Benzyl isoquinoline alkaloids are made from tyrosine
المؤلف:
Jonathan Clayden , Nick Greeves , Stuart Warren
المصدر:
ORGANIC CHEMISTRY
الجزء والصفحة:
ص1159-1160
2025-08-15
409
Benzyl isoquinoline alkaloids are made from tyrosine
The benzyl isoquinolines are another family of alkaloids of rather different structure. They all have a benzyl group attached to position 2 of an isoquinoline ring. Usually the alkaloids are oxygenated on the benzene ring and many are found in opium poppies (Papaver somniferum). For all these reasons papaverine is an ideal example.
Labelling shows that these alkaloids come from two molecules of tyrosine. One must lose CO2 and the other NH3. We can easily see how to divide the molecule in half, but the details will have to wait a moment.
The question of when the extra OH groups are added was also solved by labelling and it was found that dihydroxyphenyl pyruvate (DHPP) was incorporated into both halves but the dihydroxyphenylalanine (an important metabolite, and also a useful medicine, usually called dopa) was incorporated only into the isoquinoline half.
The amino acid and the keto-acid are related by a pyridoxal-mediated transaminase and the hydroxylation must occur right at the start.
Pyridoxal-mediated decarboxylation of dopa gives dopamine and this reacts with the keto acid to form an iminium ion perfectly placed for an intramolecular electrophilic aromatic substitution by the electron-rich dihydroxyphenyl ring.
This closes the isoquinoline ring in a Mannich-like process with the phenol replacing the enol in the pyrrolidine alkaloid biosynthesis.
The cyclization product is still an amino acid and it can be decarboxylated by pyridoxal. Now we have something quite like papaverine but it lacks the methyl groups and the aromatic heterocyclic ring, which are introduced by methylation with SAM and oxidation.
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