SYNTHESIS: A solution of 50 g myristicinaldehyde(3-methoxy-4,5-methylenedioxybenzaldehyde, see under MMDA for itspreparation) in 200 mL acetic acid was treated with 33 mL nitromethaneand 17.4 g anhydrous ammonium acetate and held on the steam bath for 5h. The reaction mixture was diluted with a little H2O and cooled inan external ice-acetone bath. A heavy crop of yellow crystals formed,which were removed by filtration, washed with cold acetic acid, anddried to constant weight. There was thus obtained 19.3 g3-methoxy-4,5-methylenedioxy-beta-nitrostyrene with a mp of 210-212 °C.The mother liquors were diluted with H2O, and extracted with 3x100 mLCH2Cl2. The pooled extracts were washed with 5% NaOH, and the solventremoved under vacuum yielding 34 g of a dark residue that was largelyunreacted aldehyde. This residue was reprocessed in acetic acid withnitromethane and ammonium acetate, as described above, and provided anadditional 8.1 g of the nitrostyrene with the same mp.
A suspension of 25 g LAH in 1.5 L anhydrous Et2O in an inertatmosphere was stirred magnetically, and brought up to a gentlereflux. Through a Soxhlet condenser modified to allow Et2O to returncontinuously to the reaction mixture, there was added 27.0 g of3-methoxy-4,5-methylenedioxy-beta-nitrostyrene. The addition requiremany h, and when it was completed, the reaction was held at reflux foran additional 9 days. After cooling the reaction mixture in anexternal ice bath, the excess hydride was destroyed by the cautiousaddition of dilute H2SO4. The final amount used was 1800 mL H2Ocontaining 133 g H2SO4. The phases were separated, and the aqueousphase was washed with 2x100 mL Et2O. To it was then added 625 gpotassium sodium tartrate, and sufficient base to bring the pH to >9.This was extracted with 3x250 mL CH2Cl2, and the pooled extractsstripped of solvent under vacuum. The residue was dissolved inanhydrous Et2O and saturated with anhydrous HCl gas, giving a heavycrystallization of salts. These were removed by filtration, Et2Owashed, and air dried, to give 17.7 g3-methoxy-4,5-methylenedioxyphenethylamine (LOPHOPHINE) as anoff-white solid with a mp of 160-161 °C. This was dissolved in CH3CNcontaining 5% EtOH, decolorized with activated charcoal, filtered, andthe removed charcoal washed with boiling CH3CN. Slow cooling of thesolution provided 11.7 g of a white product which melted at 164-164.5°C.
DOSAGE: greater than 200 mg.
DURATION: unknown.
QUALITATIVE COMMENTS: (with 150 mg) Between two and five hours, verypeaceful and euphoric mood elevation, similar to mescaline, butwithout any visual distortion. Mild enhancement of color perception,possibly a function of mood elevation. There was no nausea, noeyes-closed vision. Slept easily that evening.
(with 250 mg) Possibly something of a threshold effect from 2:30 to4:30 of the experiment. Intangible, and certainly there is nothing anhour later.
EXTENSIONS AND COMMENTARY: It looks as if this compound is not active.There is an excellent argument as to why it really should be, and thefact that it is not active is completely unexpected. Let me try toexplain.
Quite simply, mescaline is a major component and a centrally activealkaloid of the Peyote plant. It is a phenethylamine, which canundergo a cyclization within the plant to produce a pile ofderivatives (tetrahydroisoquinolines) such as anhalonine andO-methylanhalonidine that are marvelously complex alkaloids, allnatural components of this magical cactus. But there is another pileof derivatives (tetrahydroisoquinolines) such as anhalonine, andlophophorine, and peyophorine which are the logical cyclizationproducts of another phenethylamine which does not exist in the cactus.It should be there, but it is not. If it were there it would be thenatural precursor to a host of bicyclic alkaloids, but it is absent.This is 3-methoxy-4,5-methylenedioxyphenethylamine. I feel that someday it will be discovered as a plant component, and when it is it canbe given a name that reflects the generic binomial of the plant. Andsince the plant has been known as Lophophora williamsii, why not givea name to this compound (which should be in the plant), one derivedfrom the Latin name, but one that has never before been used? Whatabout LOPHOPHINE? And so, I have named it, but I have not found it,nor has anyone else. Yet.
It is inevitable that this simple and most appealing precursor will befound to be present in the cactus, at some future time when we willhave tools of sufficient sensitivity to detect it. And certainly, itwould be reasonable to expect it to be an active psychedelic, and tobe as interesting in man as its close cousin, mescaline. But, at thepresent time, LOPHOPHINE is not known to be present in the plant, andit is not known to be active in man. I am confident that bothstatuses will change in the future.
Back]
]