Rearrangement amino acid precursors

V-acylaziridine-2-imides to oxazoline-4-imides, followed by hydrolysis of these latter compounds, has been used586 to afford chiral / -hydroxy-a-amino acid precursors. It has been suggested587 that the observed thermal rearrangement of c/.s-aziridinyl ketone tosylhydrazones (449) to 5-alkylamino-3,5-diphenyl-l-tosyl-2-pyrazolines (450) is... 

Simple" ketones can be used as amino acid precursors. In very early work, Noyes convened camphor (7.144) to 7.145. Schmidt rearrangement led to the formation of 3-amino-1,2,2-trimethylcyclopentane carboxylic acid, 7.146. A... 

Main Rearrangements of BENA In previous Sections (3.5.4.1. and 3.5.4.2.), a-hydroxy oximes (503) and their bis-silyl derivatives (504) were considered as undesired by-products, formed in the synthesis and chemical transformations of BENA. The aim was to minimize the amount of these impurities. On the other hand, oximes (503) are convenient precursors of various useful products, such as p-amino alcohols (530), amino acids (531), a-hydroxycarbonyl compounds (532) and various heterocyclic systems (533). 

A potential versatile route into a-amino acids and their derivatives is via a combination of (i) nitrile hydratase/amidase-mediated conversion of substituted malo-nonitriles to the corresponding amide/acid followed by (ii) stereospecific Hofmann rearrangement of the amide group to the corresponding amine. Using a series of a,a-disubstituted malononitriles 14, cyanocarboxamides 15 and bis-carboxamides 16, the substrate specificity of the nitrile hydratase and amidase from Rhodococcus rhodochrous IF015564 was initially examined (Scheme 2.7). The amidase hydrolyzed the diamide 16 to produce (R)-17 with 95% conversion and 98%e.e. Amide 17 was then chemically converted to a precursor of (S)-a-methyldopa. It was found... 

The incorporation of these artificial structural elements as well as the subsequent cycliza-tions are generally performed according to standard procedures e.g. in the case of 5-aminopentanoic acid (1, n = 3) and 6-aminohexanoic add (1, n=4) the cyclization proceeds in good yields without particular difficulties. 35 Conversely, real turn mimetics may increase cyclization yields as a result of the anticipated rearrangement of the linear precursors. t28-87-481-482 in most cases, the nonnatural amino adds or equivalent building blocks are used in the synthetic steps in complete analogy to natural amino acids. 

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. 

The known intermediates and reactions, considered above, indicate that the conversion of shikimic acid to the aromatic amino acids takes place without rearrangement of the carbon atoms of the ring. Some studies of the incorporation of labeled precursors into the aromatic amino acids have been entirely in accord with this conclusion other studies have not. This discrepancy has been briefly reviewed, but not resolved. 

Very few syntheses of tetrazoles were reported in 2003. Various a-dialkylated (3-keto esters 219 underwent Schmidt rearrangement with trimethylsilyl azide to give tetrazole 220, which could be elaborated further to azido acid 221, precursors to a-dialkylated a-amino acids <03TL3179>. Di(benzotriazolyl)methanimine 222 reacted with various secondary amines to generate 223, which when treated with sodium azide in the presence of acetic acid yielded N,N-disubstituted 5-aminotetrazoles 224 in moderate to good yields <03JOC4941>. 

A novel neuroexcitotoxic amino acid, (-)-dysiherbaine, was synthesized starting from a carbohydrate precursor in the laboratory of M. Sasaki.Under benzylation conditions, the cyclic 2,3-epoxy alcohol underwent a facile Payne rearrangement and the rearranged alkoxide was trapped with benzyl bromide. 

Terpenoids do not necessarily contain exact multiples of five carbons and allowance has to be made for the loss or addition of one or more fragments and possible molecular rearrangements during biosynthesis. In reality the terpenoids are biosynthesized from acetate units derived from the primary metabolism of fatty acids, carbohydrates and some amino acids (see Fig. 2.10). Acetate has been shown to be the sole primary precursor of the terpenoid cholesterol. The major route for terpenoid biosynthesis, the mevalonate pathway, is summarized in Fig. 2.16. Acetyl-CoA is involved in the generation of the C6 mevalonate unit, a process that involves reduction by NADPH. Subsequent decarboxylation during phosphorylation (i.e. addition of phosphate) in the presence of ATP yields the fundamental isoprenoid unit, isopentenyl pyrophosphate (IPP), from which the terpenoids are synthesized by enzymatic condensation reactions. Recently, an alternative pathway has been discovered for the formation of IPP in various eubacteria and plants, which involves the condensation of glyceraldehyde 3-phosphate and pyruvate to form the intermediate 1-deoxy-D-xylulose 5-phosphate (Fig. 2.16 e.g. Eisenreich et al. 1998). We consider some of the more common examples of the main classes of terpenoids below. 

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