Pyrrolidine 25,3/?,1 ’5 -2- 2’-carboxy

As the key step in the synthesis of functionalized alkaloids (e.g., naphthyridinomycin), the stereo- and regioselective addition to the olefinic bond of 2-(l-alkenyl)-l-pyrrolidine carboxy-lates 10, with formation of bicyclic compounds, has been reported (Table 2)5. 

Treatment of the pyrrolidine derivative 130 with sodium hydride followed by A-methyl piperazine afforded pyrrolidino[l,2-a]quinolinone 4-carboxy-late 131 (93JPR397) (Scheme 25). 

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). 

More recently, Kaiser and coworkers reported enantiomeric specificity in the reaction of cyclohexaamylose with 3-carboxy-2,2,5,5-tetramethyl-pyrrolidin-l-oxy m-nitrophenyl ester (1), a spin label useful for identifying enzyme-substrate interactions (Flohr et al., 1971). In this case, the catalytic mechanism is identical to the scheme derived for the reactions of the cycloamyloses with phenyl acetates. In fact, the covalent intermediate, an acyl-cyclohexaamylose, was isolated. Maximal rate constants for appearance of m-nitrophenol at pH 8.62 (fc2), rate constants for hydrolysis of the covalent intermediate (fc3), and substrate binding constants (Kd) for the two enantiomers are presented in Table VIII. Significantly, specificity appears in the rates of acylation (fc2) rather than in either the strength of binding or the rate of deacylation. 

Later on, other hydroxylamine derivatives such as 1-hydroxy-2,2,6,6-tetramethyl-4-oxo-piperidine (TEMPONEH) and l-hydroxy-3-carboxy-pyrrolidine (CP-3) have been used for superoxide detection [26]. It was found that these spin traps react with both superoxide and peroxynitrite and that they might be applied for quantification of these reactive species [27]. The CP-3 radical is less predisposed to reduction by ascorbic acid and therefore is probably more suitable for superoxide detection in biological systems. 

Cefpirome Cefpirome, 6R-[6a,l (7)] -l-[(7- [(2-amino-4-thiazolyl)-(methoximino) acetyl]amino -2-carboxy-8-oxo-5-thia-l-azabicyclo[4.2.0]oct-2-en-3-yl)methyl-l-methyl]pyrrolidine chloride (32.1.2.100), is also synthesized by methods described for synthesizing third-generation cephalosporins, in particular, ceftazidime (32.1.2.82) [177,178]. 

Pathway A employed a reductive cyclization [21] to form 3-carboxy-4-alkyl-pyrrolidin-2-one (17), which could then be converted to pregabalin under acidic conditions pathway B employed a hydro lysis/reduction/decarboxylation analogous to the one used in the first-generahon route via intermediate 18 [7], and pathway C involving a heat-mediated decarboxylation to intermediate 19 followed by a hydrolysis/reduchon sequence to yield pregabalin. In pathway A, the hydro-genahon of 13 was performed in predominantly aqueous medium at neutral pH, with catalyhc amounts of Raney nickel, and afforded 17 in >95% isolated yield. The reduction could be performed at relatively high substrate loads (0.5-1.OM),... 

In 2002, 3,5-fra s-(+)-(3/ ,5/ )-3-carbomethoxycarbapenam has been reported to be prepared via a known cyclization reaction [185] starting from enantiopure carboxy pyrrolidine with di(2-pyridyl)disulfide, triphenylphosphine, and triethyl-amine in refluxing acetonitrile for 8 h (Scheme 84), [186]. 

To a solution of previously dried l-[[2-carboxy-3-(2-dimethylaminoethyl)-5-indolyl]methanesulphonyl]-pyrrolidine (1.6 g 0.0442 moles) in anhydrous quinoline (75 ml) and under atmosphere of nitrogen, cuprous oxide (160 mg 0.0011 moles) was added. The reaction mixture was heated to 190°C for 15 minutes, stirred to room temperature, poured into a mixture of 1 N hydrochloric acid (150 ml) and ethyl acetate (50 ml), shaken and decanted. The aqueous solution was washed several times with ethyl acetate, then solid sodium bicarbonate was added until pH = 7.8, and washed with n-hexane to eliminate the quinoline. The aqueous solution was made alkaline with solid potassium carbonate and extracted with ethyl acetate. The organic solution was dried (Na2S04), the solvent removed under reduced pressure when a dark oil was obtained (1.3 g yield 92%). This product was purified by column chromatography with silica gel and methylene chloride ethanol ammonium hydroxide (60 8 1) as eluent and a white foam (0.8 g) of l-[[3-(2-dimethylaminoethyl)-5-indolyl]methanesulphonyl]-pyrrolidine was obtained. To a solution of the above product (0.8 g) in acetone (30 ml), a few drops of hydrogen chloride saturated dioxan solution, were added. The precipitated solid was collected by filtration, washed with acetone and dried to give l-[(3-(2-(dimethylamino)ethyl)-5-indolyl)methanesulphonyl]-pyrrolidine hydrochloride (0.75 g). Melting point 218°-220°C. 

Hydrazoic acid attacks the carbonyl and carboxy groups of fluorenone-l-carboxylic acid simultaneously giving mainly 4-amino-phenanthridone together with some acidic material, presumably phenanthridone-4-carboxylic acid.89 The latter is best prepared by prior protection of the carboxy group with pyrrolidine.106 112 The increase in strain associated with the conversion of 4,5-dimethyl-fluorenone into 1,10-dimethylphenanthridone is reflected in the relatively low yield (50%) obtained under Schmidt conditions.22... 

Kainic acid (= 2-Carboxy-3-carboxymethyl-4-isoprenylpyrrolidine) (pyrrolidine)... 

Pyrrolidin 2-Carboxy-l -(2-nitro-phenylthio)- (Dicyclohexylamin-Salz) XV/1, 204, 218... 

H jC - CO - CH2 - COOR) Pyrrolidin 5-Carboxy-l-(4-methyl-benzolsulfonyl)-2-oxo- XV/2, 347 Thioessigsaure (Benzyjoxycarbonyl-amino)- -S-carboxymethylester XV/2, 387... 

Pyrrolidin l-Benzylsulfonyl-2-carboxy- XV/1, 242 Sulfon (l-Nitro-cyclohexyl)-phenyl-E19a, 409 (H S02R)... 

The alkaloid nicotine is present in tobacco, Nicotiana tabacum. In discussing the derivatives of pyridine it was stated (p. 858) that the e/a-mono-carboxy acid of pyridine is known as nicotinic acid and that it is obtained by the oxidation of the alkaloid nicotine. Therefore the alkaloid undoubtedly contains the pyridine group. It has been synthesized by Pictet and its constitution established as a pyridine derivative of methyl pyrrolidine. This constitution was first suggested by... 

A new NA inhibitor, 16, of influenza sialidase has been recently designed [51], see fig 17, whose molecule consists in the combination of an aromatic moiety with a y-lactame. Its structure is that of a l-(4-carboxy-2-(3-pentylamino)phenyl)-5,5-bis-(hydroxymethyl)pyrrolidin-2-one. 

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