Hydroxyproline synthesis

One of the most interesting aspects of ascorbic acid is its role in hydroxyproline synthesis (see Fig. 4-17). Connective tissue grows subcutaneously in polyvinyl sponge implants. Ascorbic acid causes rapid growth of the connective tissue under those conditions, and connective tissue proliferation is associated with a rapid incorporation of hydroxyproline. 

Figure 1. Dynamic utilization of amino acids in pigs. Degradation of essential amino acids via interorgan cooperation results in synthesis of nonessential amino acids. BCAA, branched-chain amino acids D3PG, D-3-phosphoglycerate (cm intermediate of glucose metabolism) HYP, hydroxyproline. Synthesis of serine from its carbon skeleton (D3PG) requires amino acids (e.g. aspartate and glutamate) as donors of the amino group.

Early examples of enantioselective extractions are the resolution of a-aminoalco-hol salts, such as norephedrine, with lipophilic anions (hexafluorophosphate ion) [184-186] by partition between aqueous and lipophilic phases containing esters of tartaric acid [184-188]. Alkyl derivatives of proline and hydroxyproline with cupric ions showed chiral discrimination abilities for the resolution of neutral amino acid enantiomers in n-butanol/water systems [121, 178, 189-192]. On the other hand, chiral crown ethers are classical selectors utilized for enantioseparations, due to their interesting recognition abilities [171, 178]. However, the large number of steps often required for their synthesis [182] and, consequently, their cost as well as their limited loadability makes them not very suitable for preparative purposes. Examples of ligand-exchange [193] or anion-exchange selectors [183] able to discriminate amino acid derivatives have also been described. 

SYNTHESIS AND RU(II)-BINAP REDUCTION OF A KETOESTER DERIVED FROM HYDROXYPROLINE 2(S)-(p tert-BUTOXYCARBONYL-a-(S) and a-(R)-HYDROXYETHYL)-4(R)-HYDROXYPYRROLIDINE-1 -CARBOXYLIC ACID, tert-BUTYL... 

Hydroxyproline-derived polyesters represent a specific embodiment of the synthetic concepts described in Fig. la. The successful synthesis of a hydroxyproline-derived polyester was first reported by Kohn and Langer in 1987 (12). Thereafter, several of these new polyesters were investigated in detail by Yu and Lange (21-23). 

The easy processibility of hydroxyproline-derived polyesters is in marked contrast to the unfavorable material properties of most conventional poly (amino acids) that cannot usually be processed into shaped objects by conventional polymer-processing techniques (7). Furthermore, since the synthesis of poly(N-acylhydroxyproline esters) does not require the expensive N-carboxyanhydrides as monomeric starting materials, poly(N-acylhydroxyproline esters) should be significantly less expensive than derivatives of conventional poly(hy-droxyproline). 

Dashek WV. Synthesis and transport of hydroxyproline-rich components in suspension cultures of sycamore-maple cells. Plant Physiol 1970 46 831-838. 

Sauer A, RobinsonDG. Intracellular localization of posttranslational modifications in the synthesis of hydroxyproline-rich glycoproteins. Peptidyl hydroxylation in maize roots. Planta 1985 164 287-294. 

ENANTIOSELECTIVE SYNTHESIS OF (Z)-N-CARBOBENZYLOXY-3-HYDROXYPROLINE ETHYL ESTER... 

Homochiral hydroxyproline 139 served as the starting material for the synthesis of various bicyclic[5.5]hydantoins 140 (Scheme 19). The corresponding amino derivatives 142 were also available by oxidation of the alcohol 141 and reductive amination of the ketone followed by separation of diastereomers by silica gel column chromatography (Equation 19) <2005BML1161>. 

Hydroxyprolines react as aldehyde equivalents with arylhydrazines in the Fischer indole synthesis to give Al-protected L-tryptophans in moderate to good yields (Scheme 16). The reaction is more suitable for the l series because of the price of the o-Pro starting material (84CPB2126). 

At this stage in our work, Benn and his colleagues ( ) described a synthesis of crotanecine from (2S,4R)-4-hydroxyproline ( ) in which the silyl ether (3 ) is an intermediate. The subsequent reactions are similar to our own projected synthesis, involving both ( ) and (34). 

Ascorbic acid or vitamin C is found in fruits, especially citrus fruits, and in fresh vegetables. Man is one of the few mammals unable to manufacture vitamin C in the liver. It is essential for the formation of collagen as it is a cofactor for the conversion of proline and lysine residues to hydroxyproline and hydroxylysine. It is also a cofactor for carnitine synthesis, for the conversion of folic acid to folinic acid and for the hydroxylation of dopamine to form norepinephrine. Being a lactone with two hydroxyl groups which can be oxidized to two keto groups forming dehydroascorbic acid, ascorbic acid is also an anti-oxidant. By reducing ferric iron to the ferrous state in the stomach, ascorbic acid promotes iron absorption. 

Scheme 25 Synthesis of a Glycosylated Hydroxyproline Building Block Using the Glycosyl Peracetate as a...

It is reported that GPA-1734 inhibits prolyl and lysyl hydroxylations by Fe chelation and that the formation of non-dialyzable labeled hydroxyproline was inhibited 70% at a concentration of 50 pM, yet incorporation of proline into total liver protein was unaffected at this concentration (78BBA(538)328). GPA-1734 is a potent inhibitor of basement membrane synthesis (78MI21002). 

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