5-Hydroxytryptamine acetylation

The values of the 1-hydroxy moiety of (5)-(- -)-iVb-acetyl- 1-hydroxytrypto-phan methyl ester (32), methyl l-hydroxyindole-3-butylate (33), iVb-methoxy-carbonyl-l-hydroxytryptamine (34), 1-hydroxymelatonm (19), l-hydroxy-6-nitroindole (35), and l-hydroxy-5-nitroindole (36) are determined to be 9.8, 8.4, 8.2, 8.1, 6.9, and 6.8, respectively (Fig. 2) (2000H1881). Thus, 1-hydroxyindoles are weak acids, stronger than phenol and weaker than succinimide. Therefore,... 

Michael addition reaction of 1-hydroxytryptamines to Q ,/3-unsaturated carbonyl compounds is worthy of note (99H2815). Addition of Ab-acetyl- 1-hydroxy-tryptamine (39) to methyl acrylate and methyl crotonate in the presence of... 

The reaction of Ab-acetyl-1 -hydroxytryptamine (39) with mesyl chloride (MsCl) in THF in the presence of EtsN provides 1-acetyl-1,2,3,8-tetrahydropyrrolo[2,3-(j] indole (49a, 35%) (70JA343), Ab-acetyl-6-mesyloxytryptamine (50a, 4%), Ab-acetyl-2,3-dihydro-2-oxotryptamine (51a, 5%), l-acetyl-3a-(4-chlorobutoxy)-l,2,3,3a,8,8a-hexahydropyrrolo[2,3-(j]indole (52a, 7%), and Ab-acetyltryptamine (53a, 2%) as shown in Scheme 6 (2000H483). In the same reaction with MsCl, l-hydroxy-Ab-methoxycarbonyltryptamine (34) produces 50b (7%), 51b (34%), and 52b (9%), while the formation of 49b is not observed at all. In the case of Ab-trifluoroacetyl-l-hydroxytryptamine (48), 49c (45%), 50c (8%), 51c (4%), and 52c (6%) are produced. These data suggest that the yield of 49 increases, whereas the yield of 51 decreases in the order of electron-withdrawing ability of Ab substituents (COOMe < COMe < COCF3). Stability of 49 seems to govern the quantity of 51, which is probably formed by hydrolysis of 49. 

Klemm, P., Hecker, M., Stockhausen, H., Wu, C. C., Thiemermann, C., Inhibition by N-acetyl-5-hydroxytryptamine of nitric oxide synthase expression in cultured cells and in the anaesthetized rat, Br. 

Serotonin is an indolamine neurotransmitter, derived from the amino acid L-tryptophan. Tryptophan is converted to 5-hydroxytryptophan (5-HTP) by tryptophan hydroxylase. 5-HTP is converted to 5-hydroxytryptamine (serotonin, 5-HT) by aromatic amino acid decarboxylase. In the pineal gland, 5-HT may be further converted to /V-acetyl serotonin by 5-HT /V-acetyltransferase and then to melatonin by 5-hyroxyindole-O-methyltransferase. 5-HT is catabolized by monoamine oxidase, and the primary end metabolite is 5-hydroxyindoleacetic acid (5-HIAA). 

The known pentacyclic lactam (219), prepared from 2-hydroxytryptamine and dimethyl 4-ethyl-4-formylpimelate, has been used in an improved synthesis of ( )-quebrachamine.106a Conversion of (219) into the thiolactam, acetylation to (220), desulphurization, and hydrolysis yielded 1,2-dehydroaspidospermidine (221), which on reduction gave ( )-quebrachamine (222) (Scheme 31). A new synthesis of the tetracyclic amino-alcohols (223) constitutes another formal synthesis of quebrachamine.1066... 

N-Acetyltransferase uses acetyl-CoA to acetylate the amino moiety of arylal-kylamines. In mammalian pineal gland, this enzyme catalyzes the production of N-acetyl-5-hydroxytryptamine, which is the precursor of melatonin. It is also involved in the inactivation of monoaminergic neurotransmitters in insects. 

Substrates (p-octopamine, dopamine, or 5-hydroxytryptamine) were separated from their N-acetylated products on an Ultrasphere I.P. C18 column (4.6 mm x 250 mm, 5 pm). The mobile phase was comprised of 75 mAf monobasic sodium phosphate, 1 pAf EDTA, 0.35 mAf 1-octanesulfonate (sodium salt), 11% methanol, and 4% acetonitrile. Coulometric detection was used. Detection of p-octopamine and its N-acetylated product was achieved at a potential of +0.75 V, while dopamine, 5-hydroxytryptamine and their products were detected at +0.50 V. 

Apart from the relatively small amounts that are required for synthesis of the neurotransmitter serotonin (5-hydroxytryptamine), and for net new protein synthesis, essentially the whole of the dietary intake of tryptophan is metabolized by way of the oxidative pathway shown in Figures 8.4 and 9.4, which provides both a mechanism for total catabolism by way of acetyl coenzyme A and a pathway for synthesis of the nicotinamide nucleotide coenzymes (Section 8.3). 

C12H14N202 N-acetyl-5-hydroxytryptamine 17994-17-1 25.00 1.1608 2 24097 C12H15N08 4-mtrophenyl-a-D-glucopyranoside 3767-28-0 25.00 1.3572 2... 

The basal ganglia also contain relatively large amounts of 5-hydroxytryptamine, substance P and acetylcholine. The caudate nucleus has a higher acetylcholine and choline acetyl transferase activity than has any... 

The first compound having an ethyl side chain to be synthesized by this method was a compound in the pseudo -Aspidosperma series (204). The key compound in this sequence is the vinylogous amide 414, which was prepared from 2-hydroxytryptamine hydrochloride (406) and 3-oxobutanal ethylene ketal (407), followed by hydrolysis, cyclization with the Meerwein reagent, and acetylation (205). 

Leptodactylus pentadactylus and L. ocellatus native to South and Central America, contain considerable amounts of 5-hydroxytryptamine derivatives, like N-methylserotonine, bufotenin and bufotenidin as well as leptodactylin and candicin (ref. 4). Of a new type are substances like histamin, methyl-, and acetyl-histamins, and spinaceamin. Spinaceamin can be synthesized in vitro by a biomimetic reaction of histamin and formaldehyde in aqueous solution at pH 6.8, and room temperature (ref. 5). 

Fic. 1. Metabolism of tryptophan to serotonin (5-hydroxytryptamine) and niacin. Fyiidoxal phosphate (PLP) dependent reactions are indicated. Reactions not shown which may result in formation of products excreted in urine include the acetylation of liymuenine and 3-hydroxykynurenine, conjugation of anthranilic acid with glycine (to form o-aminohippuric acid) and with glucuronic acid, and the dehydroxylation of kynurenic acid and xanthurenic add to quinaldic add and 8-hydroxyquinaldic add, respectively. 

Acetylcholine is formed from choline (which is also an important constituent of phospholipids) and acetyl CoA under the catalytic influence of choline acetyl-ase. It is hydrolised by acetylcholinesterase or choline esterase. Two important steps in the formation of noradrenaline from tyr dopa decarboxylase and dopamine hydroxylase. Adrenaline is formed from noradrenaline by phenyl ethanolamine A -methyltransferase. Both noradrenaline and adrenaline are metabolised by catechol 0-methyl transferase or monoamine oxidase. Some later steps in their metabolism involve aldehyde dehydrogenase and alcohol dehydrogenase (aldehyde reductase), After hydroxylation to its 5-hydroxy derivative, tryptophan is converted by 5-hydroxytryptophan decarboxylase to 5-hydroxytryptamine (serotonin). The major routes of serotonin metabolism involve either monoamine oxidase or hydroxyindole 0-methyltransferase. Histamine is synthesised from histidine by histidine decarboxylase, and is metabolised by either diamine oxidase or histamine Af-methyltransferase. Gamma aminobutyric acid is formed by glutamate decarboxylase and metabolised by... 

M is synthesized from serotonin by acetylation to A-acetyl rotonin, followed by methylation (catalysed by acetylserotonin methyltransferase, EC 2.1.1.4) to M.In the pineal gland M. biosynthesisis is controlled by epinephrine, which stimulates adenylate t clase (EC 4.6.1.1), which in turn stimulates protein kinase. The first three steps of M. synthesis (L-tryptophan S-hydroxytryptophan -> serotonin - A-acetyl-5-hydroxytryptamine) are promoted in this way, but the methyltransferase is not affected. However, the rate-limiting step is catalysed by serotonin A-acetyltransferase. M. is inactivated and excreted as 6-hydroxymelatonin, or as 5-methoxyindole-acetic acid. 

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