3-Hydroxy-2-methylbutyric acid

Fig. 10.25 Mass spectra of the trimethylsilyl derivatives of (a) 3-hydroxy-2-methylbutyric acid, (d) tiglylglycine (mono-TMS), (e) tiglylglycine (di-TMS) and the ethoxime-trimethylsilyl derivatives of (b) 2-methylacetoacetic (peak 1) and (c) 2-methyl-acetoacetic (peak 2) acids.

C2jH3 07 67212-74-2) see Alclometasone dipropionate 2 -hydroxy-4 -(3-methyl-2-butenyloxy)acetophenone (C,3H] 03 24672-83-1) see Sofalcone 2-hydroxy-2-methylbutyric acid ethyl ester (C7H14O3 77-70-3) see Paramethadione 2-hydroxy-2-methylbutyronitrile (Ci H NO 4111-08-4) see Paramethadione 5(R)-(hydroxymethyl)-2-cyclopenten-l(R)-ol (C(jH,(,02 143395-28-2) see Abacavir 2-[l-(hydroxymethyl)cyclopropyl]acctonitrile (QH9NO 152922-71-9) see Montelukast sodium ( )-cis-2-hydroxymethyl-Af,Af-diethyl-l-phenylcyclo-propanecarboxamide... 

Synthesis of (5)-2-Hydroxy-2-methylbutyric Acid by a Chemoenzymatic Methodology... 

Recently, the synthesis of (5)-2-hydroxy-2-methylbutyric acid has been reported using the docking/protecting group concept and HNL from Hevea brasiliensis (ffl>HNL) as catalyst (Scheme 8.1). ... 

Fechter, M.H., Gruber, K., Avi, M., Skranc, W., Schuster, C., Pbchlauer, P., Klepp, K.O. and Griengl, H., Stereoselective biocatalytic synthesis of (S)-2-hydroxy-2-methylbutyric acid via substrate engineering by using thio-disguised precursors and oxynitrilase catalysis. Chem. Eur. J., 2007,13, 3369. 

At high pH (> 10-11) saponification of the sulfonyl chloride to the sodium salt of 3-amino-3-methylbutyric acid-N-sulfonic acid will predominate, and at too low a pH (e.g., pH of 0) hydrolysis to 3-hydroxy-3-methylbutyramide will prevail. 

Carboxylic acids, acyl chlorides, and sulfonyl chlorides used for deri-vatization of 4-aminophenylalanine and >-4-am i n op h e ny I a I a n i n e are as follows 5-hydantoinacetic acid, / ran, v - 4 - co t i n i n ec a r b o xy I i c acid, isonicotinic acid, 3-pyridinepropionic acid, 4-hydroxyphenylacetic acid, 2-butynoic acid, 2-pyrazinecarboxylic acid, cyclopropanecarboxylic acid, 3-hydroxy-2-qui-noxaline carboxylic acid, 5-bromovaleric acid, propargyl chloroformate, 3,4-dimethoxybenzoyl chloride, 2-thiophenesulfonyl chloride, 3-thiophene-carboxylic acid, 2-thiophenecarboxylic acid, 2-methylbutyric acid, 2-thio-pheneacetyl chloride, benzoic acid, furylacrylic acid, 4-nitrophenyl acetic acid, 2,5-dimethoxyphenylacetic acid, p-toluenesulfonyl chloride, 4-(di-methylamino)phenylacetic acid, 3-indolepropionic acid, phenoxyacetic acid, 3-(dimethylamino)benzoic acid, cyclohexanecarboxylic acid, naphtha-lenesulfonyl chloride, 4-bromophenylacetic acid, 4-bromobenzoic acid, 2-phenoxybutyric acid, 3,4-dichlorophenylacetic acid, (l-naphthoxy)acetic acid. 

Viridifloric /3-lactone, 143, has been identified as one of the pheromone components of a complex mixture of volatiles released by the pheromone glands of the male Idea leuconoe butterfly during courtship <1996BMC341>. A racemic mixture of both diastereoisomers was synthesized in four steps from the dilithio salt of 3-methylbutyric acid 144 alkylation with ethanal, dehydration of the secondary alcohol with phosphorus pentoxide, dihydroxylation of the C-C double bond with osmium tetraoxide, and finally formation of the /3-lactone by cyclization with sulfonyl chloride. By comparison with the sample isolated from I. leuconoe, the absolute configuration was established to be (2V,3V)-2-hydroxy-2-(l-methylethyl)-3-butanolide 143. 

A related route to a-hydroxyalkanoic acids is illustrated by the synthesis of / (-)-2-hydroxy-2-methylbutyric acid (407) from (5)(-)-tigloylproline (403). The initial step of halolactonization of 403 with N-bromosuccini-mide in DMF proceeds stereospecifically to give 405 (94.5%) and 407 (5.5%). Debromination of 405 to 409 with tributyltin hydride in benzene, followed by hydrolysis, gave the desired compound 410 (77TL1005 79T2337, 79T2345). 

Aqueous solutions of Cr are generally unstable and undergo rapid disproportionation to Cr and Cr . However Cr complexes with tertiary hydroxy acids such as 2-hydroxy-2-methylbutyric acid and citric acid are stable and permit the preparation and storage of aqueous solutions of Cr compounds. Cr complexes with deuteriated diols have been identified as intermediates in the reaction of CrO " with diols. E.s.r. studies suggest structure (8) for these complexes. With pinacol a similar... 

The plots of the logs/ values (normalized to Gd(III)) for a-hydroxyisobutyric acid HIB), lactate (Lact) for the cation exchange (Dowex 50-WX8) elution (61), and 2-hydroxy-2-methylbutyric acid (HIMBUT) (normalized to La(III)) (62) against the... 

Fig. 13. The plot of log (normalized to La) vs. L giving an Inclined W plot for the 2-hydroxy-2-methylbutyric acid (HIMBUT) (62) at 87 °C. Note that Gd (III) belongs to the heavy lanthanides (third tetrad).

The conclusion was reached that the biosynthetic route was by way of a two-carbon insertion into 2-oxo-3-hydroxy-3-methylbutyric acid (CLXXIV). Taken in conjunction with the established bios3uithesis of valine (CLXXV) from pyruvic acid by way of acetyllactic acid (CLXXVI) and the ketol rearrangement to CLXXIV the biosynthesis of echimidinic acid may be formulated as in Chart VI. 

The structural feature of these compounds is the hexahydronaphthalene ring system which is functionalized with a-methylbutyric acid ester and a P-hydroxy-8-lactone linked by an ethylene bridge. The p-hydroxy-8-lactone portion of these compounds can be easily opened, and it is converted to the 3, 5 -dihydroxyheptanoic acid [22]. This hydroxy acid portion of their structures, which resembles the HMG portion of the HMG-CoA, is responsible for the activity, and it is known to interact competitively with the HMG binding domain of the enzyme active site [37]. 

Chloro-3-hydroxy-3-methylbutyric acid is obtained on addition of aqueous HOC1 to a suspension of 3-methylcrotonic acid (/ ,/ -dimethylacrylic acid).285... 

Hydroxy-2-methylbutyric acid was not a precursor for the tigloyl moieties of (56) and (57), which indicates that introduction of the double bond is by dehydrogenation rather than dehydration. (A parallel feeding experiment was carried out with 2-methylbutyric acid in an attempt to ensure the reliability of this negative result. )... 

In a similar line of research, Forssten et al. [91] investigated the formation of 2-hydroxy-3-methylbutyric acid (ROH) from 2-bromo-3-methylbutyric acid (RBr) at a waterjDCE interface. This 8, 2 reaction in two-phase systems can be represented as... 

Alkaline hydrolysis of germerine yields the alkamine germine, D-(—)-o-methylbutyric acid, [ ]d — 22°, —25 (water), and (-l-)-o-hydroxy-a-methylbutyric acid, m.p. 72-73°, [a]o + 4.4° (water). With baryta at 40° it yields protoveratridine on partial hydrolysis and ultimately germine (19, 51). 

Hydroxy-2-methylbutyric acid, A33.8, A"48 2-Hydroxy-3-methylbutyric acid, A 4.6, A"15... 

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