A-aminooxy acids

The repulsion of the lone pair electrons of nitrogen and oxygen atoms in the N-O bond in a-aminooxy acid derivatives is expected to give strong pre-organization at the monomeric level. This correlates with the finding that intramolecular H-... 

Shin I, Lee J, Facile Synthesis of N- and O-Glycosylated a-Aminooxy Acids as Building Blocks for the Structural Studies of Glycosylated Pseudopeptides, Synlett., 9 1297, 2000. 

Aminooxy peptides, correlates of/S-peptides composed of a-aminooxy acids as analogues of iS-amino acids with replacement of by an oxygen atom. The lone pair repulsion of the nitrogen and oxygen atoms renders the backbone of aminooxy peptides more rigid than that of /S-peptides [X. Li, Chem. Commun. 2006, 3367]. 

The inhibition data for the aminooxy acids was treated similarly (Table I). For the series of aminooxy acids ranging from the acetate to the valerate, and for gabaculine, there was little change in kcat (range from 0.11 to 0.18 sec ) whereas there was a 210-fold range of values of K[Pg.130]

The inhibitory potencies of the compounds, along with those of several GAD inhibitors from the literature, are summarized in Table II. Reasonable agreement was found between the bacterial and insect enzymes. Toxic compounds were good inhibitors of GAD, in general, although aminooxy acids 1 and 2 (Table II) were potent inhibitors without being very toxic. A previous observation that insect GAD is not inhibited by aminooxyacetate (15) may be explained by the use of different enzyme preparations in the two studies. In the present work it was found that GAD in a crude muscle homogenate was not consistently inhibited by aminooxyacetate. It was this observation that led to the above purification protocol. 

Figure 9. PAL inhibitors, a-aminooxy- -phenylpropionic acid (AOPP) and amino-...

D-phenylalanine, the sterioisomer of the naturally occurring L-phenylalanine, inhibits the PAL activity. Szkutnicka and Lewak (18) found that the application of this compound to germinating seeds caused an increase in the PAL level. They attributed this to the decrease in the production of cinnamic acid and compounds derived therefrom. Similar results have been obtained by Amrhein and Gerhardt (19) with the PAL-inhibitors, L-a-aminooxy-8-phenylpropionic acid and a-aminooxyacetic acid on gherkin seedlings. They found that the synthesis of hydroxycinnamic acids was inhibited and that the PAL level increased. This increase was suppressed when tr<2 s-cinnamic acid was applied. 

Fig. 1. The structures of a-aminooxy acetic acid(AOA) and a-aminooxy-B-phenyl-propionic acid (AOPP)...

Amrhein, N., and K.H. Godeke (1977). a-Aminooxy-B-phenyl-propionic acid - a potent inhibitor of L-phenylala-nine ammonia-lyase in vitro and in vivo. Plant Sci. Lett.. 8, 313-317. 

In this chapter, the discussion will concentrate on two inhibitors with a reasonable claim to selective action on enz3ones related to the shikimate pathway glyphosate, which inhibits 5-enolpyruvylshikimate 3-phosphate (EPSP) synthase and L-a-aminooxy-3 phenylpropionic acid (L-AOPP), an inhibitor of phenylalanine ammonia-lyase (PAL) (Fig. 2). In addition to introducing a novel inhibitor of PAL, (R)-(l-amino-2-phenylethyl)phosphonic acid (APEP), previous and current efforts to design inhibitors of other shikimate pathway enzymes will be described. The treatment presented here will show that the deductions and predictions made on the basis of the abstract scheme in Figure 1 can be, and have been, tested on the basis of the real pathway presented in Figure 2. 

Fig. 9. Structures of phenylalanine (1 ) and of phenylalanine analogs discussed in the text. ( ), 5-(l-amino-2-phenylethyl)tetrazole ( ), (1-amino-2-phenylethy1) phosphonic acid ( ), (l-amino-2-phenylethyl)phosphonous acid ( ), a-aminooxy-8-phenylpropionic acid ( ), a-hydrazino-6-phenylpropionic acid (7 ), 3-methylene-phenylalanine (S), (1,4-cyclohexadienyl)-alanine ( ), o-carboranylalanine (10), adamantylalanine.

L-phenylalanine, L-a-aminooxy-g-phenylpropionic acid (AOPP, in Fig. 9) should have an increased inhibitory ability. This was confirmed beyond our expectations, as L-AOPP inhibited buckwheat PAL with a Ki of 1.4 nM (Table 2) and also inhibited the biosynthesis of phenylpropanoid compounds in vivo without deleterious effects on normal plant development. Selective accumulation of phenylalanine in... 

L-a-aminooxy-3-phenylpropionic acid D-a-aminooxy-3-phenylpropionic acid L-a-hydrazino-3 phenylpropionic acid D-a-hydrazino-3 phenylpropionic acid... 

Inhibition of lignin formation by L-a-aminooxy-8-phenylpropionic acid, an inhibitor of phenylalanine ammonia-lyase. Eur. J. Cell Biol. 29 139-144. 

Hydroxamic acids are an important class of compounds targeted as potential therapeutic agents. A-Fmoc-aminooxy-2-chlorotrityl polystyrene resin 61 allowed the synthesis and subsequent cleavage under mild conditions of both peptidyl and small molecule hydroxamic acids (Fig. 14) [70]. An alternative hydroxylamine linkage 62 was prepared from trityl chloride resin and tV-hydroxyphthalimide followed by treatment with hydrazine at room temperature (Scheme 30) [71]. A series of hydroxamic acids were prepared by the addition of substituted succinic anhydrides to the resin followed by coupling with a variety of amines, and cleavage with HCOOH-THF(l 3). 

Mellor SL, McGuire C, Chan WC. lV-Fmoc-aminooxy-2-chlorotrityl polystyrene resin A facile solid-phase methodology for the synthesis of hydroxamic acids. Tetrahedron Lett 1997 38 3311-3314. 

In conclusion, we anticipate that A-Fmoc-aminooxy-2-chlorotrityl polystyrene will prove an indispensable reagent for the solid-phase synthesis of hydroxamic acids by multiple and combinatorial approaches. Not only is its production both efficient and cost effective, but release of the assembled hydroxamic acid derivative is readily accomplished using mild acidolytic reagents. 

The first resolution of [6]-helicene was achieved by Newman and Lednicer 78) by crystallization with the aid of a chiral complexing agent, 2-(2,4,5,7-tetranitro-9-fluorenylidene aminooxy)propionic acid (TAPA), which was especially designed for this purpose. (R)- and (S)-TAPA (79 a) form diastereomeric charge-transfer (CT) complexes with the enantiomers of hexahelicene. Several other helicenes could also be resolved using this reagent. 

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