L-Pyrrolidine-2-carboxylic acid

Wannamaker W, et al. (S)-l-((S)-2- (l-(4-amino-3-chloro-phe-nyl)-methanoyl)-amino -3,3-dimethyl-butanoy l)-pyrrolidine-2-carboxylic acid ((2R,3S)-2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-amide (VX—765), an orally available selective interleukin (IL)-converting enzyme/caspase-1 inhibitor, exhibits potent antiinflammatory activities by inhibiting the release of IL-lbeta and IL-18. J. Pharmacol. Exp. Ther. 2007 321 509-516. 

G.A. Choghamarani, P. Zamani, Synthesis of 2,3-dihydroquinazolin-4(lH)-ones via one-pot three-component reaction catalyzed by L-pyrrolidine-2-carboxylic acid-4-hydrogen sulfate (supported on silica gel) as novel and recoverable catalyst, J. Iran. Chem. Soc. 9 (2012) 607-613. 

The coordination of [Me2Sn(IV)f to captopril (cap) [(2S)-l-[(2S)-2-methyl-3-sulfanyl propanoyl]pyrrolidine-2-carboxylic acid] in aqueous solution was studied by means of pH-metric titration, electrospray mass spectrometry, H NMR, and Mossbauer spectroscopies in the 2-11 pH range. The results obtained proved that only monomeric complexes are formed in solution. In the acidic pH... 

Reactant A R-l(2-hydroxy-ethyl)-pyrrolidine-2-carboxylic acid adamantan-2-ylamide (Fig. 10.2)... 

Fmoc-4-terI-butyloxycarbonylaminophenylalanine, Fmoc-4-benzoylpheny-lalanine, Fmoc-D-tetrahydroisoquinoline-3-COOH, Fmoc-thiazolidine-4-carboxylic acid, Fmoc-D-propargylglycine, Fmoc-3-(2-naphthyl)alanine, Fmoc-D-3-(2-naphthyl)alanine, Fmoc-3-aminobenzoic acid, (25,45) Fmoc-4-amino-l-Boc-pyrrolidine-2-carboxylic acid, (d stands for d configuration.)... 

Anon. Pyrrolidine-2-carboxylic acid (L-proline). Synlett 2003, 582-583. 

Early work with zinc metalloprotease inhibitors focused on the well-characterized agents captopril ((2S)-l-[(2S)-2-methyl-3-sulfanyl-propanoyl] pyrrolidine-2-carboxylic acid) and phos-phoramidon (/V-alpha-i,-rhamnopyranosyloxy[hydroxyphosphinyl -i,-leucyl-L-tryptophan). These compounds, however, were found to have little inhibitory activity against BoNT (Adler et al., 1994, 1999a). The poor efficacy of captopril was suggested to stem from unfavorable steric constraints in the binding of proline at the active site of BoNT (Schmidt and Stafford, 2002). 

Extension of the enamine-mediated carbonyl a-amination strategy to the generation of quaternary stereogenic centers at the a-position of a-branched aldehydes under catalysis by prohne 1 [8, 9], pyrrolidine tetrazole 3 [10, 11], or L-azetidin-2-carboxylic acid 4 [8] has also been explored (Table 11.1). The observed enantio-selectivities ranged from essentially none to >99%. Derivatives of 2-phenylpropanal gave better enantioselectivities than a,a-dialkyl substituted aldehydes. Erase and coworkers [11] employed microwave irradiation to accelerate the rate of proline-catalyzed amination, and found that yields as well as enantioselectivity can be somewhat improved with shorter reaction times. It appears that the pyrrolidine tetrazol 3 was a more effective catalyst than L-proline 1 for the amination of 2-phenylpropanal derivatives [10,11]. Subsequent reduction of adducts and cyclization could be carried out to afford the respective a-amino alcohols or the A-amino-oxazolidinones. 

A method for the synthesis of the derivative of A-(2-nitrophenyl) pyrrolidine-2-carboxylic acid 171b involves alcoholysis of 1-(5-chloro-2-nitrophenyl)-2-trichloroacetyl-l//-pyrrole 175, which is in mm obtained as a result of a two-stage process from 5-chloro-2-nitroaniline 173 (Silvestri et al. 2000). In this case, reductive cyclization is realized successfully with iron powder in acetic acid (60 °C, 3 h) (Scheme 3.51). 

L-Pyrrolidine-2-carboxyiic acid-4- (S)-(ert-Butyl pyrroiidlne-2-carboxylate (CAT-21) hydrogen suifate on siiica gei (CAT-20)... 

C14H27NO2 l-heptyl-pyrrolidine-2-carboxylic acid ethyl ester 30103-33-4 ... 

D. 2(S)-(fl-tert-Butoxycarbonyl-a-(R)-hydroxyethyl)-4-(R)-hydroxy-pyrrolidine- 1-carboxylic acid, tert-butyl ester. The identical procedure was followed, in this case using the (,S)-BINAP catalyst (5)-l. Hydrogenation is conducted for 64 hr, and the reaction mixture is then transferred to a 250-mL, round-bottomed flask and concentrated to dryness. The residue is dissolved in 17 mL of methanol and cooled to 15°C. After the slow addition of 7 mL of DI water, the solution is aged for 15 min gradually forming a thin slurry. More DI water (75 mL) is added over 1 hr and the mixture is allowed to stand for an additional 1 hr at 15°C. The resulting crystals (Note 19) are filtered at 15°C, washed with 10 mL of 1 4-MeOH water, and then dried overnight in a vacuum oven (35°C, 686 mm) to yield 7.0 g (70%) of (R)-hydroxy ester 4b (Note 20). 

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). 

Preparation of thiophene-2-carboxylic acid (2- 3-[3-(4-chloro-phenoxy)-pyrrolidin-l-yl]-2-hydroxy-propoxy -phenyl)-amide... 

Condensation of 9-chloromethyl-3,6,7-trimethox3rphenanthrene with methyl L-prolinate yielded methyl 3,6,7-trimethoxy-i l-(9-phenanthryl-methyl)pyrrolidine-2-carboxylate (XVII). The corresponding acid obtained by hydrolysis was cyclized by polyphosphoric acid to 9,11,12,13, 13a, 14-hexahydro-3,6,7-trimethoxy-14-oxodibenzo[/, ]pyrrolo[l,2-6]-isoquinoline (XVIII). 

L-ProNne, Pro pyrrolidine-2-carboxylic add, a pro-teogenic amino add. Pro is very soluble in water, but is also soluble in ethanol, so it can be separated from other amino adds by ethanol extraction. Being an imi-no add, it forms a yellow color with ninhydrin, rather than the purple color characteristic of a-amino acids... 

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