Sarsasapogenin
Encyclopedia
Sarsasapogenin is a steroid
al sapogenin
, that is the aglycosidic portion of a plant saponin
. It is named after sarsaparilla
(Smilax
sp.), a family of climbing plants found in subtropical regions. It was one of the first sapogenins to be identified, and the first spirostan steroid to be identified as such. 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. 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. It has also attracted pharmaceutical interest in its own right, and is found in the rhizome of Anemarrhena asphodeloides
, used in Chinese tradition medicine (知母, zhī mǔ), from which it is extracted commercially.
– with one or more sugar units attached to the hydroxyl group, known as a saponin
– in the roots of many species of monocotyledon
ous plant, in particular:
Smilacaceae
Asparagaceae
Agavaceae
The sarsasapogenin saponin can be extracted from the dried powdered root with 95% ethanol
. After removal of the fat from the resulting gum, the glycosidic linkage is hydrolyzed
with hydrochloric acid
(approx. 2 M) and the resulting crude steroid is recrystallized
from anhydrous acetone
. The yield of pure sarsasapogenin from 225 kg of Smilax root is reported to be about 450 grams.
structure based on degradation studies which indicated an ether
oxygen atom attached to C-16. The true nature of the side chain – a ketone
spiro
acetal
– was discovered by Russell Marker in 1939, when he succeeded in opening the six-membered pyran
ring with acetic anhydride
. 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 (a progesterone
analogue) and testosterone
. However, for large scale production of steroid hormones, it proved more convenient to use diosgenin
(extracted from the Mexican yam Dioscorea mexicana
) as the starting material, as it contains a double bond in the steroid nucleus.
s (mAChRs) in animal models of Alzheimer's disease
. In both cases, the effects seem to be specific to the 5β-configuration, the cis-linkage between rings A and B, as diosgenin
(with a Δ5 double bond which can be hydrogenated in the body) had much lower anti-diabetic activity (and no significant effect on mAChRs) while tigogenin (the 5α-epimer of smilagenin) showed no effect at all in either study.
Steroid
A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...
al sapogenin
Sapogenin
Sapogenins are the aglycones, or non-saccharide, portions of the family of natural products known as saponins. Sapogenins contain steroid or other triterpene frameworks as their key organic feature. For example, steroidal sapogenins like tiggenin, neogitogenin, and tokorogenin have been isolated...
, that is the aglycosidic portion of a plant saponin
Saponin
Saponins are a class of chemical compounds, one of many secondary metabolites found in natural sources, with saponins found in particular abundance in various plant species...
. It is named after sarsaparilla
Sarsaparilla
is a perennial trailing vine with prickly stems that is native to Central America. Common names include Sarsaparilla , Honduran Sarsaparilla, and Jamaican Sarsaparilla...
(Smilax
Smilax
Smilax is a genus of about 300-350 species, found in temperate zones, tropics and subtropics worldwide. In China for example about 80 are found , while there are 20 in North America north of Mexico...
sp.), a family of climbing plants found in subtropical regions. It was one of the first sapogenins to be identified, and the first spirostan steroid to be identified as such. The identification of the spirostan structure, with its ketone spiro acetal functionality, was fundamental in the development of the Marker degradation
Marker degradation
The Marker degradation is a three-step synthetic route in steroid chemistry developed by American chemist Russell Earl Marker in 1938–40. It is used for the production of cortisone and mammalian sex hormones from plant steroids, and established Mexico as a world center for steroid production in...
, which allowed the industrial production of progesterone
Progesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
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. 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. It has also attracted pharmaceutical interest in its own right, and is found in the rhizome of Anemarrhena asphodeloides
Anemarrhena asphodeloides
Anemarrhena asphodeloides is a plant species in family Asparagaceae, subfamily Agavoideae. It has also been placed in its own family, Anemarrhenaceae.The plant name in China is zhi mu and its rhizome is used in traditional medicine....
, used in Chinese tradition medicine (知母, zhī mǔ), from which it is extracted commercially.
Occurrence and isolation
Sarsasapogenin is found as a glycosideGlycoside
In chemistry, a glycoside is a molecule in which a sugar is bound to a non-carbohydrate moiety, usually a small organic molecule. Glycosides play numerous important roles in living organisms. Many plants store chemicals in the form of inactive glycosides. These can be activated by enzyme...
– with one or more sugar units attached to the hydroxyl group, known as a saponin
Saponin
Saponins are a class of chemical compounds, one of many secondary metabolites found in natural sources, with saponins found in particular abundance in various plant species...
– in the roots of many species of monocotyledon
Monocotyledon
Monocotyledons, also known as monocots, are one of two major groups of flowering plants that are traditionally recognized, the other being dicotyledons, or dicots. Monocot seedlings typically have one cotyledon , in contrast to the two cotyledons typical of dicots...
ous plant, in particular:
Smilacaceae
Smilacaceae
Smilacaceae, the greenbrier family, is a family of flowering plants. Up to some decades ago the genera now included in family Smilacaceae were often assigned to a more broadly defined family Liliaceae, but for the past twenty to thirty years most botanists have accepted Smilacaceae as a distinct...
- SmilaxSmilaxSmilax is a genus of about 300-350 species, found in temperate zones, tropics and subtropics worldwide. In China for example about 80 are found , while there are 20 in North America north of Mexico...
sp.- Smilax regelii Kilip & C. V. Morton (Honduran sarsaparilla)
- Smilax ornata Hook.f. (Jamaican sarsaparilla, synonym of S. regelii)
- Smilax aristolochiaefolia Mill. (American sarsaparilla)
- Smilax asperaSmilax asperaSmilax aspera, common name Rough Bindweed or Sarsaparille, is a species of flowering vine in the greenbriar family, Smilacaceae.-Description:...
L. (Spanish sarsaparilla) - Smilax glabra Roxb. (in Chinese, tǔfúlíng 土茯苓)
- Smilax febrifuga Kunth (Ecuadorian or Peruvian sarsaparilla)
- Smilax regelii Kilip & C. V. Morton (Honduran sarsaparilla)
Asparagaceae
Asparagaceae
Asparagaceae is the botanical name of a family of flowering plants, placed in the order Asparagales of the monocots.In earlier classification systems, the species involved were often treated as belonging to the family Liliaceae...
- AsparagusAsparagusAsparagus officinalis is a spring vegetable, a flowering perennialplant species in the genus Asparagus. It was once classified in the lily family, like its Allium cousins, onions and garlic, but the Liliaceae have been split and the onion-like plants are now in the family Amaryllidaceae and...
sp.
Agavaceae
Agavaceae
Agavoideae is a subfamily of monocot flowering plants in the family Asparagaceae, order Asparagales. It has previously been treated as a separate family, Agavaceae. The group includes many well-known desert and dry zone types such as the agave, yucca, and Joshua tree...
- Anemarrhena sp.
- Anemarrhena asphodeloidesAnemarrhena asphodeloidesAnemarrhena asphodeloides is a plant species in family Asparagaceae, subfamily Agavoideae. It has also been placed in its own family, Anemarrhenaceae.The plant name in China is zhi mu and its rhizome is used in traditional medicine....
Bunge (in Chinese, zhī mǔ 知母)
- Anemarrhena asphodeloides
- YuccaYuccaYucca is a genus of perennial shrubs and trees in the family Asparagaceae, subfamily Agavoideae. Its 40-50 species are notable for their rosettes of evergreen, tough, sword-shaped leaves and large terminal panicles of white or whitish flowers. They are native to the hot and dry parts of North...
sp.- Yucca schidigera Roezl ex Ortges (Mojave yucca)
- Yucca brevifolia Enulm. (Joshua tree)
- AgaveAgaveAgave is a genus of monocots. The plants are perennial, but each rosette flowers once and then dies ; they are commonly known as the century plant....
sp.
The sarsasapogenin saponin can be extracted from the dried powdered root with 95% ethanol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
. After removal of the fat from the resulting gum, the glycosidic linkage is hydrolyzed
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...
with hydrochloric acid
Hydrochloric acid
Hydrochloric acid is a solution of hydrogen chloride in water, that is a highly corrosive, strong mineral acid with many industrial uses. It is found naturally in gastric acid....
(approx. 2 M) and the resulting crude steroid is recrystallized
Recrystallization (chemistry)
-Chemistry:In chemistry, recrystallization is a procedure for purifying compounds. The most typical situation is that a desired "compound A" is contaminated by a small amount of "impurity B". There are various methods of purification that may be attempted , which includes recrystallization...
from anhydrous acetone
Acetone
Acetone is the organic compound with the formula 2CO, a colorless, mobile, flammable liquid, the simplest example of the ketones.Acetone is miscible with water and serves as an important solvent in its own right, typically as the solvent of choice for cleaning purposes in the laboratory...
. The yield of pure sarsasapogenin from 225 kg of Smilax root is reported to be about 450 grams.
History
Sarsasapogenin was first isolated in 1914 from Sarsaparilla root. 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 tetrahydrofuranTetrahydrofuran
Tetrahydrofuran is a colorless, water-miscible organic liquid with low viscosity at standard temperature and pressure. This heterocyclic compound has the chemical formula 4O. As one of the most polar ethers with a wide liquid range, it is a useful solvent. Its main use, however, is as a precursor...
structure based on degradation studies which indicated an ether
Ether
Ethers are a class of organic compounds that contain an ether group — an oxygen atom connected to two alkyl or aryl groups — of general formula R–O–R'. A typical example is the solvent and anesthetic diethyl ether, commonly referred to simply as "ether"...
oxygen atom attached to C-16. The true nature of the side chain – a ketone
Ketone
In organic chemistry, a ketone is an organic compound with the structure RCR', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology...
spiro
Spiro
Spiro or Spyro may refer to:* ARA Spiro , the corvette of the Argentine Navy named after Samuel Spiro, a Greek tanker in service 1974-75* Spiro Agnew, thirty-ninth Vice President of the United States* Spiro curves, i.e...
acetal
Acetal
An acetal is a molecule with two single-bonded oxygen atoms attached to the same carbon atom.Traditional usages distinguish ketals from acetals...
– was discovered by Russell Marker in 1939, when he succeeded in opening the six-membered pyran
Pyran
In chemistry, a pyran, or oxine, is a six-membered heterocyclic, non-aromatic ring, consisting of five carbon atoms and one oxygen atom and containing two double bonds. The molecular formula is C5H6O. There are two isomers of pyran that differ by the location of the double bonds...
ring with acetic anhydride
Acetic anhydride
Acetic anhydride, or ethanoic anhydride, is the chemical compound with the formula 2O. Commonly abbreviated Ac2O, it is the simplest isolatable acid anhydride and is a widely used reagent in organic synthesis...
. Marker found that almost the entire side chain could be cleaved in three steps, a process now known as the Marker degradation
Marker degradation
The Marker degradation is a three-step synthetic route in steroid chemistry developed by American chemist Russell Earl Marker in 1938–40. It is used for the production of cortisone and mammalian sex hormones from plant steroids, and established Mexico as a world center for steroid production in...
.
Marker was able to convert sarsasapogenin into pregane-3,20-diol (a progesterone
Progesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
analogue) and testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
. However, for large scale production of steroid hormones, it proved more convenient to use diosgenin
Diosgenin
Diosgenin, a steroid sapogenin, is the product of hydrolysis by acids, strong bases, or enzymes of saponins, extracted from the tubers of Dioscorea wild yam, such as the Kokoro...
(extracted from the Mexican yam Dioscorea mexicana
Dioscorea mexicana
Mexican yam or barbasco de placa is a species of yam in the genus Dioscorea. It ranges from the state of Veracruz in Mexico south to Panama. It is notable for its production of diosgenin, which is a precursor for the synthesis of hormones such as progesterone. Russell Marker developed the...
) as the starting material, as it contains a double bond in the steroid nucleus.
Pharmacological interest
Sarsasapogenin and its C-25 epimer smilagenin lowered blood sugar and reversed diabetic weight gain in experiments with in mice with a mutant diabetes gene (db). Both steroids also halted the decline in muscarinic acetylcholine receptorMuscarinic acetylcholine receptor
Muscarinic receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled in the plasma membranes of certain neurons and other cells...
s (mAChRs) in animal models of Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
. In both cases, the effects seem to be specific to the 5β-configuration, the cis-linkage between rings A and B, as diosgenin
Diosgenin
Diosgenin, a steroid sapogenin, is the product of hydrolysis by acids, strong bases, or enzymes of saponins, extracted from the tubers of Dioscorea wild yam, such as the Kokoro...
(with a Δ5 double bond which can be hydrogenated in the body) had much lower anti-diabetic activity (and no significant effect on mAChRs) while tigogenin (the 5α-epimer of smilagenin) showed no effect at all in either study.