                              MUSCIMOLE
    
    Muscimole can be found in the mushroom species Amanita muscaria (fly
agaric). It is a powerful drug (e.g., 10 mg for oral dose) but its
synthesis is rather difficult. I feel that there are better drugs that can
be made much more easily and cheaply, so I have only included two formulas
for the drug. The first formula uses ibotenic acid for a starting material.
To make ibotenic acid requires more work than to make muscimole, but
ibotenic acid can be purchased from many suppliers at a lower cost than to
synthesize muscimole. Ibotenic acid is stocked by Aldrich, Sigma, Chemical
Dynamics, Regis Chemical Reagents, etc. Look in Chemical Sources for more
suppliers and then call for the best price, as sometimes there is a large
price difference. Ibotenic is not a psychedelic (not a useful one anyway),
so you could purchase it without alerting the DEA. The last I heard,
muscimole is not illegal either, so you may be able to order that through
the mail also.
    
    Muscimole from Ibotenic Acid. Reflux ibotenic acid in 10 times its
weight of water.
    
    Muscimole. CA, 65, 2266 (1966). Dissolve 626 g of 2-(2-nitrovinyl)
furan in 3.1 liters of 48% HBr and 6.25 liters glacial acetic acid, then
heat on steam bath for 9 hours. Concentrate by evaporating in vacuo to 3
liters. Add 3 liters of water, boil and add decolorizing carbon, filter
hot, cool, and filter again. Extract the filtrate with 2 liters of
chloroform using small portions.

    Add residue to the precipitate and recrystallize with benzene-cyclo-
hexane to get intermediate. 44 g of the above intermediate is added to 440
ml coned sulfuric acid and add 80 g of CrO3 (that has been added to 80 ml
of water) dropwise over three hours while maintaining a temp of 15- 20ø.
Pour onto 800 g of ice and extract the aqueous solution with three 500 ml
portions of ether. Evaporate the ether in a vacuum to get 3-Br-isoxazole-
5-COOH and recrystallize from benzene-toluene to purify. Dissolve 30 g of
this above product in 500 ml methanol along with 27 g of KOH and stir for 2
hours at 140ø. Cool and add l~h liters of water and extract with three l'h
liter portions of ether. If you encounter much color, you should boil for a
short time with a small amount of decolorizing carbon, then filter hot and
acidify with small portions of concentrated HC1 acid. Filter cool and
recrystallize with benzene to get 3-methoxy-isoxazole-5-COOH. Dissolve 5.2
g of this last compound with 100 ml of 3% HCl acid in methanol and reflux
for 3 hours. Evaporate in vacuo and recrystallize the residue with
petroleum ether. Add 0.8 g of the recrystallized product with stirring to
40 ml of aqueous ammonia (have a density of .90) and stir for 30 min at
room temp. Filter and wash with cold water, then dry, to get 500 mg of
product, which is a carboxamide. Dissolve 37.8 g of NaBH4 in 100 ml of
diglyme and 32 ml BF3 etherate in diglyme, then add to 4.6 g of the
carboxamide above in 100 ml of tetrahydrofuran and reflux for 48 hours. Add
hydrogen chloride (HCl acid), evaporate in vacuo and dissolve the residue
in water. Basify with 50% KOH and extract with ether, dry, filter,
evaporate in vacuo to get intermediate. One g of this intermediate is added
to 10 ml of glacial acetic acid and 4.5 g of HBr and reflux for 1 hour.
Evaporate to get muscimole. As you can see, this is a long, drawn out
process that is not worthwhile in cost or yield. I figured that, for the
price of the chemicals, you could buy 4 or 5 times as much ibotenic acid
and save your self days of hard work, plus gain much more product than the
formula could ever give. There are lots of different formulas, but the
result is the same.
