Supported proline

Proline supports the health of tendons, ligaments, and joints, and works with vitamin C to protect skin and joints. Proline also keeps the heart muscle healthy. 

Proline supported on 1% crosslinked polystyrene (a) Kondo, K., Yamano, T. and Takemoto, K. (1985) Makromolekulare Chemie-Macromolecular Chemistry and Physics, 186, 1781. Proline supported on silica gel column (b) Sakthivel, K., Notz, W., Bui, T. and Barbas, C.F. (2001) Journal of the American Chemical Society, 123, 5260-7. 

Chohamarani and Zamani reported the use of L-proline supported on silica (CAT-20). This methodology provided the Biginelli adducts in good yields (>80%) from aromatic aldehydes. However, the adducts prepared from benzal-dehyde and thiomea gave poor yields (50%, Table 4) [30]. 

Metal ion complexes. These classic CSPs were developed independently by Davankov and Bernauer in the late 1960s. In a typical implementation, copper (II) is complexed with L-proline moieties bound to the surface of a porous polymer support such as a Merrifield resin [28-30]. They only separate well a limited number of racemates such as amino acids, amino alcohols, and hydroxy acids. 

In supported liquid membranes, a chiral liquid is immobilized in the pores of a membrane by capillary and interfacial tension forces. The immobilized film can keep apart two miscible liquids that do not wet the porous membrane. Vaidya et al. [10] reported the effects of membrane type (structure and wettability) on the stability of solvents in the pores of the membrane. Examples of chiral separation by a supported liquid membrane are extraction of chiral ammonium cations by a supported (micro-porous polypropylene film) membrane [11] and the enantiomeric separation of propranolol (2) and bupranolol (3) by a nitrate membrane with a A/ -hexadecyl-L-hydroxy proline carrier [12]. 

Some members of the Liliaceae accumulate free azetidine-2-carboxylic acid in a much higher concentration than that found to be lethal to mung bean seedlings, but it is not incorporated into their proteins. Fowden (43) postulated that these plants either had a proline-incorporating system which was more specific than that found in other species, or some subcellular mechanism operated to prevent the homolog from reaching the sites involved in protein synthesis. Data which supported the first suggestion were subsequently obtained (116). 

Rather scanty evidence exists for the participation of free radicals in Alzheimer s disease and Down s syndrome. However, more recendy, reports have appeared that suggest possible free-radical involvement in the pathogenesis of these two conditions. Zemlan et al. (1989) repotted that the activity of the free-radical scavenging enzyme, SOD, was significantly increased in fibroblast cell lines derived from familial Alzheimer s and Down s patients. They hypothesized that the elevation in SOD activity observed in the Alzheimer patients supports the theory that paired helical filaments are formed by free-radical hydroxylation of proline residues. They further su ested that SOD levels might also be increased in the brains of Alzheimer s and Down s patients, and that the increase in SOD may reflect an enhanced generation of free radicals. 

Gruttadauria, M., Giacalone, F. and Noto, R. (2008) Supported proline and proline-derivatives as recyclable organocatalysts. Chemical Society Reviews, 37 (8), 1666-1688. 

In 2001, Sarko and coworkers disclosed the synthesis of an 800-membered solution-phase library of substituted prolines based on multicomponent chemistry (Scheme 6.187) [349]. The process involved microwave irradiation of an a-amino ester with 1.1 equivalents of an aldehyde in 1,2-dichloroethane or N,N-dimethyl-formamide at 180 °C for 2 min. After cooling, 0.8 equivalents of a maleimide dipo-larophile was added to the solution of the imine, and the mixture was subjected to microwave irradiation at 180 °C for a further 5 min. This produced the desired products in good yields and purities, as determined by HPLC, after scavenging excess aldehyde with polymer-supported sulfonylhydrazide resin. Analysis of each compound by LC-MS verified its purity and identity, thus indicating that a high quality library had been produced. 

Recently, a novel method for the synthesis of a library of substituted prolines with microwave technology [95] has been described. In the first step, 1 equivalent of an amine is added to 1.1 equivalents of an aldehyde in 1,2-dichloroethane (DCE), with subsequent irradiation at 180 °C for 2 min. In the second step, 0.85 equivalents of the maleimide are added and the resulting solution is heated at 180 °C for an additional 5 min. This methodology allowed the production of a solution-phase library of 800 compounds with a crude purity between 65 and 82% (Scheme 9.45). The compounds were purified by solid-supported reagent scavenging to afford the final products with a purity between 90 and 98% and in 79-85 % yield [96]. 

For example, a proline-based chiral ligand was attached to a vinyl-substituted monomer (Fig. 42.15) by reacting vinylbenzoyl chloride with the amine functionality of the ligand [106]. As mentioned previously, the apolar Merrifield resin as a support is not swollen in polar solvents. Hence, in order to match the polarity of the resin with that of the typically used substrates in enantioselective hydrogenation, the functionalized monomer was copolymerized with polar units of methacrylic acid 2-hydroxyethyl ester. 

Although no experiment has yet been reported to support the idea, it seems clear that a majority of the pyrrolidine alkaloids arise from the ornithine, pu-trescine, and proline pool. This could be the case for ficine (61) and isoficine (62), vochysine (63), and phyllospadine (64) but also of the Darlingia alkaloids, which share common features with hygrine this assertion probably also holds for the ruspolinone (25) and odorine-roxburghlin (59) families. Peripentadenine, isolated from a plant of the family Elaeocarpaceae, bears resemblance to other alkaloids of the elaeocarpus type such as isoelaeocarpicine (124) (161). It cannot be excluded, however, that spermidine may be a biosynthetic intermediate instead of putrescine. The question of the origin of ant alkaloid substances remains so far without an obvious answer. 

Once it is part of a cyclic dipeptide, the prolyl residue becomes susceptible to enantiomerization by base (see Section 7.22). The implication of the tendency of dipeptide esters to form piperazine-2,5-diones is that their amino groups cannot be left unprotonated for any length of time. The problem arises during neutralization after acidolysis of a Boc-dipeptide ester and after removal of an Fmoc group from an Fmoc-dipeptide ester by piperidine or other secondary amine. The problem is so severe with proline that a synthesis involving deprotection of Fmoc-Lys(Z)-Pro-OBzl produced only the cyclic dipeptide and no linear tripeptide. The problem surfaces in solid-phase synthesis after incorporation of the second residue of a chain that is bound to the support by a benzyl-ester type linkage. There is also the added difficulty that hydroxymethyl groups are liberated, and they can be the source of other side reactions. 

To support the proposed hydride transfer as shown for the substrate geranylacetone 68 in Fig. 30 proline was linked to the primary face of P-CD yielding the tertiary amine 101 which was complexed with ruthenium and employed to ATH under standard conditions. No product was formed at all which is in good agreement with observations by other groups (31,49,50). The presence of a hydrogen... 

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