L-Pipecolic acid

Black hypothesis 265, 283 bleach (NaOCl) 534 A-r-BOC-L-pipecolic acid 601,620, 622... 

CioHi S0-56-S) see Sobrerol ( )-a-pinene oxide (Ci( H,jO 95044-43-2) see Sobrerol L-pipecolic acid... 

Synthesis of L-Pipecolic Acid with A -Piperidine-2-carboxyiate Reductase from Pseudomonas putida... 

L-Pipecolic acid, a key component of many antibiotic and anticancer biomolecules, serves as an important chiral pharmaceutical intermediate. We have developed an enzyme-coupled system consisting of zl -piperidine-2-carboxylate reductase (Pip2C) from Pseudomonas putida, glucose dehydrogenase (GDH) from Bacillus subtilis, and L-lysine a-oxidase from Trichoderma viride, affording L-pipecolic acid from L-lysine in high yield with an excellent enantioselectivity (Figure 10.2). ... 

After 17 h, a titre of 210 him (27 g L ) L-pipecolic acid was achieved with satisfactorily high optical purity (>99.7 % ee). The molar yield of L-pipecolic acid relative to L-lysine was 90 %. 

L-Pipecolic acid can be isolated from the resultant reaction solution by commonly used methods, such as ion-exchange chromatography and crystallization, as described previously. ... 

Enantiomeric excess was determined by high-performance hquid chromatography with a Chiralpak WE column (4.6 mm x 250 mm, Daicel Chemical Industries, Tokyo), 2 him CUSO4, 0.75 ruL min, 50 °C, monitored at 254 nm L-pipecolic acid r = 14.7 min, D-pipecolic acid rt= 18.0 min. 

The procedure can provide a higher amount of L-pipecolic acid in a shorter reaction time than the previously reported system, indicating that it is applicable in industrial production of L-pipecolic acid. A similar system was successfully employed in the enzymatic synthesis of several cyclic amino acids by our group. ... 

Muramatsu, H., Mihara, H., Yasuda, M., Ueda, M., Kurihara, T. and Esaki, N., Enzymatic synthesis of L-pipecolic acid by d -piperidine-2-carboxylate reductase from Pseudomonas putida. Biosci. Biotechnol. Biochem., 2006, 70, 2296. 

Rashed, M.S. et al.. Determination of L-pipecolic acid in plasma using chiral liquid chromatography-electrospray tandem mass spectrometry, Clin. Chem., 47, 2124, 2001. 

The naturally occurring cis-5-hydroxy-L-pipecolic acid 40 was prepared from l-G1u in a stereospecific multistep reaction (88TL2231). Protected l-Glu was transformed into A -hydroxycycloornithine 41 in seven steps (94JOC929). 

Scheme 2.17 Synthesis of L-pipecolic acid 42 using a lysine cyclodeaminase.

Swansonine and castanospermine synthesis starts with the a-aminoacid, y-semialadehyde and, via piperidine-6-carhoxyhc acid synthetases, L-pipecolic acid. This compound is a substrate to HSCoA and acetyl-CoA. As a result of this activity, the second ring is established. Subsequently, it changes to 1 -indolizidinone and, by oxidation reaction, produces castanospermine or swansonine (Figure 50). 

The a is L-lysine, as in the case of piperidine, but the f3 is different. The /3 is a-aminoadipic acid 6-semialdehyde. The q> is L-pipecolic acid, which is synthesized in plants from piperideine-6-carboxylic acid. In the case of many other organisms, the obligatory intermedia (q>) is derived from the /3. The

ring structure. The indolizidine nucleus will be formed only in the synthesis of the x- The deep structmal change occms when

Claisen reaction with acetyl or malonyl CoA (Cra/mCoA) and the ring closme process (by amide or imine) to 1-indolizidinone, which is the x- The second obligatory intermedia ( k ) only has the indolizidine nucleus. 

Reaction of 164 with acetic anhydride, reaction of isatin with L-pipecolic acid, or reaction of pyrrolidine with isatin in acetic anhydride gives a substance known as isatin blue. Proline and isatin give the same product and the blue color is the basis of a color test for such compounds.463-468 The structure 166 has been proposed for isatin blue,461 and other related compounds have also been prepared.461... 

The authors reported the chiral separation of proline and thereonine amino acid up to 20 and 6g, respectively, in a single run. Micropreparative resolution of lecucine was presented. The resolution was discussed with respect to the degree of sorbent saturation with copper(II), elution rate, eluent concentration, temperature, and column loading condition [16]. Weinstein [74] reported the micropreparative separation of alkylated amino acids on a Chiral ProCu column. In another article, a preparative chiral resolution of 3-methylene-7-benzylidene-bicyclo[3.3.1]nonane was achieved on 7.5% silver(I)-d-camphor- 10-sulfonate CSP [75]. Later, Shieh et al. [71] used L-proline-loaded silica gel for the chiral resolution of (ft,5 )-phcnylcthanolaminc as the Schiff base of 2-hydroxy-4-methoxyacetophenone. Gris et al. [76] presented the preparative separations of amino acids on Chirosolve L-proline and Chirosolve L-pipecolic acid CSPs. 

L-Pipecolic acid is a marker for peroxisomal disorders. Three EPMEs were used for the enantioanalysis of L-pipecolic acid [42]. These electrodes are based on carbon paste impregnated with different... 

An EPME based on vancomycin was proposed for the assay of D-pipecolic acid [50]. The linear concentration range for the proposed enantioselective membrane electrode is 10 9-10 6mol/L with the slope of electrode function 60.2 mV/p(D-pipecolic acid). The enantioselectivity was determined over L-pipecolic acid. The proposed electrode could be reliably employed for the assay of D-pipecolic acid in serum samples. 

Lysine.—Lysine is a common precursor of piperidine alkaloids. Of the two enantiomers of this amino-acid, the L-isomer is the more direct precursor, in plants, for piperidine alkaloids, e.g. anabasine, whereas D-lysine is more directly implicated in the biosynthesis of pipecolic acid (24)1,2,23 (cf Vol. 7, p. 7). It has now been shown that a pathway exists in the plant Nicotiana glauca,24 and also in the micro-organism Neurospora crassa2S which transforms D-lysine into L-lysine by way of L-pipecolic acid (24). 

In accord with a general body of evidence on the biosynthesis of alkaloids as against that of pipecolic acid (see above), L-lysine has been shown to be the preferred precursor for lupanine (27) and D-lysine the preferred precursor for l-pipecolic acid (24) in Lupinus angustifolia,36 A high retention of tritium, present at C-4 and C-5 in the lysine, on formation of (27) is to be noted. 

In a similar way, D,L-pipecoUc add was converted to L-pipecolic acid [49]. However, the use of sodium borohydride, which slowly decomposes in aqueous solution, causes a significant rise in the pH value, which has to be controlled and which interferes with the necessary repeated cycles. Turner and Fotheringham expanded the applicability of the method, using milder and water stable reducing agents [50] and applying amino acid oxidases with either D- or L-spedficity. 

Gatto et al m characterized the mechanism of L-pipecolic acid formation by cyclodeaminase RapL from L-lysine within rapamycin biosynthesis, which is a hybrid NRP—polyketide antibiotic (Figure 25(a)). RapL was characterized by biochemical assays to require cofactor nicotinamide adenine dinucleotide (NAD+) and an oxidative cyclodeamination reaction mechanism corresponding to ornithine cyclodeamination was proposed based on ESI-FTMS analysis of RapL reaction products (Figure 25(b)). 

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