Structure<unk>  was first isolated from Amanita pantherina by Onda in 1964, and thought to be an amino acid or peptide. Structure was then elucidated by Takemoto, Eugster, and Bowden.<unk>  is a semi-rigid isoxazole containing both alcohol and aminomethyl substituents.<unk>  is commonly portrayed as a tautomer, where it adopts an amide-like configuration. It is also commonly shown as a zwitterion. Isolation<unk>  can be extracted from the flesh of the Amanita muscaria by treatment with boiling water, followed by rapid cooling, and further treatment with a basic resin. This is washed with water, and eluted with acetic acid using column chromatography. The eluate is freeze dried, dissolved in water, and passed down a column of cellulose phosphate. A subsequent elution with ammonium hydroxide and recrystallization from alcohol results in pure<unk> . In instances where pure<unk>  is not required, such as recreational or spiritual use, a crude extract is often prepared by simmering dried Amanita muscaria in water for thirty minutes. Chemical Synthesis<unk>  was synthesized in 1965 by Gagneux, who utilized a bromo-isoxazole starting material in a two step reaction. 3-bromo-5-aminomethyl-isoxazole (1) was refluxed in a mixture of Methanol and Potassium Hydroxide for 30 hours, resulting in 3-methoxy-5-aminomethyl-isoxazole (2) with a yield of 60%. 450px (2) was then refluxed in concentrated hydrochloric acid to hydrolyze the methoxy group, and the zwitterion crystallized from a solution of methanol and tetrahydrofuran after the addition of triethylamine, resulting in a 50% yield. 450px Chemists report having struggled to reproduce these results. More dependable and scalable procedures have been developed, two examples being the syntheses of McCarry and Varasi. McCarry’s synthesis is a three step synthesis involving a lithium acetylide produced from propargyl chloride. The acetylide (3), was dissolved in ether, cooled to -40 °C, and treated with excess ethyl chloroformate to afford ethyl 4-chlorotetrolate (4) in a 70% yield. (4) was then added to a solution of water, methanol and hydroxylamine at -35 °C . At a pH of between 8.5 and 9, the isoxazole (5) was recovered in a 41% yield.<unk>  was formed in a 65% yield when (5) was dissolved in a saturated solution of methanol and anhydrous ammonia and heated from 0 °C to 50 °C. The total yield was 18.7%. 750px Varasi’s synthesis is notable for its inexpensive starting materials and mild conditions. It begins with the combination of 2,3-Dichloro-1-propene (6), potassium bicarbonate, water, and dibromoformaldoxime (7), all dissolved in ethyl acetate. 5-Chloromethyl-3-bromoisoxazole (8) was extracted with an experimental yield of 81%. 5-Aminomethyl-3-bromoisoxazole (9) was formed in 90% yield by the combination of (8) and ammonium hydroxide in dioxane. 700px (9) was then refluxed with potassium hydroxide in methanol to generate 5-Aminomethyl-3-methoxyisoxazole (10) with a 66% yield. Subsequent reflux of (10) with hydrobromic acid and acetic acid generated<unk>  with a yield of 62%. The overall synthetic yield was 30%. 600px
Muscimol
Acetylcholine
Lysergic acid diethylamide
Anatoxin-a
Thiotepa
Opioid peptide
Neuropil
Procaine