Pyridoxine

Structural formula
General
Common name	Pyridoxine
other names	4,5-bis (hydroxymethyl) -2-methyl-3-pyridinol ( IUPAC ); Adermin; Pyridoxole;
Molecular formula	C 8 H 11 NO 3
CAS number	65-23-6; 58-56-0 ( hydrochloride );
ATC code	A11 HA02
Brief description	colorless solid
Occurrence	Wheat germ , salmon , walnut
physiology
function	Coenzyme in various enzymatic reactions, especially in amino acid metabolism
Daily need	1.6-1.8 mg
Consequences in case of deficiency	Diarrhea and vomiting, dermatitis, convulsive states, neurological disorders
Overdose	> 500 mg d −1
properties
Molar mass	169.18 g mol −1
Physical state	firmly
Melting point	159-162 ° C
solubility	soluble in water (120 g l −1 at 20 ° C)
safety instructions
	Please note the restricted labeling requirements for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances	no GHS pictograms
	no GHS pictograms
H and P phrases	H: no H-phrases
	P: no P-phrases
Toxicological data	4000 mg kg −1 (rat perorally ); 657 mg kg −1 (rat intravenous ); 645 mg kg −1 (mouse intravenous ); 4000 mg kg −1 (rat perorally , hydrochloride ); 530 mg kg −1 (rat intravenous , hydrochloride ); 5500 mg kg −1 (mouse perorally , hydrochloride ); 660 mg kg −1 (mouse intravenous , hydrochloride );
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Pyridoxine (outdated also Adermin ) is a solid, water-soluble chemical compound that is a vital compound among the vitamins .

Along with their derivatives pyridoxal (with aldehyde function) and pyridoxamine (with amino group ) which in vivo are easily transformed into each other, they form the group of vitamin B ₆ . The active form of the vitamin B ₆ group is called pyridoxal phosphate . Its heterocyclic ring is that of pyridine .

history

The physiological importance of pyridoxine was discovered by Paul György in dietary feeding experiments on rats in 1934 and the compound was first presented in crystalline form in 1938. His constitution was fully clarified just a year later. The mechanism of the effect was clarified in particular by Alexander E. Braunstein in the 1950s. Today pyridoxine is counted as vitamin B ₆ in the group of B vitamins and, like its hydrochloride, is used as a medicinal substance.

synthesis

Synthesis according to Roche / DSM

The starting point here is ethyl 2-chloroacetoacetate , which is condensed with formamide to give the 4-methyloxazole-5-carboxylic acid ester. In the next step, the amide is formed from this with ammonia and then converted into nitrile with phosphorus pentoxide . The 4-methyloxazole-5-carbonitrile thus formed reacts in a Diels-Alder reaction with the cyclic ketal of 2-butene-1,4-diol at 180 ° C. to form the primary adduct, which, with elimination of hydrogen cyanide, gives the cyclic ketal of pyridoxine with acetone . Finally, acidic cleavage yields pyridoxine.

Synthesis according to MSD

The company MSD starts with racemic DL - alanine , which is esterified with ethanol and HCl to form the ethyl ester hydrochloride. The next step with formamide is the N -formyl- DL -alanine ethyl ester, which reacts with phosphorus pentoxide to form 5-ethoxy-4-methyloxazole. This is reacted with 2-isopropyl-4,7-dihydro-1,3-dioxepine, the acetal of 2-butene-1,4-diol and isobutyraldehyde , at 180 ° C. and subsequent acidic cleavage to form pyridoxine.

Synthesis according to BASF

In the BASF method , the methyloxazole-5-carboxylic acid ester is first hydrolyzed under alkaline conditions and then decarboxylated with the addition of heat . The 4-methyloxazole formed is reacted with 3-methylsulfonyl-2,5-dihydrofuran to give 6-methyl-1,3-dihydrofuro [3,4- c ] pyridin-7-ol. This is split with hydrochloric acid to form the end product.

Pyridoxine and dream experience

A 2002 study with 12 volunteers reported that taking 250 mg of pyridoxine daily at bedtime resulted in a stronger dream experience after three days . These results were validated by a randomized , double-blind , placebo- controlled follow-up study (2018) with 100 test subjects.

literature

Kleemann, Engel: Pharmaceutical Substances , 3rd Edition; Thieme Verlag 1999
Auterhoff , Knabe, Höltje: Textbook of Pharmaceutical Chemistry , 14th edition; Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart 1999
Eger, Troschütz, Roth: drug analysis , 4th edition; Deutscher Apotheker Verlag, Stuttgart 1999
Kleemann, Roth: Drug Production ; Thieme Verlag 1983

Web links

Wikibooks: Biochemistry and Pathobiochemistry: Pyridoxal Phosphate Metabolism - Learning and Teaching Materials

Individual evidence

↑ ^a ^b ^c ^d ^e data sheet Pyridoxine, ≥98% from Sigma-Aldrich , accessed on June 25, 2017 ( PDF ).
↑ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j A. Kleemann , J. Engel, B. Kutscher, D. Reichert: Pharmaceutical Substances - Synthesis, Patents, Applications. 4th edition. Thieme 2001, ISBN 3-13-115134-X .
↑ M. Ebben, A. Lequerica, A. Spielman: Effects of pyridoxine on dreaming: a preliminary study. In: Perceptual and motor skills. Volume 94, Number 1, February 2002, pp. 135-140, PMID 11883552 .
↑ Denholm J. Aspy, Natasha A. Madden, Paul Delfabbro: Effects of Vitamin B6 (Pyridoxine) and a B Complex Preparation on Dreaming and Sleep. In: Perceptual and Motor Skills. 2018, p. 003151251877032, doi : 10.1177 / 0031512518770326 .

[Sigma-1] ↑ ^a ^b ^c ^d ^e data sheet Pyridoxine, ≥98% from Sigma-Aldrich , accessed on June 25, 2017 ( PDF ).

[Kleemann-2] ↑ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j A. Kleemann , J. Engel, B. Kutscher, D. Reichert: Pharmaceutical Substances - Synthesis, Patents, Applications. 4th edition. Thieme 2001, ISBN 3-13-115134-X .

[PMID11883552-3] M. Ebben, A. Lequerica, A. Spielman: Effects of pyridoxine on dreaming: a preliminary study. In: Perceptual and motor skills. Volume 94, Number 1, February 2002, pp. 135-140, PMID 11883552 .

[DOI10.1177/0031512518770326-4] Denholm J. Aspy, Natasha A. Madden, Paul Delfabbro: Effects of Vitamin B6 (Pyridoxine) and a B Complex Preparation on Dreaming and Sleep. In: Perceptual and Motor Skills. 2018, p. 003151251877032, doi : 10.1177 / 0031512518770326 .