Prolinamides

CN 6-[O-(l,l-dimethylethyl)-D-serine]-9-(N-ethyl L-prolinamide)-10-deglycinamideIuteinizing hormone-releasing factor (pig)... 

Encapsulated rhodium complexes were prepared from Rh-exchanged NaY zeolite by complexation with (S)-prolinamide or M-tert-butyl-(S)-prolinamide [73,74]. Although these catalysts showed higher specific activity than their homogeneous counterparts in non-enantioselective hydrogenations, the hydrogenation of prochiral substrates, such as methyl (Z)-acetamidocinnamate [73] or ( )-2-methyl-2-pentenoic acid [74], led to low... 

Besides sesquiterpene lactones, an alkaloid analyzed as CgH14N203 (45), was isolated from the leaves of Arnica montana L. (80). Distinction between the two possible structures 45 (amide-urethane) and 46 (ester + urea) was accomplished by a selective synthesis from prolinamide. 

It is important to mention again at this point that a general feature of the solid-state ionic chiral auxiliary approach to asymmetric synthesis is that not all chiral auxiliaries lead to high enantiomeric excesses. A case in point is found in the work of Natarajan et al. on the a-oxoamide-containing salts 43 (Scheme 10) [29]. Like the nonionic a-oxoamides discussed previously (Sect. 2.2), these compounds undergo photocyclization to p-lactam derivatives, and while the prolinamide salt behaves perfectly, leading to p-lactam 44 in 99% ee at 99% conversion, the corresponding 1-phenylethylamine salt affords nearly racemic photoproduct (3% ee at 99% conversion). The reason for this difference is... 

Fig. 3 Prolinamide (a) and 1-phenylethylamine (b) a-oxoamide salts. In the former, the anions are homochiral, while in the latter the anions have a near-mirror-image relationship...

L-proline and L-prolinamide, respectively. In both cases, the remaining (/ ru,5)-8 is free to catalyze the asymmetric Diels-Alder reaction. 

Leuprolide Leuprolide, 5-oxo-L-prolyl-L-histadyl-L-tryptophyl-L-seryl-L-tyrosyl-D-leu-cil-L-leucil-L-arginyl-iV-ethyl-L-prolinamide (30.5.9), is made synthetically [136-139]. 

Hypothalamic thyrotropic hormone releasing factor (TRF) pyroglutamyl-histidyl-prolinamide... 

A-(4-Methoxysuccinyl)-L-valyl-/V-(I-benzyl-3,3,3-trifluoro-2-hydroxypropyl)-L-prolinamide (23, R =Bzl R2=MeOSu-Val-Pro) [201... 

The AgOTf-catalyzed, PhSeBr-induced ring closure of the prolinamide-derived cinnamoylamide 92 proceeded via A-addition to the olefin, which afforded the fra r-substituted pyrrolo[l,2- ][l,4]diazepin-l,5(277)-dione 93 in 73%... 

Several prolinamides have been examined (38) catalyses the reactions of acetone with both aliphatic and aromatic aldehydes with ees up to 97%.104 It is proposed that amide and alcohol groups simultaneously donate hydrogen bonds to the aldehyde, while the gem-diphenyl moiety s bulk orients the aldehyde s approach. 

A range of prolinamides, some bearing one or more additional amino groups, have been developed as catalysts in water 107 o-hydroxyaromatic substituents likewise give high selectivity in this solvent (and in neat ketone solution) for direct aldols of aralde-hydes with ketones.108... 

BINAM - the diamino analogue of BEMOL - has been converted to its C2-symmetric bis(prolinamide).116 The latter acts as a recoverable catalyst of direct aldols in DMF-H2O at 0 °C, giving high des and ees. Butan-2-one showed significant regioselectivity, giving predominantly the iso product. 

In direct nitroso aldol reactions of a-branched aldehydes, an L-prolinamide (50) catalyses to give a-hydroxyamino carbonyl compounds which are otherwise dis- favoured ees up to 64% were found.149 Another prolinamide derivative gives similar results in a nitrosobenzene reaction.150 For proline-catalysed cases involving highly substituted cyclohexanones, DFT calculations have highlighted the roles of electro- static and dipole-dipole interactions in the level of de achieved.151 (g)... 

L-Prolinamides (71) with a pendant alcohol act as recoverable bifunctional catalysts of direct nitro-Michael addition of ketones to -nitrostyrenes, giving syn-de s up to 94% and ees up to 80%.204 The pyrrolidine provides enamine catalysis, and the side-chain donors can hydrogen-bond the nitro oxygens. 

NBD-amino acids (serine, threonine, valanie, phenylalanine, and histidine) were separated by using a 20 mM ammonium acetate buffer (pH 9.0) containing 10 mM copper acetate, 20 mM L-prolinamide, and 1 mM SDS. The elution order was the L-enantiomer followed by the D-form except in NBD-histidine. Weng et al. [32] described chiral separation of tryptophan on a poly(methyl methacrylate) microfluidic chip coated with bovine serum albumin (32 mm... 

Several reports deal with aqueous media. Acid-base catalysis by pure water has been explored, using DFT, for the model aldol reaction of acetone and acetaldehyde.125 A Hammett correlation of nornicotine analogues (28) - a series of meta- and para-substituted 2-arylpyrrolidines - as catalysts of an aqueous aldol reaction shows p = 1.14.126 Also, direct aldol reactions have been carried out in water enantioselectively, using protonated chiral prolinamide organocatalysts.127... 

Chemical Name L-Prolinamide, N-((4-oxo-2-azetidinyl)carbonyl)-L-histidyl-,... 

In 13 ml of DMF was dissolved 826.0 mg of L-histidyl-L-prolinamide 2-hydrobromide and then 2 ml of a DMF solution of 405.0 mg of triethylamine was added to the solution under ice-cooling. After maintaining 30 min under ice-cooling, the precipitates thus formed were filtered off to provide L-histidyl-L-prolinamide. 

Inverse (cis) diastereoselectivity was obtained in the intramolecular Michael addition with the cysteine-derived prolinamide analog, 63 (Scheme 2.55) [45]. 

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