Proline control

F Dick, M Schwaller. SPPS of peptides containing C-terminal proline racemization free anchoring of proline controlled by an easy and reliable method, in HLS Maia, ed. Peptides 1994. Proceedings of the 23rd European Peptide Symposium. Escom, Leiden, 1995, pp 240-241. 

Fig. 17. The rate and extent of incorporation of L-proline- C into protein by 5. anti-hioiicus following previous incubation in the presence of 3-methyl-DL-proline. Control 0---o 3-methylproline 0.1 jxg/ml, n—o i.o [xg/ml, - . Under these conditions actin-...

Besides high effectiveness in the diastereoselective control of nucleophilic addition reactions, another major goal in the design of chiral auxiliaries is the use of readily available, chiral starting materials. The hexahydro-l//-pyrrolo[l,2-c]imidazole derivatives 9a-e are examples which use the inexpensive amino acid L-proline (7) as starting material. 

One may conclude that the rate-determining step of the renaturation is at least partly influenced by the cis-trans isomerization of the peptide bond the secondary nitrogen atom of which arises from proline. Otherwise, only the entropy-controlled slow nuclea-tion should be observed kinetically. The covalent bridging through Lys-Lys, therefore, gives rise not only to thermodynamic stabilization of the triple helix but also to kinetic properties which have hitherto been observed in the case of type III procollagen146) and its aminoterminal fragment Col 1-3144). 

The enantioselectivity of Sn(II) enolate reactions can be controlled by chiral diamine additives. These reagents are particularly effective for silyl thioketene acetals.162 Several diamines derived from proline have been explored and l-methyl-2-(l-piperidinomethyl)pyrrolidine 21 is an example. Even higher enantioselectivity can be achieved by attachment of bicyclic amines to the pyrrolidinomethyl group.163... 

Cycloaddition of the cyclic nitrone derived from proline benzyl ester with alkenes proceeds readily to give isoxazolidines with good regio-and stereoselectivity (Eq. 8.47).68 The reaction favors exo-mode addition. However, certain cycloadditions are reversible and therefore the product distribution may reflect thermodynamic rather than kinetic control. 

Fig. 3. Lightmicroscope radioautographs ofintact tubes from pollen germinated 4 h in a medium containing [14C]-proline with or without the proline analogue, azetidine-2-carboxylic acid (AZC). A = 1.0 mM AZC, B = 0.1 mM AZC, C = 0.01 mM AZC, D = 0.001 mM AZC, E = Control. From Dashek and Mills (50), with permission. 

Enantioselective addition of R2Zn to aldehydes. Corey and Hannon2 have prepared the diamino benzylic alcohol 1 from (S)-proline and (lS,2R)-( + )-ephed-rine and report that the chelated lithium salt of 1 is an effective catalyst for enantioselective addition of diethylzinc to aromatic aldehydes. Thus benzaldehyde can be converted into (S)-( - )-3 with 95% ee, via an intermediate tridentate lithium complex such as 2 formed from 1. Similar reactions, but catalyzed by diastereomers of 1, show that the chirality of addition of dialkylzincs to aldehydes is controlled by the chirality of the benzylic alcohol center of 1. 

The chiral auxiliaries anchored to the substrate, which is subjected to diastereoselective catalysis, is another factor that can control these reactions. These chiral auxiliaries should be easily removed after reduction without damaging the hydrogenated substrate. A representative example in this sense is given by Gallezot and coworkers [268], They used (-)mentoxyacetic acid and various (S)-proline derivates as chiral auxiliaries for the reduction of o-cresol and o-toluic acid on Rh/C. A successful use of proline derivates in asymmetric catalysis has also been reported by Harada and coworkers [269,270], The nature of the solvent only has a slight influence on the d.e. [271],... 

PAGE Phe Pro PSD QC Q-ToF Q-ToF-LC-MS-MS polyacrylamide gel electrophoresis phenylalanine proline post-source decay quality control quadrupole time-of-flight mass analyser quadrupole time-of-flight mass analyser in combination with (high performance) liquid chromatography and tandem mass... 

A method for highly efficient asymmetric cyclopropanation with control of both relative and absolute stereochemistry uses vinyldiazomethanes and inexpensive a-hydroxy esters as chiral auxiliaries263. This method was also applied for stereoselective preparation of dihydroazulenes. A further improvement of this approach involves an enantioselective construction of seven-membered carbocycles (540) by incorporating an initial asymmetric cyclopropanation step into the tandem cyclopropanation-Cope rearrangement process using rhodium(II)-(5 )-N-[p-(tert-butyl)phenylsulfonyl]prolinate [RhjtS — TBSP)4] 539 as a chiral catalyst (equation 212)264. 

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