Methyl l-hydroxyindole-3-acetate

Reduction of 46b with EtsSiH/TFA produces similarly N-methyl-bis-2,3-dihydroindole (47b, 85%). Employing the tungstate method, 47a,b and 48 are converted to N-[2-(l-hydroxyindol-3-yl)ethyl]-l-hydroxyindole-3-acet-amides (49a, 51% 49b, 39%) and N-[2-(l-hydroxyindol-3-yl)ethyl]indole-3-acetamide (50, 55%), respectively. Subsequent methylation of 49a,b and 50 affords 43a (91%), 43b (72%), and 51 (100%). 

Serotonin, or 5-HT, is biosynthesized (3) from its dietary precursor L-tryptophan (Fig. 14.1). Serotonergic neurons contain tryptophan hydroxylase (L-tryptophan-5-monooxygenase) that converts tryptophan to 5-hydroxytryptophan (5-HTP) in what is the rate-limiting step in 5-HT biosynthesis and aromatic L-amino acid decarboxylase (previously called 5-HTP decarboxylase) that decarboxylates 5-HTP to 5-HT. This latter enzyme also is responsible for the conversion of L-DOPA to dopamine (see Chapter 12). The major route of metabolism for 5-HT is oxidative deamination by monoamine oxidase (MAO-A) to the unstable 5-hydroxyindole-3-acetaldehyde, which is either reduced to 5-hydroxytryptophol ( 15%) or oxidized to 5-hydroxyindole-3-acetic acid ( -85%). In the pineal gland, 5-HT is acetylated by 5-HT N-acetyltransferase to N-acetylserotonin, which undergoes O-methylation by 5-hydroxyindole-O-methyltransferase to melatonin. 

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