Substituted prolines

Mono-, di-, and trisubstituted olefins undergo osmium-catalyzed enantioselective dihydroxylation in the presence of the (R)-proline-substituted hydroquinidine 3.9 to give diols in 67-95% yields and in 78-99% ee.75 Using potassium osmate(VI) as the catalyst and potassium carbonate as the base in a tm-butanol/water mixture as the solvent, olefins are dihydroxylated stereo- and enantioselectively in the presence of 3.9 and potassium ferricyanide with sodium chlorite as the stoichiometric oxidant the yields and enantiomeric excesses of the... 

N-N cleavage of the 4-proline-substituted 4,5-dihydro-l,2,4-oxadiazoles 188, shown in Equation (31), with formic acid gave the corresponding 4,5-dihydro-l,2,4-oxadiazoles 189 in good yield and with ee up to 91% <1999H(50)995>. 

Von der Osten, C. Hedegaard, L 0stergaard, P, Lauridsen, C, Kierstein, L Branner, S. (1993) Stabilization of the detergent protease Savinase by proline substitution in Stability and Stabilization of Enzymes , Van den Tweel, W.J.J., Harder, A Buitelaar, R.M. (eds), Elsevier Science B.V., The Netherlands. 

The regioselectivity (N- vs. C-3) of the intramolecular cyclization of 2-(proline-substituted)pyrroles has been examined <05TL249>. The regiochemical outcome was dependent on electronic factors and pH. This chemistry was utilized in the preparation of the rings embodied in pyrrole-2-carboxamide marine natural products such as dibromophakeUin. 

K. Watanabe, T. Masuda, H. Ohashi, H. Mi-hara, Y. Suzuki, Multiple proline substitutions cumulatively thermostabilize Bacillus cereus ATCC7064 oligo-l,6-glucosidase. Irrefragable proof supporting the proline rule, Eur.J. Biochem. 1994, 226(2), 277-283. 

K. Watanabe, Y. Hata, H. Kizaki, Y Katsube, Y. Suzuki, The refined crystal structure of Bacillus cereus oligo-l,6-glucosidase at 2.0 A resolution structural characterization of proline-substitution sites for protein thermostabilization, J. Mol. Biol. 1997, 269(1), 142-153. 

Table 12-1 Reductive Fe release from recombinant ferritins reconstituted to constant mineral size (480 Fe/molecule) the effect of proline substitution for the highly conserved leucine 134.

Table 27.1 Direct aldol reaction of cyclohexanone and aromatic aldehydes in the presence of proline-substituted organo-catalysts(Clx-Pr-l-4, Ph-Pr-1 and -2)... 

Scheme 11. The protonation steps for the proline-substituted macrocycle 4.

About 75% of hemoglobin is in the form of an a-helix and 25% is a random coil form. Certain amino acid substitutions could shift the equilibrium between the a-helix and the random coil, thereby altering tertiary structure (Chou and Fasman, 1974). One such substitution is proline, which cannot participate in an a-helix (except as one of the first three residues). Hemoglobins Duarte and Madrid have a proline substitution for alanine, while eight other hemoglobins substitute proline for leucine. 

The effect of several amino acid replacements on toxin binding to eel electroplax membranes (Becker et al., 1992) differs from the corresponding effects on rat muscle sodium channels. Thus, proline substitution for Hyp did not affect activity in eel electroplax, and double replacement of Hyp and Hyp by Pro even increased activity by -27%. Asn replacements of Asp and Asp also slightly increased activity. These same substitutions decreased activities in rat muscle sodium channels, suggesting important structural differences between the active site on sodium channels in rat skeletal membrane and in the eel electroplax. 

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