481-06-1

Basic information

• Product Name: SANTONIN
• Synonyms: SANTONIN;SANTONIN, A-;(-)-Santonine;[3S-(3alpha,3aalpha,5abeta,9bbeta)]-3a,5,5a,9b-Tetrahydro-3,5a,9-trimethylnaphtho[1,2-b]furan-2,8(3H,4H)dione;1,2,3,4,4a,7-Hexahydro-1-hydroxy-alpha, 4a,8-trimethyl-7-oxo-2-naphthaleneacetic acid gamma-lactone;11-Epiisoeusantona-1,4-dienic acid, 6alpha-hydroxy-3-oxo-, gamma-lactone;2-b)puran-2,8(3h,4h)-dione,3a,5,5a,9b-tetrahydro-3,5a,9-trimethyl-naphtho(;2-b]furan-2,8(3h,4h)-dione,3a,5,5a,9b-tetrahydro-3,5a,9-trimethyl-naphtho[
• CAS NO: 481-06-1
• Molecular Formula: C15H18O3
• Molecular Weight: 246.3
• EINECS: 207-560-7
• Product Categories: Miscellaneous Natural Products
• Mol File: 481-06-1.mol

Chemical Properties

• Melting Point: 172-173 °C(lit.)
• Boiling Point: 329.3°C (rough estimate)
• Flash Point: 189.7°C
• Appearance: /
• Density: 1.5900
• Vapor Pressure: 2.24E-07mmHg at 25°C
• Refractive Index: -172.5 ° (C=2, CHCl3)
• Storage Temp.: 2-8°C
• Solubility: Chloroform (Slightly)
• Water Solubility: 0.2g/L(17.5 oC)
• Merck: 14,8361
• BRN: 89489
• CAS DataBase Reference: SANTONIN(CAS DataBase Reference)
• NIST Chemistry Reference: SANTONIN(481-06-1)
• EPA Substance Registry System: SANTONIN(481-06-1)

Safety Data

• Hazard Codes: Xn,Xi,T+
• Statements: 22-36/37/38-26/27/28
• Safety Statements: 22-24/25-45-37-36-28-26
• RIDADR: 2811
• WGK Germany: 3
• RTECS: LE3150000
• HazardClass: 6.1(a)
• PackingGroup: II
• Hazardous Substances Data: 481-06-1(Hazardous Substances Data)

Usage

Uses

1. Anthelmintic Applications:
SANTONIN is used as an anthelmintic agent for its effectiveness in treating various parasitic worm infections.
2. Anti-pyretic Applications:
SANTONIN acts as an anti-pyretic agent, causing a decrease in temperature of mammals when tested with subjects antagonized by haloperidol.
3. Cancer Research:
(?)-α-Santonin has been used as a eudesmane-type sesquiterpene to study its effects on the impairment of 231MFP breast cancer cell survival, potentially contributing to the development of novel cancer treatments.
4. Pharmaceutical Industry:
SANTONIN is used in the pharmaceutical industry for the extraction and manufacturing of santonin, which is derived from Santonica wormseed (Artemisia cina Berg). This plant is known for its medicinal properties and is cultivated in various regions of China.
5. Chemical Research:
SANTONIN, defined as a santonin with specific substitutions at positions 3, 5a, and 9, is utilized in chemical research to study the properties and potential applications of sesquiterpene lactones.

History

The study on the chemical properties and structure of santonin was carried out at the end of the nineteenth century all the earliest research works were from the Italian scholars, such as Cannizzaro, Andreocci, Gucci, Francesconi, etc. The chemical structures determined before 1910 were all not exactly correct. Until 1929–1930, British scholars, Clemo, Haworth and Walton, finally determined the exact structure of santonin for the transformation from synthesized santonin into desmotroposanto nin and santonous acid. However, until 1940, there were no reports on structural configuration. Chinese scholars, Huang Minglong et al., basically completed the research work on the structural configuration of santonin in 1951, and the results were proved by Japanese scholars, Abe, Y. and Harukawa et al. in 1954.

Indications

As a kind of deworming drug, santonin was effective for the treatment of human roundworm infection, but it is no longer in use at present because of the development of more effective medicines.

World Health Organization (WHO)

Santonin, a crystalline lactone obtained from flowerheads of species of Artemisia, was formerly used as an anthelminthic. Its use was associated with a range of adverse effects, mainly involving the sense organs and the central nervous system, some of which were fatal. It has been superseded by other less toxic and more effective anthelminthics.

Biochem/physiol Actions

(?)-α-Santonin exhibits anti-helminthic properteis. It exhibits therapeutic effects against intestinal round worms.

Pharmacology

Santonin has a roundworm-expelling effect. It can excite worm’s ganglion which leads the worm not to be adsorbed in the intestinal wall, and then the worm is excreted out of the body after using laxatives. The effect is limited to the round worm, and it has little effect on other helminth. Excessive application can cause toxic effect. When it is excreted in urine, it can make the urine dark yellow or pink. It can be used in the treatment of ascariasis. During the medication, grease should be avoided, and laxative needs to be used such as salts. Patients with hepatosis, nephrosis and acute gastritis must contraindicate its use. The lethal dose 50 (LD50) injected under the skin of mice is 250–400 mg/kg.

Clinical Use

Santonin has been used for a long time as a kind of deworming drug. Its mechanism is between inhibitory effect on γ-GABA and excitatory effect of cholinergic func tion. It also acts on the human central nervous system and can cause some adverse effects, such as dizziness, leipopsychia, headache, epilepsy, xanthopsia, paresthesia and so onSantonin is easily dissolved and absorbed in the intestine due to alkaline intesti nal fluid and solvent effect of bile salts. Especially, it can cause severe toxic reaction more easily for increasing absorption because intake of fatty food promotes bile production, secretion and release.Santonin has obvious central nervous system toxicity. A small amount can cause colour deficiency, and a large amount can cause epileptiform, excessive excitement turning into severe repression and even coma. Santonin is a highly toxic substance. Children’s lethal dose is 0.15 g; adults’ lethal dose is about 1 g. Santonin has already been phased out for the toxicity.

InChI:InChI=1/C15H18O3/c1-8-10-4-6-15(3)7-5-11(16)9(2)12(15)13(10)18-14(8)17/h5,7-8,10,13H,4,6H2,1-3H3/t8-,10-,13+,15+/m0/s1

Upstream product

• 108-75-8 2,4,6-trimethyl-pyridine 
• 74493-65-5 (-)(11Ξ)-6α-hydroxy-11-methyl-3-oxo-eudesma-1,4-diene-12,13-dioic acid-lactone 
• 79-59-4 6-hydroxy-3-oxo-eudesma-1,4-dien-12-oic acid 
• 110-86-1 pyridine 
• 100955-42-8 (11S)-6α-hydroxy-8β-iodo-3-oxo-eudesma-1,4-dien-12-oic acid-lactone 
• 474-05-5 Pseudosantonin 
• 481-07-2 β-santonin 
• 107058-92-4 (11R)-6α-hydroxy-11-methyl-3-oxo-eudesm-4-ene-12,13-dioic acid-lactone 
• 68799-21-3 isosantonin 
• 85847-68-3 1-epi-dehydroisoerivanin 
• 98612-83-0 (6α,11β)-eudesm-2,4-dien-13,6-olide 
• 74493-65-5 (-)-11β-carboxysantonin 
• 18409-93-3 (+)-1,2-dihydro-α-santonin 
• 75683-62-4 (11S)-3-oxoeudesma-1,4(15)-dieno-12,6α-lactone 

Downstream Products

• 467-41-4 (3aS)-3c,6,6a-trimethyl-(3ar,6at,9bt)-3a,4,5,6,6a,9b-hexahydro-3H-6c,9ac-cyclo-azuleno[4,5-b]furan-2,7-dione 
• 59444-48-3 (11S)-4,5-epoxy-6α-hydroxy-3-oxo-eudesm-1-en-12-oic acid-lactone 
• 6308-44-7 3,5a,9-[trimethyl-2-oxo-2,4,5,5a,6,7-hexahydronaphtho[1,2-b]furan-8-yl] acetate 
• 14794-69-5 α-desmotroposantonin acetate 
• 14794-71-9 (-)-α-desmotroposantonin acetate 
• 571-58-4 1,4-dimethylnaphthalene 
• 79-59-4 (2R)-2-[(1S,4aS)-1-hydroxy-4a,8-dimethyl-7-oxo-1,2,3,4,4a,7-hexahydro-2-naphthalenyl]propanoic acid 
• 13902-54-0 (3S,3aS,5aS,9S,9aR,9bS)-3,5a,9-trimethyloctahydronaphtho[1,2-b]furan-2,8-dione 
• 14804-46-7 (3S,3aS,5aS,9R,9aR,9bS)-3,5a,9-trimethyloctahydronaphtho[1,2-b]furan-2,8-dione 
• 18409-93-3 (+)-1,2-dihydro-α-santonin 
• 438-50-6 8-Hydroxy-3,6,9-trimethyl-3a,4,5,9b-tetrahydro-3H-naphtho[1,2-b]furan-2-one 
• 13743-96-9 (+)-β-desmotroposantonin 
• 1618-98-0 (11S)-10α-hydroxy-30-oxoguaia-4-eno-12,6α-lactone 
• 1618-78-6 6-epi-α-Santonin 

Relevant articles and documents

Unusual Bromination of Tetrahydro-(-)-α-santonins and New Santonin Isomers: X-Ray Crystal and Molecular Structure of 2β,14-Dibromo-4α,5β,6β,11βH-tetrahydrosantonin

A novel bromination-dehydrobromination reaction of tetrahydro-(-)-α-santonins is reported which has led, via the 2α,14- and 2β,14-dibromo ketones (2a,b), to two new dienone isomers of (-)-α-santonin whose structures were established by X-ray diffraction and c.d. studies of (2b).

Synthetic approach to exo-endo cross-conjugated cyclohexadienones and its application to the syntheses of dehydrobrachylaenolide, isodehydrochamaecynone, and trans-isodehydrochamaecynone

Methodology for synthesis of exo-endo cross-conjugated dienones with trans- and cis-decalin systems has been reported. Bromination of the silyl enol ether of α′-methyl α,β-unsaturated ketones with PTAB and successive dehydrobromination of the resulting α′-bromo-α′-methyl α,β-unsaturated ketones under three conditions (DBU/PhH; TBAF/THF; Li2CO3, LiBr/DMF) gave the desired exo-endo cross-conjugated dienones in good yield. This method was applied to the syntheses of dehydrobrachylaenolide (1), isodehydro-chamaecynone (5c), and trans-isodehydrochamaecynone (11) starting from tuberiferine (7), chamaecynone (5a), and trans-chamaecynone (9). Eudesmanolides possessing an α-methylene γ-lactone moiety, i.e., 1, 7, and 13, exhibited significant inhibitory activity toward the induction of the intercellular adhesion molecule-1 (ICAM-1). Compound 1 showed greater activity than 7 and 13. All compounds possessing an ethynyl group, 5d, 9, 11, and 14, showed the same degree of termiticidal activity, and the exo-endo cross-conjugated dienone structure in 11 had no influence on the activity.

Synthesis of elemane bis-lactones from santonin - Synthesis of the reported structure of seco-isoerivanin pseudo acid and formal synthesis of (+)-8-deoxyvernolepin

The synthesis of the reported structure for seco-isoerivanin pseudo acid (1) and of an elemane bis-lactone 5 from santonin (4) through a common vinylic precursor 12 is described. Compound 5 is a known intermediate in a previous synthesis of the antitumor compound (+)-8-deoxyvernolepin (3). The vinyl group of 12 underwent a regio- and diastereoselective anti addition of an external electrophile and an intramolecular condensation to yield either the selenolactone 13 or the hydroxylactone 17. The lactones 13 and 17 served as key intermediates in the total synthesis of 1 and 5 respectively. A revision of the structure of seco-isoerivanin pseudo acid to the C-10 epimer is suggested on the basis of comparison between the spectral data of the natural and synthetic products.

A short-step synthesis of sesquiterpene lactone, 1-oxoeudesma-2,4-dien-11βh-12, 6α-olide, isolated from artemisia herba-alba and its derivatives

1-Oxoeudesma-2,4-dien-11βH-12,6α-olide(1) isolated from the genus Artemisia herb-alba was synthesized from α-santonin in a two-step sequence. The key step is the 1,3 oxidative rearrangement of dienol 7.

A formal synthesis of l-α-santonin from chiral α,β-epoxyeudesmanolide via enzyme-catalyzed hydrolysis

(4S,5R)-Epoxy-(3S)-hydroxy-(10S)-7α,11βH-eudesman-6α,12-olide 4 and (4R,5S)-epoxy-(3S)-hydroxy-(10R)-7β,11αH-eudesman-6β,12-olide 5 were obtained from (±)-3 using yeast and (3S)-acetoxy-(4S,5R)-epoxy-(10S)- 7α,11βH-eudesman-6α,12-olide 8 was produced from (±)-8 using lipase, respectively. New total synthesis of l-α-santonin (9), and its Δ(4(14))- isomers (10 and 11) were accomplished by a short step synthesis using the optically active key intermediate (10S)-8 (prepared by asymmetric hydrolysis of (±)-8).

Synthetic Transformation of Santonin into (5α,7α,11β)-3,6-Dioxogermacr-1-en-13,7-olide, a New Intermediate for Germacranes and Guaianes

A seven-step synthesis of a new intermediate (5α,7α,11β)-3,6-dioxogermacr-1-en-13,7-olide (10) is described starting from (-)-α-santonin (1).The key step in the transformation was photolytic skeletal rearrangement of (4α,5β,6α,11β)-5-hydroxy-2-oxoeudesman-13,6-olide (9) to the title compound, sensitised by mercuric oxide and iodine.

The chemistry of thujone. XI. Thujone as a chiral synthon for the preparation of sesquiterpene lactones. Synthesis of (l)-α-santonin

An efficient synthesis of (l)-α-santonin is described.The thujone-derived trienone 1, bearing only one chiral center, is transformed, via a controlled hydroboration process, to the isomeric triols 7 and 9 in which four new chiral centers (C-3, C-6, C-7, and C-11) are established in one step and with the correct absolute configuration.An oxidative cyclization process converts 7 and 9 into 1,2-dihydro-6α-santonin (3), with the latter being transformed directly to the natural product employing DDQ as a dehydrogenating agent.The overall strategy reveals an attractive synthetic entry into the family of natural sesquiterpene lactones.

Stereochemistry of Microbial Hydrogenation of (-)-α-Santonin to (+)-1,2-Dihydro-α-santonin by Streptomyces cinereocrocatus NRRL 3443

The stereochemistry of microbial transformation of (-)-α-santonin (1) by Streptomyces cinereocrocatus is described.Fermentation of (-)-α-santonin (1) with S. cinereocrocatus led to the formation of (+)-1,2-dihydro-α-santonin (2).To elucidate the stereochemistry of the microbial hydrogenation of (-)-α-santonin, (-)-2H>-α-santonin (1a) was synthesized from 1, and subjected to the microbial transformation.Analysis of the 400 MHz proton nuclear magnetic resonance spectrum of the deuterated product clearly revealed that the microbial hydrogenation of 1a proceeds stereo-specifically with trans-addition of hydrogens via si face attacks at the 1 and 2 positions. Keywords - microbial transformation; Streptomyces cinereocrocatus; (-)-α-santonin; deuterated (-)-α-santonin; (+)-1,2-dihydro-α-santonin; stereochemistry; si face attack

THE TOTAL SYNTHESIS OF 1-OXYGENATED EUDESMANOLIDES

A route towards 1-oxygenated eudesmanolides, via a (2+2) photocycloaddition reaction for constructing the decalin framework is described.The following natural substances have been synthesized. (+/-)-dihydroreynosin (1), (+/-)-1-oxo-dihydromagnolialide (2)

Biogenetic-type Synthesis of Santonin, Chrysanolide, Dihydrochrysanolide, Tulirinol, Arbusculin-C, Tanacetin, and Artemin

The title compounds were synthsised from their possible biogenetic precursors through hydroperoxide intermediates generated by photo-oxygenation.This route for biological oxygenation may serve as a substitute to epoxidation.The 13C n.m.r. special assignments for all intermediates were made.Single-crystal X-ray analyses unequivocally established the 1S configuration in dihydrochrysanolide (14) and its hydroperoxy-analogue (12).Isomorphous crystals of (12) and (14) belong to the monoclinic system, space group P21, with a = 14.350(6), b = 5.882(3), c = 10.343(3) Angstroem, β = 107.64(2) deg, Z = 2, for (12), and a = 14.461(6), b = 5.887(3), c = 9.698(4) Angstroem, β = 107.44(2) deg, Z = 2, for (14).Least-squares refinement of atomic parameters converged to R 0.040 for (12) and 0.033 for (14) over 1484 and 1300 reflections, respectively, measured by diffractometer.