. Isomerization in acetic anhydride containing 0.1% acetic acid was conducted at 180 C. for 10 hours. From 10 grams of diosgenin there was obtained 9.0 grams of pseudodiosgenin, M. P. 157-167 C.
- EXAMPLE 4 Conversion of tigogenin to pseudotigogenin Tigogenin, 10.0 grams, was heated at 160 C. for hours in 25 ml. acetic anhydride containing 0.1% acetic acid. Following the procedures of Example 1, 7.8 grams of pseudotigogenin, M. P. 170-180 C., was recovered.
- EXAMPLE 5 7 Conversion of hecogem'n to pseudohecogenin Using the isomerization conditions of Example 4, from 10.0 grams of hecogenin there was recovered 9.1 grams of pseudohecogenin, M. P. 189-195 C.
- a process for converting a steroidal sapogenin to its psendosapogenin comprising heating said sapogenin in acetic anhydride containing about 0.1 to 1.0% by volume of acetic acid, at temperatures in the range of about to C., until the isomcrization of the sapogenin to its pseudo form is substantially complete.
Description
United States arm PROCESS FOR CONVERSION OF STEROIDAL SAPOGENINS TO PSEUDOSAPOGENINS Monroe E. Wall, Oreland, andSamuel Serota, Philadelphia, Pa assignors to the United States of America .as representedby the Secretary ofAgriculture No Drawing. Application Janpary QZ, 1958 Serial No. 710,588
Anon-exclusive, irrevocableroyalty-free license in the invention herein described, throughout the world forall purposes oi the United States Government,.with the power to grant sublicenses for such purposes, is hereby granted to .the Government of the United States of America.
This invention relates to an improved process for the conversion of steroidal sapogenins to their respective pseudosapogenins, relating particularly to performing the isomeriaation reaction under milder conditions .yet with greatly improved yields. j
The isomerization of steroidal sapogenins to pseudosapogenins is a key step in the process ofc onvertiug such sapogenins to usefulsteroidal hormones. This isomerization is ordinarily accomplished by. heating the sapogenin with acetic anhydride at 200 C. for hours in sealed Carius tubes or in pressure autoclaves. Itlhas been reported that poor results are obtained if the reaction is conducted at temperatures below 2 Q0 C Hence, in the present state of the art the. conversion ofsteroidal sapogenins to pseudosapo-genins "requires. .s pecial equipment for performing the reaction at highpre'ssures fyet the yields of pseudosapogenins are often poor, especially for certain specific pseudosapogenins, because of the high temperatures involved.
The isomerization reagent is also an effective acylatio-n agent. In actual practice the first product of the process for making pseudosapogenins are the pseudosapogenin 3,26-diacetates. These diacetates are oily and are rarely isolated. The free pseudosapogenin is obtained in quantitative yield upon alkaline hydrolysis of the pseudosapogenin diacetate. The critical feature in determining the yield of pseudosapogenin recovered is the result of the isomerization reaction. Hence, in subsequent discussions we have sometimes assumed the saponific-ation step to be included and used the terms isomerizaltion and conversion of sapogenin to pseudosapogenin synonymously.
An object of this invention is to provide an isomerization reagent which operates effectively at temperatures under 200 C. and at pressures less than about 45 p. s. i. g.
Another object is to provide an isomeriza-tion process which requires no special high pressure equipment.
A further object of this invention is to provide a process in which the isomerization of steroidal sapogenins is performed in consistently high yields regardless of the particular sapogenin being converted to pseudosapogenin.
We have discovered that an iso-merization reagent consisting of acetic anhydride containing a small amount of acetic acid converts steroidal sapogenins to their respective pseudosapogenins in high yields at reaction temperatures as low as 160 C. At such temperatures special equip ment is not required, the reaction being carried out in ordinary stoppered glass flasks. Conducting the reaction at these temperatures also leads to markedly improved yields of pseudosapogenins, the reaction proceeding almost quantitatively.
Even more surprisingly, we have found that the rate of conversion of individual steroidal sapogenins to their corresponding pseudosapogenin is markedly affected by yields .of the pseudosapogenins.
isolsapogenins, the normal isomer. is
r. 2,870,143 r Patented J an. 20, 1.959
2 the structure .of the parent .sapogenin and that heating beyond the point of complete conversion gives lower In particular, dilferences in the .spiroketal side chain configuration of sapogenins isgone factorwhich-leads to significant diiferences in the rate of conversion of the sapogenin to pseudosapogenin. In the accomp nying table (Table I) each pair of sapogenins is identical except for isomerism in the spiroketalside chain. The site of isomerism, now considered to be at C (cf. M. E. WallfExperientia 11, 340 (195.5), for areview of. pertinent literature), is.;immaterial to the presentinvention. The significance of the data in Table .I is that ineach pair of normal and converted to its respective pseudosapogenin muchmore rapidly than is the iso analogue.
TABLE L-OONVERSION 011 NATURAL SAPOGENINS 'IO PSEUDOSAPOGENINS VVITH AGETIC ANHYDRIDE-ACET- IO ACID AT 170 Sapogenin Side Chain A/B Ring Conversion isomerism Fusion Iimc, hrs.
Sarsasapogeninu NormaL..- -2 Smilagenin Iso 6 Ne0tigogenin. Normal .5 Tigogenin o 21 Yamogenin Normal A 7 Diosgenin Iso 22 :6 can alsojlalfect therate of I "to '-pseudosapogenin. The data of Table -I illustratet lI is l Nomenclature consistent with that given in Natural Products Relatedto Phenanthrenefl; 3rd ed,Eieserand Fi s rmt 5 7 1 Time req'uired for about or more of isomerization.
. 2 We havekalso foundthat 'diflerences inconfiguration at conversion 7 ofsapogenin influenceiis in thelorderof C cis C trans 'CA According to the present invention sapogenins are converted to their respective pseudos-apogenins 'by a process comprising heating the sapogenin in acetic anhydride containing a small amount, preferably about 0.1 to 1% volume to volume basis, of acetic acid at temperatures below 200 C., preferably at about 170-180 C., until the isomerization is substantially complete, hydrolyzing the resulting pseudosapogenin diacetate to pseudosapogenin, and recovering the pseudosapogenin.
Although we usually use a ratio of 2.5 parts of acetic anhydride containing acetic acid to one part of sapogenin, this ratio is not critical to the practice of the invention. Both higher and lower ratios of acetic anhydride-acetic acid to sapogenin have been used successfully.
The quantity of acetic acid added to the acetic anhydride can also be varied to give concentrations lower than and substantially higher than the preferred concentration of about 0:1 to 1% by volume Without aifec'ting significantly the improvement of the present invention.
While the acetic anhydride-acetic acid reagent is eiiective in converting sapogenins to pseudosapogenins over a temperature range of to 200 C., temperatures of about to 180 C. are preferred. At these temperaturcs the reactions can be performed in stoppered glass flasks, the rate of yields of pseudosapogenin are high.
The following examples are presented in illustration of the present invention.
EXAMPLE 1 Conversion of sarsasapogenin to pseudosarsasapogenin of acetic anisomerization is satisfactory, and the.
residue saponified by refluxing in 200 ml. of methanol containing 20.0 grams of potassium hydroxide. On dilu- EXAMPLE 2 Conversion of smilagenin to pseudosmilagenin Smilagenin. 10.0 grams, was heated 6 hours at 170 C. with 25 m1. of acetic anhydride containing 0.1% acetic acid. Following the procedures described in Example 1, pseudosmilagcnin was recovered. Recrystallization from ethyl acetate gave 8.8 grams of pseudosmilagcm'n, M. P. 161-162 C.
EXAMPLE 3 Conversion of diosgenin to pseudodiosgenin In general, the procedure of Example 1 was followed. Isomerization in acetic anhydride containing 0.1% acetic acid was conducted at 180 C. for 10 hours. From 10 grams of diosgenin there was obtained 9.0 grams of pseudodiosgenin, M. P. 157-167 C.
EXAMPLE 4 Conversion of tigogenin to pseudotigogenin Tigogenin, 10.0 grams, was heated at 160 C. for hours in 25 ml. acetic anhydride containing 0.1% acetic acid. Following the procedures of Example 1, 7.8 grams of pseudotigogenin, M. P. 170-180 C., was recovered.
' 1 l-oxo-diosgenin.
EXAMPLE 5 7 Conversion of hecogem'n to pseudohecogenin Using the isomerization conditions of Example 4, from 10.0 grams of hecogenin there was recovered 9.1 grams of pseudohecogenin, M. P. 189-195 C.
EXAMPLE 6 Using procedures similar to those of preceding examples, ll-oxo-tigogenin and ll-oxo-diosgenin were converted to their pseudo analogues. Identification verified by comparison of infrared spectra with those of authentic pseudo compounds.
We claim:
1. A process for converting a steroidal sapogenin to its psendosapogenin comprising heating said sapogenin in acetic anhydride containing about 0.1 to 1.0% by volume of acetic acid, at temperatures in the range of about to C., until the isomcrization of the sapogenin to its pseudo form is substantially complete.
2. The process of claim 1 in which the sapogenin is sarsasapogenin.
3. The process of claim 1 smilagenin.
4. The process of claim 1 diosgenin.
5. The process of hecogenin.
6. The process of claim 1 tigogenin.
7. The process of claim 1 1 l-oxo-tigogenin.
8. The process of claim 1 in which the sapogenin is in which the sapogenin is claim 1 in which the sapogenin is in which the'sapogenin is in which the sapogenin is in which the sapoge nin is References Cited in the tile or this patent Marker: I. A. C. S. September 1947, pages 2170, 2184, 2191, 2194, 2196.. V
Claims (1)
1. A PROCESS FOR CONVERTING A STEROIDAL SAPOGENIN TO ITS PSEUDOSAPOGENIN COMPRISING HEATING SAID SAPOGENIN IN ACETIC ANHYDRIDE CONTAINING ABOUT 0.1 TO 1.0% BY VOLUME OF ACETIC ACID, AT TEMPERATURES IN THE RANGE OF ABOUT 160 TO 180* C., UNTIL THE ISOMERIZATION OF THE SAPOGENIN TO ITS PSEUDO FORM IS SUBSTANTIALLY COMPLETE.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US710588A US2870143A (en) | 1958-01-22 | 1958-01-22 | Process for conversion of steroidal sapogenins to pseudosapogenins |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US710588A US2870143A (en) | 1958-01-22 | 1958-01-22 | Process for conversion of steroidal sapogenins to pseudosapogenins |
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| US2870143A true US2870143A (en) | 1959-01-20 |
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| Application Number | Title | Priority Date | Filing Date |
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| US710588A Expired - Lifetime US2870143A (en) | 1958-01-22 | 1958-01-22 | Process for conversion of steroidal sapogenins to pseudosapogenins |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3005817A (en) * | 1956-04-05 | 1961-10-24 | Olin Mathieson | 12alpha-halo-delta20(22)-furostene-3beta, 26-diol-11-one 3, 26-diacylate and preparation thereof |
| US20050113316A1 (en) * | 2001-07-24 | 2005-05-26 | Panagin Pharmaceuticals Inc. | Process for producing dammarane sapogenins and ginsenosides |
-
1958
- 1958-01-22 US US710588A patent/US2870143A/en not_active Expired - Lifetime
Non-Patent Citations (1)
| Title |
|---|
| None * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3005817A (en) * | 1956-04-05 | 1961-10-24 | Olin Mathieson | 12alpha-halo-delta20(22)-furostene-3beta, 26-diol-11-one 3, 26-diacylate and preparation thereof |
| US20050113316A1 (en) * | 2001-07-24 | 2005-05-26 | Panagin Pharmaceuticals Inc. | Process for producing dammarane sapogenins and ginsenosides |
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