Prolines compounds

Ramstad proposed a ring closure of a linear tetrapeptide to Agurell s compound 67 which could either epimerize irreversibly to the d-proline compound 18 or undergo oxidative ring closure to the peptide alkaloids as also proposed by Agurell. Any of the observations reported... 

More recently, 5-hydroxy and 5-fluoro derivatives of the 3,5-methanoproline (26) were analyzed comparatively as N-acetyl methyl esters (Fig. 11.7) by NMR and in the crystalline state for their preferred conformations [90]. In 3,5-methanoproline both pyrrolidine ring puckers are incorporated into the same framework (Fig. 11.7), which allows the dissection of the relative contributions of ring pucker and inductive effects to the conformation of the proline compounds. The hydroxy... 

The introduction of iV-substituents in aminoborneols is also possible by lithium aluminum hydride reduction of amides formed with activated carboxylic acids44, e.g., (S)-iV-(benzyloxy-carbony])proline. Compounds of this type 39-41 have been used as catalysts in the enantiose-lective addition of zinc alkyls to carbonyl compounds (Section D. 1.3.1.4.). 

J., Munger, J.D Jr. Mavinahalli, J., and Sheldon, R. (2008) Biocatalytic process for the preparation of substantially steromerically pure fused bicyclic proline compounds. Patent WO/2010/008828, filed June 24, 2008 and issued Jan. 21, 2010. 

Finally, the hydrogel supramolecular structure, formed from L-proline compound 210 (Fig. 4.45) was tested as catalyst (20 mol%) at in the enantiose-... 

A large number of amino-methylsubstituents were introduced by the Mannich reaction which works as smoothly with the lesorcinarene 1 as it had been reported for calixaienes [25]. From the eight aminoderivatives thus prepared and investigated [22] we restrict ourselves here to the L-proline compound 4 which was obtained without any racemization. The system can adopt four different protonation states (Scheme 11) which were all characterized. Computer-aided potentiometric titrations yielded the relevant pK values with an average error of +0.2 units, with excellent fits assuming the same value for the different independently treated phenyl units in the macrocycle. H-NMR titrations allowed the different steps as shown in Scheme 12 to be identified. Due to the betaine formation the pK of the... 

Proline m which the a ammo group is secondary gives an orange compound on reac tion with nmhydnn... 

The most successful of the Lewis acid catalysts are oxazaborolidines prepared from chiral amino alcohols and boranes. These compounds lead to enantioselective reduction of acetophenone by an external reductant, usually diborane. The chiral environment established in the complex leads to facial selectivity. The most widely known example of these reagents is derived from the amino acid proline. Several other examples of this type of reagent have been developed, and these will be discussed more completely in Section 5.2 of part B. 

Proline, in which the a-fflnino group is secondary, gives an orange compound on reaction with ninhydrin. 

A -Pyrroline has been prepared in low yield by oxidation of proline with sodium hypochlorite (71), persulfate (102), and periodate (103). A -Pyrroline and A -piperideine are products of enzymic oxidation via deamination of putrescine and cadaverine or ornithine and lysine, respectively (104,105). This process plays an important part in metabolism and in the biosynthesis of various heterocyclic compounds, especially of alkaloids. 

Since the proline residue in peptides facilitates the cyclization, 3 sublibraries each containing 324 compounds were prepared with proline in each randomized position. Resolutions of 1.05 and 2.06 were observed for the CE separation of racemic DNP-glutamic acid using peptides with proline located on the first and second random position, while the peptide mixture with proline preceding the (i-alamine residue did not exhibit any enantioselectivity. Since the c(Arg-Lys-0-Pro-0-(i-Ala) library afforded the best separation, the next deconvolution was aimed at defining the best amino acid at position 3. A rigorous deconvolution process would have required the preparation of 18 libraries with each amino acid residue at this position. 

The feasibility of this approach was demonstrated with a model library of 36 compounds prepared from a combination of three Boc protected L-amino acids (valine 23, phenylalanine 24, and proline 25) and 12 aromatic amines (3,4,5-trimethoxyaniline (26), 3,5-dimethylaniline (27), 3-benyloxyaniline (28), 5-aminoindane (29), 4-tert-butylamline (30), 4-biphenylamine (31), 1-3-benyloxyani-line (28), 5-aminoindane (29), 4-tert-butylaniline (30), 4-biphenylamine (31), 1-aminonaphthalene (32), 4-tritylaniline (33), 2-aminoanthracene (34),... 

Azetidine-2-carboxylic acid, the lower homolog of proline, has been isolated from Convallaria majalis (lily of the valley) 40,44), Polygonatum officinalis (Solomon s seal) 153), and Polygonatum multiflorum 45). Fowden and Steward 47) surveyed plants from 56 genera for nitrogenous compounds and found azetidine-2 -carboxylic acid to be restricted to members of the Liliaceae. In some species it was identified in leaf, stem, and root but was more commonly found in the seed. In Polygonatum, azetidine-2-carboxylic acid accounted for 75% or more of the total nonprotein nitrogen in the rhizome 45). There was no evidence that it occurred as a constituent of protein. 

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). 

In the first step bromocriptine 2 is isomerized to 2a, followed by an attack on proline ring in aminocyclol moiety of the molecule (formation of a new double bound on lO -ll, and bromination). This dibromo-compound 5 is brominated additionally on C-2 -propyl group. Tribromo-compound fi is very lipophilic and practically devoid of pharmacological activity. Hydroxy group and amide groups remain intact after all these reactions. 

Proline is also able to detoxify free radicals by forming long-lived adducts with them (Floyd Zs-Nagy, 1984). Another group of compounds with... 

The organic solutes shown to be related to stress adaptation include sugars, polyols, tertiary N compounds, amino acids and organic acids. Of particular note are compounds such as proline, glycine betaine and reducing... 

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