Proline precursor

However, following its formation, the semialdehyde undergoes a spontaneous cyclization and is converted to a A -pyrroline-5-carboxylic acid (P5C), a proline precursor. 

Asymmetric hydrocarboxylation may be applied to the synthesis of chiral A -protected amino carboxylic acids, pyrrolidones or proline precursors. With this synthetic target in mind hydrocarboxylation of/f-substituted A -vinyl- and A -allylphthalimides is catalyzed with palla-dium(ll) chloride in the presence of the chiral phosphanes Diop or DIOCOL28. Although high product selectivities and regioselectivities are achieved, only very low asymmetric inductions are observed (up to 4% ee)28. Until now the best results in a vinyl imide hydrocarboxylation are achieved with, V-vinylsuccinimide in the presence of palladium(II) chloride and (-)-Diop with a 17.1 % ee12. 

A review of approaches to the design and synthesis of azabicycloalkane amino acids as constrained dipeptide mimetics has been reported. These approaches include 7-membered lactam ring formation by free radical cyclization from a substituted proline precursor <04SL1449>. 

Proline Hydroxyproline Proline precursor Hepatocyte DNA, protein synthesis ketoglutarate)... 

Hydroxy-L-prolin is converted into a 2-methoxypyrrolidine. This can be used as a valuable chiral building block to prepare optically active 2-substituted pyrrolidines (2-allyl, 2-cyano, 2-phosphono) with different nucleophiles and employing TiQ as Lewis acid (Eq. 21) [286]. Using these latent A -acylimmonium cations (Eq. 22) [287] (Table 9, No. 31), 2-(pyrimidin-l-yl)-2-amino acids [288], and 5-fluorouracil derivatives [289] have been prepared. For the synthesis of p-lactams a 4-acetoxyazetidinone, prepared by non-Kolbe electrolysis of the corresponding 4-carboxy derivative (Eq. 23) [290], proved to be a valuable intermediate. 0-Benzoylated a-hydroxyacetic acids are decarboxylated in methanol to mixed acylals [291]. By reaction of the intermediate cation, with the carboxylic acid used as precursor, esters are obtained in acetonitrile (Eq. 24) [292] and surprisingly also in methanol as solvent (Table 9, No. 32). Hydroxy compounds are formed by decarboxylation in water or in dimethyl sulfoxide (Table 9, Nos. 34, 35). 

A number of iron-containing, ascorbate-requiring hydroxylases share a common reaction mechanism in which hydroxylation of the substrate is linked to decarboxylation of a-ketoglutarate (Figure 28-11). Many of these enzymes are involved in the modification of precursor proteins. Proline and lysine hydroxylases are required for the postsynthetic modification of procollagen to collagen, and prohne hydroxylase is also required in formation of osteocalcin and the Clq component of complement. Aspartate P-hydroxylase is required for the postsynthetic modification of the precursor of protein C, the vitamin K-dependent protease which hydrolyzes activated factor V in the blood clotting cascade. TrimethyUysine and y-butyrobetaine hydroxylases are required for the synthesis of carnitine. 

Evidence exists that the relative solubility of amines and inhibitors in heterogeneous oil-water systems could be decisive in formation of nitrosamines and blocking these reactions, Nitrosopyrrolidine formation in bacon predominates in the adipose tissue despite the fact that its precursor, proline, predominates in the lean tissue (5,6,7). Mottram and Patterson (8) partly attribute this phenomenon to the fact that the adipose tissue furnishes a medium in which nitrosation is favored, Massey, et al, (9) found that the presence of decane in a model heterogeneous system caused a 20-fold increase in rate of nitrosamine formation from lipophilic dihexylamine, but had no effect on nitrosation of hydrophilic pyrrolidine. Ascorbic acid in the presence of decane enhanced the synthesis of nitrosamines from lipophilic amines, but had no effect on nitrosation of pyrrolidine. The oil-soluble inhibitor ascorbyl palmitate had little influence on the formation of nitrosamines in the presence or absence of decane. 

Mechanism of NPYR Formation The consistent occurrence of NPYR in fried bacon and cooked-out fat has led to an intensive search for both the precursors and mechanism that could account for its formation. Although model system studies have implicated a number of compounds including proline, collagen, putreseine, spermidine, pyrrolidine and glycyl-L-glycine as possible... 

How proline is converted to NPYR has not yet been fully elucidated and could conceivably occur by either of two pathways (29, ). One pathway involves the initial N-nitrosation of proline, followed by decarboxylation, while in the other, proline is first decarboxylated to pyrrolidine followed by N-nitrosation to NPYR. Since the conversion of N-nitrosoproline (NPRO) to NPYR occurs at a much lower temperature than the transformation of proline to pyrrolidine, the pathway involving intermediacy of NPRO is thus the more likely route ( ). It has been reported that preformed NPRO in raw bacon is not the primary precursor of NPYR in cooked bacon (29,33-5), as shown by the fact that ascorbyl paImitate, when added to bacon, inhibits the formation of NPYR (33). However, this by no means rules out the intermediacy of NPRO which could be formed at the higher temperatures attained during the frying process (29,36). 

A rich family of diazaphospholes 260-262 having hcxahydro- l//-pyrrolo [l,2-c][l, 3, 2]diazaphosphole backbone was readily prepared by the reaction of phenylphosphorodichloridite or another P(III) precursor with anilides of (iS )-proline, (S)-pyroglutamic acid, and (S)-indoline carboxylic acid in high yields diastereoselectively [95],... 

Functionalized 5,6-dihydro-4// -oxazines are direct precursors of a series of useful products, for example, of proline derivatives (539), unnatural amino acids (540), and some alkaloids (541). 

The reaction of the aldehyde 256 with proline gave a product which was not the expected dihydiodibenz[r,f ]azepinc 257. Spectroscopic analysis revealed that this new product was an oxazolidine 259 (obtained as a single isomer) resulting from the 1,3-cycloaddition of the azomethine ylide 258 to the precursor aldehyde 256 (Scheme 38) <1999J(P1)2605>. 

Arginine Arginine is a precursor for a number of compounds, including proline and nitric oxide. Nitric oxide is a signalling molecule, proline is needed for formation of collagen, some of which is needed for provision of new tissue. Arginine has been shown to be benehcial for the healing of wounds and for this reason is included in some parenteral feeds (Table 18.4). 

This zinc-dependent enzyme [EC 3.4.17.1], a member of the peptidase family M14, catalyzes the hydrolysis of peptide bonds at the C-terminus of polypeptides. Little hydrolytic action occurs if the C-terminal amino acid is aspartate, glutamate, arginine, lysine, or proline. Car-boxypeptidase A is formed from a precursor protein, procarboxypeptidase A. 

The hydroxylation of specific Pro residues in procollagen, the precursor of collagen, requires the action of the enzyme prolyl 4-hydroxylase. This enzyme (Mt 240,000) is an a2/32 tetramer in all vertebrate sources. The proline-hydroxylating activity is found in the a subunits. (Researchers were surprised to find that the )3 subunits are identical to the enzyme protein disulfide isomerase (PDI p. 152) these subunits do not participate in the prolyl hydroxylation activity.) Each a subunit contains one atom of nonheme iron (Fe2+), and the enzyme is one of a class of hydroxylases that require a-ketoglutarate in their reactions. 

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