2-amino-1,3-propanediol

Structural formula
General
Surname	2-amino-1,3-propanediol
other names	2-aminopropane-1,3-diol Serinol 1,3-dihydroxyisopropylamine 2-aminoglycerin
Molecular formula	C 3 H 9 NO 2
Brief description	White dust
External identifiers / databases
CAS number 534-03-2 EC number 208-584-0 ECHA InfoCard 100.007.805 PubChem 68294 ChemSpider 61591 Wikidata Q16068659
properties
Molar mass	91.11 g mol −1
Physical state	firmly
density	1.1278 g cm −3 at 25 ° C
Melting point	52.25 ° C
boiling point	116 ° C at 0.1 kPa 274 ° C with decomposition
solubility	very soluble in water (364 g · l-1 at 20 ° C), soluble in methanol
Refractive index	1.4698 (25 ° C, 589 nm)
safety instructions
GHS labeling of hazardous substances danger H and P phrases H: 318 P: 280-305 + 351 + 338
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . Refractive index: Na-D line , 20 ° C

2-Amino-1,3-propanediol ( Serinol ) is an amino alcohol with one secondary amino group and two primary hydroxyl groups . Serinol is derived from the α - amino acid serine or from glycerine , the secondary hydroxyl group of which has been replaced by an amino group. 2-Amino-1,3-propanediol has gained some importance as a synthetic building block, especially for drugs .

Occurrence and representation

2-Amino-1,3-propanediol occurs naturally in sugar cane (Saccharum officinarum) and is an intermediate stage in the biosynthesis of the so-called rhizobitoxins, which are formed by some phytopathogenic fungi and which inhibit the synthesis of ethylene in the plant host organism.

Sphingolipids , such as sphingosine and especially N -acylated derivatives, such as. As ceramides , sphingomyelins , cerebrosides and gangliosides contain all the structural element 2-amino-1,3-diol and play in the lipid signaling (Engl. Lipid signaling ) as a second messenger in eukaryotes an important role.

The multiple sclerosis drug fingolimod and the antibiotic chloramphenicol also contain serinol as a structural element, without 3-amino-1,3-propanediol itself appearing as a molecular component in the biosynthesis of chloramphenicol and the various chemical routes.

The first chemical synthesis of 2-amino-1,3-propanediol was described in 1897 by Oskar Piloty and Otto Ruff .

On a laboratory scale, the oxime of dihydroxyacetone was reduced to the amine with sodium amalgam in the presence of aluminum sulfate . A modern variant uses the heterogeneous catalytic hydrogenation of the oxime on a rhodium catalyst on aluminum oxide (90% crude yield) and should also be suitable for the industrial scale.

The precursor dihydroxyacetone can also be hydrogenated directly with liquid ammonia in methanol with Raney nickel as a catalyst via the intermediate stage of the imine to form serinol.

The crude product obtained in 99% yield is converted into the oxalate for purification with oxalic acid dihydrate.

The 2-nitro-1,3-propanediol, accessible from nitromethane by reaction with twice the molar mass of paraformaldehyde , can be used as a sodium salt (explosive in the dry state) on an industrial scale in a loop reactor with exact dosage and temperature control on a palladium contact practically quantitatively and can be hydrogenated to serinol in high purity.

Also from nitromethane by complete replacement of the hydrogen atoms of the activated methyl group by hydroxymethyl groups obtained tris (hydroxymethyl) -nitromethan can after blocking of two hydroxymethyl groups by ketal formation with acetone , removal of the third hydroxymethyl group in the alkaline range, hydrogenation of the nitro to the amino group and removal of the protecting group in Acids in a total yield over four stages of approx. 66% and rather less suitable for an industrial process.

The dihydroxyacetone, which is derived from the natural and cheap raw material glycerine and produced using efficient processes, appears to be the most suitable starting material for the production of serinol because of its short synthesis routes with unproblematic reactants and reaction conditions.

properties

2-Amino-1,3-propanediol is a white, odorless crystal powder that dissolves very well in water, as well as in methanol and DMSO . The substance is hygroscopic and is particularly corrosive to the eye.

Applications

The amide of arachidonic acid with 2-amino-1,3-propanediol, known as arachidonoylserinol, is the N- analogue of 2-arachidonylglycerol (2-AG), the natural endocannabinoid ligand for the cannabinoid receptor 1 CB1 .

Arachidonoylserinol is much more stable than the glycerin derivative, but less active than 2-AG by at least a power of ten.

The nucleoside uridine is said to reduce the in vivo toxicity of the cytostatic 5-fluorouracil without reducing its cytotoxicity . Since high doses of uridine are poorly tolerated, the targeted inhibition of the inactivating enzyme uridine phosphorylase ( human uridine phosphorylase hUP) should increase the uridine level in the organism. Uracil derivatives with a 2-amino-1,3-propanediol function were particularly effective as hUP inhibitors .

Recently, surfactant-like antimicrobial substances were described in which two head groups, each triple positively charged , are linked to a long (C ₁₆ or C ₁₈ ) carboxylic acid via 2-amino-1,3-propanediol . The quaternary ammonium compounds obtained are effective in vitro against gram-positive bacteria , including multi-resistant problem strains .

The water-insoluble isophthalic acid precursor of the iodine - containing X - ray contrast agent iopamidol becomes readily water-soluble by amidation with 2-amino-1,3-propanediol.

A multi-step synthesis of the iminosugar 1-deoxygalactonojirimycin , a competitive inhibitor of the enzyme α-galactosidase A , starts from N - benzoyl -protected and O - TBS-protected serinol.

The cyclohexane derivative voglibose is an antidiabetic of the α-glucosidase inhibitor type, such as. B. acarbose and miglitol . The synthesis starts from valiolamine, a so-called aminocyclitol, which, like the immunosuppressant sirolimus , can be isolated from Streptomyces hygroscopicus .

The amino group of Valiolamins is reacted with 3,5-di- tert .-Butyl-1,2-benzoquinone DBQ for imine oxidized hydrolyzes the imine to the corresponding ketone (Valiolone) and then with serinol in the presence of sodium cyanoborohydride reducing under acidic aminated .

Individual evidence

1. ↑ ^{a b c d e f} Entry on 2-aminopropane-1,3-diol in the GESTIS substance database of the IFA , accessed on April 10, 2020 (JavaScript required)
2. ^ ^{A b} Carl L. Yaws: Thermophysical Properties Ob Chemicals and Hydrocarbons, 2nd Edition . Elsevier Inc., Amsterdam, NL 2015, ISBN 978-0-12-800834-8 , pp. 36 .
3. ↑ ^{a b} Entry on 2-Amino-1,3-propanediol at TCI Europe, accessed on April 9, 2020.
4. ↑ ^{a b} B. Andreeßen, A. Steinbüchel: Serinol: small molecule - big impact . In: AMB Express . tape 1 , 2011, p. 12 , doi : 10.1186 / 2191-0855-1-12 .
5. ↑ O. Piloty, O. Ruff: About some aminol alcohols of the fatty series . In: Ber. German Chem. Ges. Volume 30 , no. 2 , 1897, p. 2057-2068 , doi : 10.1002 / cber.189703002181 .
6. ↑ Patent US5922917A : Process for the preparation of 2-amino-1,3-propanediol. Applied on April 5, 1995 , published on July 13, 1999 , applicant: Bracco International BV, inventor: A. Nardi, M. Villa. ‌
7. ↑ Patent EP0238961A2 : Process for the production of hydroxyamines. Registered on March 14, 1987 , published on September 30, 1987 , applicant: Merck Patent Gesellschaft mbH, inventors: E. Felder, M. Römer, H. Bardonner, H. Härtner, W. Fruhstorfer. ‌
8. ↑ Patent US4448999 : Process for the preparation of 2-aminopropanediol-1,2 (serinol). Applied on July 30, 1982 , published on May 15, 1984 , Applicant: Dynamit Nobel AG, Inventor: K. Thewalt, G. Bison, H. Egger. ‌
9. ↑ Patent EP0348223A2 : Novel process for the preparation of serinol. Filed June 23, 1989 , published December 27, 1989 , Applicant: WR Grace & Co.-Conn., Inventor: JM Quirk, SG Harsy, CL Hakansson. ‌
10. ↑ M. Pagliaro, R. Ciriminna, H. Kimura, M. Rossi: From glycerin to higher quality products . In: Angew. Chem. Band 119 , no. 24 , 2007, pp. 4516–4522 , doi : 10.1002 / anie.200604694 .
11. ↑ F. Ulgheri, P. Spanu: An efficient chemical conversion of glycerol to dihydroxyacetone . In: ChemistrySelect . tape 3 , no. 41 , 2018, p. 11569–11572 , doi : 10.1002 / slect.201802841 .
12. ↑ Entry on 2-aminopropane-1,3-diol at Toronto Research Chemicals , accessed April 10, 2020 ( PDF ).
13. ↑ AD Khanolkar, V. Abadji, S. Lin et al .: Head group analogs of arachidonylethanolamide, the endogenous cannabinoid ligand . In: J. Med. Chem. Volume 39 , no. 22 , 1996, pp. 4515-4519 , doi : 10.1021 / jm960152y .
14. ↑ D. Renck et al .: Design of Novel Potent Inhibitors of Human Uridine Phosphorylase-1: Synthesis, Inhibition Studies, Thermodynamics, and in Vitro Influence on 5-Fluorouracil Cytotoxicity . In: J. Med. Chem. Volume 56 , no. 21 , 2013, p. 8892-8902 , doi : 10.1021 / jm401389u .
15. ↑ A. Jiménez et al .: A Novel Class of Cationic and Non-Peptidic Small Molecules as Hits for the Development of Antimicrobial Agents . In: Molecules . tape 23 , no. 7 , 2018, p. 1513-43 , doi : 10.3390 / molecules23071513 .
16. ↑ Patent GB01472050 : Non-ionic x-ray contrast agents. Registered on November 26, 1975 , published on April 27, 1977 , applicant: SAVAC AG, inventor: NN. ‌
17. ↑ Y. Kameda, N. Asano, M. Yoshikawa, M. Takeuchi, T. Yamaguchi, K. Matsui, S. Horii, H. Fukase: Valiolamine, a new alpha-glucosidase inhibiting aminocyclitol produced by Streptomyces hygroscopicus . In: J. Antibiot (Tokyo) . tape 37 , no. 11 , 1984, pp. 1301-1307 , doi : 10.7164 / antibiotics.37.1301 .
18. ↑ X. Chen, Y. Zheng, Y. Shen: Voglibose (Basen, AO-128), one of the most important alpha-glucosidase inhibitors . In: Curr. Med. Chem. Band 13 , no. 1 , 2006, p. 109-116 , doi : 10.2174 / 092986706789803035 .