Methyl acetolactate

Methyl acetolactate, A33 Methyl angolensate, T52 0-methylanhalonidine, K2 a-methylaspartic acid, A40... 

Carbomethoxybutyric acid, A34.8 2-Methylglutaric acid, A32.12 Methyl acetolactate, A33.2... 

There are several commercially available sulfonylurea herbicides that contain a 2-pyrimidine group <2006H(68)561>. These compounds, which function by inhibition of acetolactate synthase (ALS), an enzyme involved in the early stage of branched-chain amino acid synthesis, include sulfometuron-methyl 1095, primisulfuron-methyl 1096, chlorimuron-ethyl 1097, bensulfuron-methyl 1098, ethoxysulfuron 1099, nicosulfuron 1100, and pyrazosulfuron-ethyl 1101. Related nonsulfonylureas include the sulfide pyrftalid 1102 and the ether pyriminobac-methyl 1103. 

The third type of carbon-branched unit is 2-oxoisovalerate, from which valine is formed by transamination. The starting units are two molecules of pyruvate which combine in a thiamin diphosphate-dependent a condensation with decarboxylation. The resulting a-acetolactate contains a branched chain but is quite unsuitable for formation of an a amino acid. A rearrangement moves the methyl group to the (3 position (Fig. 24-17), and elimination of water from the diol forms the enol of the desired a-oxo acid (Fig. 17-19). The precursor of isoleucine is formed in an analogous way by condensation, with decarboxylation of one molecule of pyruvate with one of 2-oxobutyrate. 

In a different application, the reactivity of the condensing decarboxylase acetolactate synthetase was modeled (equation 7). C2a-hydroxyethylbenzothiazole was converted to its silyl ether, that on treatment with BuLi and methylpyruvate afforded the acetolactyl adduct, whose desilylation, followed by iV-alkylation, then treatment with Et3N in MeOH gave the methyl ester of acetolactate, along with some 2-acetylbenzothiazoline side product59. 

One of the most effective classes of herbicide are the sulfonylureas. They are applied in quantities of no more than a few grams per hectare. The action of sulfonylureas is based on inhibition of acetolactate synthase (ALS) [9]. The fluorine-containing derivative Primsulfuron methyl has selectivity in the cultivation of maize [10]. 

Lolium biotypes exist which have resistance to the sulfonylurea herbicides chlorsulfuron and metsulfuron methyl (4). The biotype used in the studies presented here is resistant to both these sulfonylurea herbicides. Sulfonylurea herbicides inhibit the chloroplastic enzyme acetolactate synthase (ALS), also known as acetohydroxyacid synthase (AHAS) (16). Inhibition of this enzyme results in disruption of the synthesis of the branched-chain amino acids valine and isoleucine (161. The imidazolinone herbicides also inhibit ALS Q2). In some species auxins can protect against chlorsulfuron inhibition (S. Frear, USDA North Dakota, personal communication) the mechanistic basis for this protection is not known. We have measured the ALS activity in the resistant and susceptible Lolium and have also checked for any induction of ALS activity following treatment with the sulfonylurea herbicide chlorsulfuron. 

The reduction step catalyzed by this enzyme has been shown to use the 4-pro-S hydrogen of NADPH (195), and when C-labeled a-acetolactate 217 was used, it could be shown that the migrating methyl group eventually became the 2-pro-S methyl group of valine 179. The migration thus has the... 

Sulfometuron methyl Branched Chain Acetolactate synthase... 

Fio. 7. Scheme of biosynthesis of valine and isoleucine. R tepresents a methyl group in valine and an ethyl group in isoleucine biosynthesis. I is pyruvate or a-keto-butyrate II is a-acetolactate or a-aceto-a-hydroxybutyrate HI is a-keto-/3-hydroxy> isovalerate or a-keto- -hydroxy- S-metbylvalerate IV is a,/ -dihydroxyisovalerate or a-0-dihydroxy- -methylvalerate V is a-ketoisovalerate or a-keto-d-methylvalerate and VI is valine or isoleucine. 

Strassman et al. (144), on the basis of the equal incorporation of lactate C-2 into valine C-2 and C-3, suggested that valine synthesis was initiated by the condensation of two pyruvate molecules, similar to the known condensation of pyruvate and acetaldehyde to yield acetolactic acid (162). The methyl group of pyruvate was indicated to be the precursor of the valine methyl groups. To explain this required a migration of the methyl group as in the pinacol rearrangement. 

Following the ketol condensation to yield a-acetolactate and a-aceto-a-hydroxybutyrate the question arises as to whether the pinacol rearrangement occurs first to form a-keto-jS-hydroxyisovaleric acid and a-keto-i9-hydroxy- 8-methylvaleric acid (Fig. 7, III), or whether there is prior reduction. The evidence favoring pinacol rearrangement followed by reduction of the a-keto- 3-hydroxy acids is that enzymes have been found in Neurospora and E. coli which catalyze the reduction of synthetically prepared a-keto-(8-hydroxyisovaleric acid and a-keto-j8-hydroxy-/3-methyl-valeric acid to the corresponding a,/8-dihydroxy acids (166, 167). 

Acetolactate synthase (ALS) is the enzyme target site of the sulfonyl-ureas. In common with the imidazolinone aryl carboxylates, these herbicides inhibit valine and isoleucine biosynthesis. The imidazolinones are exemplified by Assert (8), which consists of a mixture of m- and p-isomers. The selectivity of ALS inhibitors invariably can be accounted for by differential metabolism or uptake or related phenomena rather than by any significant inherent difference in the properties of the ALS enzymes of crop and weed species. Assert is another example of a herbicide activated in plants by deesterification to the phytotoxic acid, and susceptible species such as Avena fatua (wild oat) are unable to metabolize the molecule further. Facile ring-methyl hydroxylation to the m- and p-benzyl alcohols, however, followed by glycosylation confers tolerance to maize and wheat." ... 

Acetolactic acid, methyl ester, A33 Acetylaranotin, Y21 Acetylchloromalic acid, A1 Achillene, T1 Achillin, T22 Achromycin, Y28 Aconitine, K33 Acoradienes, T29, T5 Acoragermacrone, T22 Acorenols, T29 Acenaphthenes, A35 ... 

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