| Identification | More | [Name]
5-Hydroxytryptophan | [CAS]
56-69-9 | [Synonyms]
2-AMINO-3-(5-HYDROXY-1H-INDOL-3-YL)PROPANOIC ACID
2-AMINO-3-(5-HYDROXY-1H-INDOL-3-YL)-PROPIONIC ACID
5-HYDROXY-DL-TRYPTOPHAN
5-HYDROXYTRYPTOPHAN
DL-2-AMINO-3-(5-HYDROXYINDOLYL)PROPIONIC ACID
DL-5-HTP
DL-5-HYDROXYTRYPTOPHAN
HYDROXYTRYPTOPHAN
TIMTEC-BB SBB003354
5-hydroxy-tryptopha
5-hydroxytryptophane
5-hydroxytrytophan
nci-c56644
5-HydroxyTryptophane (5-HTP)
5-Hydroxy-L-Tryptophan 5-Hydroxy-Tryptophan
DL-5-HYDROXYTRYPTOPHAN 99%
DL-5-HYDROXYTRYPTOPHAN, 99+% BY HPLC REFERENCE STANDARD
5-Hydroxytryptophan20%50%90%99%
5-Hydroxy-DL-tryptophane
5-Hydroxytryptophan(5-HTP) | [EINECS(EC#)]
200-284-8 | [Molecular Formula]
C11H12N2O3 | [MDL Number]
MFCD00005651 | [Molecular Weight]
220.22 | [MOL File]
56-69-9.mol |
| Chemical Properties | Back Directory | [Melting point ]
298-300°C | [Boiling point ]
361.16°C (rough estimate) | [density ]
1.484 | [refractive index ]
1.5200 (estimate) | [storage temp. ]
2-8°C | [solubility ]
DMSO (Slightly), Methanol (Slightly) | [form ]
solid | [pka]
2.22±0.10(Predicted) | [color ]
Off-White to Pale Beige | [Water Solubility ]
Soluble in water (4 mg/ml at 25°C), methanol. | [Merck ]
14,4847 | [BRN ]
88199 | [InChIKey]
LDCYZAJDBXYCGN-UHFFFAOYSA-N | [LogP]
-0.292 (est) | [CAS DataBase Reference]
56-69-9(CAS DataBase Reference) | [EPA Substance Registry System]
56-69-9(EPA Substance) |
| Hazard Information | Back Directory | [Description]
5-Hydroxytryptophan (5-HTP) is an aromatic amino acid naturally produced by the body from the essential amino acid L-tryptophan (LT). Produced commercially by extraction from the seeds of the African plant, Griffonia simplicifolia, 5-HTP has been used clinically for over 30 years. The clinical efficacy of 5-HTP is due to its ability to increase production of serotonin in the brain. | [Chemical Properties]
Off-White to Pale Beige Solid | [Originator]
Levotonine,Panmedica,France,1973 | [Uses]
A metabolite of Tryptophan | [Application]
5-hydroxytryptophan is a dietary supplement made from the seeds of the African plant Griffonia simplicifolia.
5-hydroxytryptophan has been used in alternative medicine as a possibly effective aid in treating depression or fibromyalgia.
Other uses not proven with research have included insomnia, alcohol withdrawal, headaches, premenstrual syndrome, binge-eating related to obesity, attention deficit disorder, and muscle spasms in the mouth.
5-hydroxytryptophan is often sold as an herbal supplement. There are no regulated manufacturing standards in place for many herbal compounds and some marketed supplements have been found to be contaminated with toxic metals or other drugs. Herbal/health supplements should be purchased from a reliable source to minimize the risk of contamination. | [Definition]
ChEBI: 5-hydroxytryptophan is a tryptophan derivative that is tryptophan substituted by a hydroxy group at position 5. It has a role as a human metabolite and a neurotransmitter. | [Preparation]
The synthesis of 5-hydroxytryptophan (5-HTP) by the condensation of 5-benzyloxygramine with diethyl formaminomalonate, followed by saponification, decarboxylation, and hydrogenolysis was described in 1951 and 1954 and was an application of gramine synthesis, developed by Snyder and Smith ten years before. A few years later, another application of gramine synthesis was reported. In the same year, Frangatos and Chubb reported an application of the convenient tryptophan synthesis developed ten years before by eliminating the difficult and tedious preparation of 5-benzyloxyindole. The p-benzyloxyphenylhydrazone of γ,γ-dicarbethoxy-γ-acetamido-butyraldehyde (I) was prepared and cyclized, without isolation, to form ethyl β-(5-benzyloxyindol-3-)-αcarbethoxy-α-acetamidopropioilate (II). Saponification and partial decarboxylation of II, followed by hydrolysis of the acetamido group, gave 5-benzyloxytryptophan (III). 5-HTP was obtained by hydrogenolysis of III (Figure 1). However, this synthetic method suffers from the difficulty involved in the regioselective hydroxylation of tryptophan.
synthesis of 5-hydroxytryptophan (5-HTP) | [Manufacturing Process]
Preparation of 4-benzyloxyphenylhydrazine: 200 grams 4-benzyloxyaniline
hydrochloride was suspended in a mixture of 264 ml concentrated
hydrochloric acid, 528 ml water and 732 grams crushed ice. A solution of 62.4
grams sodium nitrite in 136 ml water was added below the surface of the
stirred suspension at -10-(+/-)2°C during 10 minutes. After stirring for 1 hour
at 0°C, the suspension was treated with acid-washed charcoal and filtered.
The filtrate was cooled and maintained at -8°C while a solution of 500 grams
of stannous chloride in 760 ml concentrated hydrochloric acid was added with
stirring. The mixture was stirred for 2 hours at -8°C and the 4-
benzyloxyphenylhydrazine hydrochloride which separated was filtered off and
washed with water. The product was crystallized by adding 800 ml hot water
to a 3 liter solution in ethanol and had a MP of 185° to 189°C (yield 168.5
grams, 79%).
Preparation of Ethyl α-Acetylamino-α-Carbethoxy-β-(5-Benryloxy-Indolyl-3)-
Propionate: 4-benzyloxyphenylhydrazine hydrochloride was converted to the
corresponding base 2 to 3 hours before use: 28 grams of the hydrochloride
was suspended in 500 ml chloroform and shaken with 55 ml 2N sodium
hydroxide in 100 ml water. The chloroform was separated and the aqueous
phase reextracted with chloroform (2 x 100 ml). After washing with 100 ml
water, the chloroform solution was dried over sodium sulfate, filtered and
evaporated at 30° to 35°C, leaving 4-benzyloxyphenylhydrazine as a friable
buff-colored solid (23 grams, 97% from hydrochloride).
6.1 grams freshly distilled acrylic aldehyde (acrolein) in 9.7 ml chlorobenzene
was added at 30°C over 30 minutes to a stirred suspension of 24.2 grams
diethyl acetylaminomalonate in 37.5 ml chlorobenzene containing a catalytic
amount (0.25 ml) of 50% w/v aqueous sodium hydroxide. After a further 30
minutes the resultant solution was warmed and 23 grams 4-
benzyloxyphenylhydrazine was added at 45°C. The mixture was stirred and
heated at 65° to 70°C for 1 hour to complete condensation, when a red
solution was formed.
The resultant chlorobenzene solution was added to 440 ml N sulfuric acid and
the suspension was refluxed with stirring for 6 hours. The product was
extracted with chloroform (250 + 100 ml), and the chloroform solution
washed with water (3 x 100 ml), separated and dried over sodium sulfate.
After filtration and concentration at 40°C to 100 ml, 300 ml light petroleum
(BP 40° to 60°C) was added to the warm chloroform-chlorobenzene solution.
33.1 grams ethyl α-acetylamino-α-carbethoxy-β-(5-benzyloxyindolyl-3)-
propionate crystallized on cooling from the mixture. It was recrystallized by
dissolving in 200 ml benzene and adding 100 ml light petroleum (BP 60° to
80°C) at the boiling point. After cooling, the buff crystals were collected,
washed with cold benzene/light petroleum (1:1) mixture (50 ml), and dried at
55°C (yield 26.0 grams, 54%, MP 164° to 165°C).
Preparation of α-Acetylamino-α-Carboxy-β-(5-Benzyloxy-Indolyl-3)-Propionic
Acid: 18 grams ethyl α-acetylamino-α-carbethoxy-β-(5-benzyloxy-indolyl-3)-propionate was suspended in 85 ml water containing 8.5 grams sodium
charcoal. The suspension was refluxed for 4 hours, decolorizing charcoal
added, and the solution filtered hot through Hyflo Supercel.
After cooling in ice to 10°C, the solution was acidified with 24 ml concentrated
hydrochloric acid. The solid which separated was filtered off, washed with
water (3 x 30 ml) and dried in vacuo over silica gel, to give α-acetylamino-α-
carboxy-(5-benzyloxy-indolyl-3)-propionic acid, MP 144° to 146°C (15.0
grams, 95%) sufficiently pure for use in the next stage.
Preparation of α-Acetylamino-β-(5-Benzyloxy-Indolyl-3)-Propionic Acid: 15
grams α-acetylamino-α-carboxy-β-(5-benzyloxy-indolyl-3)-propionic acid was
suspended in 225 ml water and the suspension refluxed and stirred in a
stream of nitrogen until evolution of carbon dioxide ceased (about 2 hours).
After cooling somewhat, 120 ml ethyl alcohol was added and the suspension
refluxed until the product dissolved. Charcoal was added to the solutior the
mixture filtered hot, and the filter-cake washed with 50 ml hot 50% aqueous
ethanol. α-Acetylamino-β-(5-benzyloxy-indolyl-3)-propionic acid, MP 164° to
166°C, which crystallized from the filtrate on cooling, was collected, washed
with an ice-cold mixture of 15 ml ethanol and 45 ml water, and dried in vacuo
over silica gel (yield 11.1 grams, 83%).
Preparation of 5-Benzyloxytryptophan: 11 grams α-acetylamino-β-(5-
benzyloxy-indolyl-3)-propionic acid was suspended in a solution of 12 grams
sodium hydroxide in 90 ml water and refluxed for 24 hours. Charcoal was
added to the resultant solution and the mixture filtered hot. 150 ml 2N
hydrochloric acid was added to the filtrate at 70°C and 5-benzyloxytryptophan
crystallized on cooling. After washing with water and drying in vacuo over
silica gel, the amino acid (6.9 grams, 71%) had MP (sealed evacuated tube)
232°C, with softening, finally melting at 237° to 238°C (decomposition).
Charcoal was added to the filtrate, which was filtered hot and adjusted to pH
2. On cooling a second crop of 5-benzyloxytryptophan was obtained (2.2
grams, 23%), MP (sealed evacuated tube) 230°C, with softening, finally
melting at 233° to 237°C (decomposition). The overall yield of 5-
benzyloxytryptophan was 9.1 grams (94%).
Preparation of 5-Hydroxytryptophan: 0.4 gram palladium chloride and 1.7
grams acid-washed charcoal were suspended in 157 ml water and
hydrogenated at room temperature and atmospheric pressure until no further
hydrogen uptake occurred. A suspension of 14.2 grams 5-
benzyloxytryptophan in 175 ml ethyl alcohol was added and the mixture
hydrogenated under similar conditions. A hydrogen uptake slightly in excess of
theory was obtained. The suspension was warmed for a few minutes on the
steam bath and filtered hot. The filter-cake was washed with hot water (3 x
20 ml) and the filtrate evaporated to 20 ml under reduced pressure in a
nitrogen atmosphere.
The resultant mass of colorless crystals was triturated with 250 ml ice-cold
ethyl alcohol under hydrogen, filtered, and washed with cold ethyl alcohol (2 x
15 ml). The 5-hydroxytryptophan (6.9 grams, 69%) had MP (sealed
evacuated tube) 288°C, with softening, finally melting at 249° to 247°C
(decomposition). Concentration of the liquors under reduced pressure in a
nitrogen atmosphere, and trituration as before, gave a second crop (0.9 gram,
9%). The combined crops (7.8 grams) were dissolved in 120 ml hot water,
charcoal added, and the mixture filtered hot. The filtrate was concentrated in
a nitrogen atmosphere under reduced pressure and ethyl alcohol added. The
5-hydroxytryptophan then crystallized as colorless microneedles (6.5 grams,65%), had MP (sealed evacuated tube) 290°C, with slight softening, finally
melting at 295° to 297°C (decomposition). | [Therapeutic Function]
Antidepressant, Antiepileptic | [Biosynthesis]
5-Hydroxytryptophan, an intermediate molecule in the serotonin biosynthesis pathway, is formed by the addition of a hydroxyl (OH) group to the fifth carbon of the indole ring of tryptophan. It is used as an antiepileptic and antidepressant. | [Biochem/physiol Actions]
Immediate precursor of serotonin; L-aromatic amino acid decarboxylase substrate. | [Source]
5-HTP is derived from the Griffonia simplicifolia plant. Hypo-allergenic plant fiber is derived from pine cellulose. | [storage]
Store at -20°C | [Mode of action]
5-Hydroxytryptophan acts primarily by increasing levels of serotonin within the central nervous system. Other neurotransmitters and CNS chemicals, such as melatonin, dopamine, norepinephrine, and beta-endorphin have also been shown to increase following oral administration of 5-HTP. This ability to increase not only serotonin levels in the brain, but also dopamine and norepinephrine, allows 5-HTP to produce some significant and unique effects on brain chemistry and on serotonin-related conditions which other substances, including LT, cannot duplicate.? |
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