3-Methoxy-4,5-dihydroxyphenethylamine (3-MeO-4,5-diOH-PEA), also known as 4-O-,5-O-didesmethylmescaline, is a phenylethylamine alkaloid and an important intermediate metabolite in the final biosynthesis of mescaline in the peyote cactus (Lophophora williamsii), as well as in other cacti such as Echinopsis pachanoi, Echinopsis lageniformis, and Echinopsis peruvianus. It was found in Beta vulgaris as a metabolite.
Mescaline biosynthesis in Lophophora williamsii begins with the conversion of <small>L</small>-tyrosine to L-DOPA by LwCYP76AD94, which is decarboxylated to dopamine (LwTYDC), which is then 3-O-methylated to 3-methoxytyramine by one of two O-methyltransferases (LwOMT2 or LwOMT6), 5-hydroxylated by cytochrome CYP76AD131 to 3-methoxy-4,5-dihydroxyphenylethylamine, then methylated by LwOMT2 at position 5 to form 3,5-dimethoxy-4-hydroxyphenylethylamine and finally by LwOMT10 at position 4 to form mescaline.
3-Methoxy-4,5-dihydroxyphenethylamine is the primary intermediate in the synthesis of Lophophora williamsii tetrahydroisoquinoline alkaloids. This process likely involves the enzyme LwOMT10, which catalyzes methylation at position 4 or 5 to yield 3,4-dimethoxy-5-hydroxyphenethylamine. The latter is subsequently N-methylated by LwNMT to form N-methyl-3,4-dimethoxy-5-hydroxyphenethylamine, which is eventually converted into lophophorine.
3-Methoxy-4,5-dihydroxyphenethylamine has been found in Senegalia berlandieri, Echinopsis spachiana, Austrocylindropuntia cylindrica,Beta vulgaris, and Vachellia rigidula and was identified as an important intermediate metabolite in Lophophora williamsii.