L- -y-Amino-a-hydroxybutyric acid

Dantrolene sodium L-(-) - y-Amino-a-hydroxybutyric acid Amikacin... 

Preparation of L-(-)-y-benzyloxycarbonylamino-a-hydroxybutyric acid L-(-)-y-amino-a-hydroxybutyric acid (7.4 g, 0.062 mol) was added to a solution of 5.2 grams (0.13 mol) of sodium hydroxide in 50 ml of water. To the stirred solution was added dropwise at 0-5°C over a period of 0.5 hour, 11.7 grams (0.068 mol) of carbobenzoxy chloride and the mixture was stirred for another hour at the same temperature. The reaction mixture was washed with 50 ml of ether, adjusted to pH 2 with dilute hydrochloric acid and extracted with four 80 ml portions of ether. The ethereal extracts were combined, washed with a small amount of saturated sodium chloride solution, dried with anhydrous sodium sulfate and filtered. The filtrate was evaporated in vacuum and the resulting residue was crystallized from benzene to give 11.6 grams (74%) of colorless plates MP 78.5°C to 79.5°C. 

Hydroxy-a-amino-acids are available by reduction and hydrolysis of the corresponding jS-keto-esters, obtained from methyl isocyanoacetate and acyl halides via oxazole-4-carboxylate intermediates. ° A synthesis of L-y-amino-/3-hydroxybutyric acid has been reported in which the key step is a dehydration of L-a-hydroxysuccinamic acid to the corresponding y-cyano-acid, presumably via a y-iminobutyrolactone. ° This could prove to be a general route to (3- and y-cyano-carboxylic acids. 

Ascorbic acid is involved in carnitine biosynthesis. Carnitine (y-amino-P-hydroxybutyric acid, trimethylbetaine) (30) is a component of heart muscle, skeletal tissue, Uver and other tissues. It is involved in the transport of fatty acids into mitochondria, where they are oxidized to provide energy for the ceU and animal. It is synthesized in animals from lysine and methionine by two hydroxylases, both containing ferrous iron and L-ascorbic acid. Ascorbic acid donates electrons to the enzymes involved in the metabohsm of L-tyrosine, cholesterol, and histamine (128). 

Carnitine, L-3-hydroxy-4-(trimethylammonium)butyrate, is a water-soluble, tri-methylammonium derivative of y-amino-jS-hydroxybutyric acid, which is formed from trimethyllysine via y-butyrobetaine [40]. About 75% of carnitine is obtained from dietary intake of meat, fish, and dairy products containing proteins with trimethyllysine residues. Under normal conditions, endogenous synthesis from lysine and methionine plays a minor role, but can be stimulated by a diet low in carnitine. Carnitine is not further metabolized and is excreted in urine and bile as free carnitine or as conjugated carnitine esters [1, 41, 42]. Adequate intracellular levels of carnitine are therefore maintained by mechanisms that modulate dietary intake, endogenous synthesis, reabsorption, and cellular uptake. 

Asymmetric epoxidation of homoallylic alcohols. Sharpless asymmetric epoxidation of primary homoallylic alcohols with l-( + )-diethyl tartrate proceeds with only moderate enantiomeric selectivity (23-55% ee) and opposite to that observed with allylic alcohols. Unfortunately, operation at low temperatures to improve the enantiomeric excess also retards the rate drastically. Even so, this epoxidation provides a useful synthesis of (-l-)--y-amino-P(R)-hydroxybutyric acid (1). 

A soln. of N-tosyl-L-methionine in a mixture of methyl iodide, acetic acid, and 8Q% formic acid allowed to stand 10 hrs. at room temp, in the dark, coned, below 40° under reduced pressure, the resulting oil triturated with dry ether, dissolved in N NaOH-soln., stirred and heated 3 hrs. at 90°, while the pH is kept at 6-7 by addition of more N NaOH, and the intermediate N-tosyl-a-amino-7-hydroxybutyric acid treated with N HCl at pH 2-3 -> N-tosyl-a-amino-y-butyro-lactone. Y 92%. F. e. s. H. Sugano and M. Miyoshi, Bull. Chem. Soc. Japan 46, 669 (1973). 

M. E. Jung and T. Shaw, Total synthesis of (R)-glycerol acetonide and the antiepileptic and hypotensive drug (-)-y-amino-/l-hydroxybutyric acid (GABOB) use of vitamin C as a chiral starting material, J. Am. Chem. Soc., 102 (1980) 6304-6313. 

---