Pipecolate

Pip = D-pipecolic acid MeAsp = A -methylaspartic acid. The amphomycin family member having (+)-3-anteisotridecenoic acid is shown not shown is... 

Ornithine, proline, hydroxyproline, pipecolic acid and sarcosine yield red zones, glycine greenish-brown and the other amino acids weakly brown ones [3]. The colors of the zones are different if an alcoholic solution of potassium carbonate is used for basification instead of dipping solution II. 

Perhydro derivatives of pyrido[l,2-7)][l,2]oxazines are frequently applied in the total synthesis of various alkaloids to control the stereochemistry, and pyrido[l,2-c][l,3]oxazines and [l,3]oxazino[3,4-u]quinolines were also used in the stereoselective syntheses of different alkaloids. Perhydropyrido[l,2-c][l,3]oxazines and their benzologs are formed form 2-(2-hydroxyethyl) piperidines and from their benzologs to justify the stereochemistry of 2-(2-hydroxyethyl) derivatives. Different optically active pipecolic acids can be prepared via 4-phenylperhydropyrido[2,l-c][l,4]oxazin-l-ones. 

Treatment of perhydropyrido[2,l-c][l,4]oxazin-l-ones 236 with vinyl and 1 -chloroethyl chloroformate in the presence of 4A molecular sieves afforded ring-opened (2i )-pipecolic acid derivatives 237 (97SL799, 98EJOC2461, 98T10309). Similarly, perhydropyrido[l,2-c][l,4]oxazin-l-one 238 yielded (2S)-pipecolic acid derivative 239 (98T10309). 

Treatment of the appropriate pipecolic amide 396 with NEta afforded optically active or racemic perhydropyrido[l,2-a]pyrazine-l,4-dione (397) (97USP5703072). (9a5)-Perhydropyrido[l,2-a]pyrazin-3-one (400) was obtained by cyclization of piperidine 398, and the catalytic hydrogenation of quaternary salt 399 over Pd/C (99H(51)2065). 

Dab = D-erythro-aj3-diaminobutyric acid Dab = L-threo-or,)3-diaminobutyric acid Pip = D-pipecolic acid... 

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

Cyclization of the (E)- and (Z)-A-hexenylglycine derivatives ( )-l and (Z)-l with formic acid leads to pipecolic acid derivatives, in which formation of the new C-C bond occurs with high stereoselectivity, but subsequent formylation of the intermediary carboeation proceeds with low stereoselectivity89. 

Pipecolic acid has been isolated and identified by various researchers from several legumes, hops, mushrooms, potato tuber, green pepper, tulip, celery, asparagus, Rhodesian teak, barley, and coconut milk. Grobbelaar et al. 58) isolated large quantities of free (-)pipe-colic acid from Phaseolus vulgaris. 

Scheme 7.25 Enzymatic resolution of pipecolic methyl esters.

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

An enzyme that catalyzes the reduction of A -piperidein-2-carboxylate to piperidine-2-car-boxylate (r-pipecolate) in the catabolism of o-lysine by Pseudomonas putida ATCC12633 is an NADPH-dependent representative of a large family of reductases that are distributed among bacteria and archaea (Muramatsu et al. 2005). It also catalyzes the reduction of A -pyrrolidine-2-carboxylate to L-proline. 

A reaction related to alkene-aldehyde coupling is the alkene-imine coupling. A one-pot cyclization involving such a reaction (Eq. 3.27) proceeds smoothly in a mixture of water-THF. The reaction has been used in the asymmetric synthesis of pipecolic acid derivatives.114... 

Alder-Ene Reactions. An ene-iminium one-pot cyclization proceeds smoothly in a mixture of water-THF (Eq. 12.66). 138 The reactivity of the ene-iminium substrates is highly dependent on the substitution pattern of the ethylenic double bond. This methodology can be used to form homochiral pipecolic acid derivatives. 

The lactone structure is a versatile synthetic intermediate that can be used to access a variety of 4-substituted pipecolic derivatives. Hydrogenolysis in meth-anolic HCl, followed by hydrolysis and desalting, gave 4-hydroxypipecolic... 

Pipecolic acids substituted at the 2-position were obtained from lactones by simultaneous 0- and N-deprotection on 10% Pd/C (0.08 mol Pd/mol) in EtOH-AcOH (2 1) for 1 hour (Scheme 4.75).318... 

The benzyl C-N bond was hydrogenolyzed during a double O- and N-deprotection on Pd/C in mild acidic medium.352 The reaction flask was charged with a solution of the substrate in a mixture of EtOH-AcOH (2 1). After the addition of 10% Pd/C (0.085 mol Pd/mol compound) the apparatus was charged with hydrogen. The reaction was complete within 30 min to 1 hour under stirring and enantiomerically pure (S)-pipecolic acid (29) was produced (Scheme 4.105).353... 

Armstrong, D.W., Zukowski, J., Ercal, N., Gasper, M.P. (1993b). Stereochemistry of pipecolic acid found in the urine and plasma of subjects with peroxisomal defieciencies. J. Pharm. Biomed. Anal. 11, 881-886. 

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