Pipecolic acid structure

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... 

In addition to the 20 amino acids most frequently found in proteins a large group of amino acids occur in plants, bacteria, and animals that are not found in proteins. Some are found in peptide linkages in compounds that are important as cell wall or capsular structures in bacteria or as antibiotic substances produced by bacteria and fungi. Others are found as free amino acids in seeds and other plant structures. Some amino acids are never found in proteins. These nonprotein amino acids, numbering in the hundreds, include precursors of normal amino acids, such as homoserine and diaminopimelate intermediates in catabolic pathways, such as pipecolic acid d enantiomers of normal amino acids and amino acid analogs, such as azetidine-2-carboxylic acid and canavanine, that might be formed by unique pathways or by modification of normal amino acid biosynthetic pathways. 

Further applications for the preparation of jfi-turn mimetics have also been reported by Martens et al. with the synthesis of pipecolic acid derivatives 88 (presumably proceeding via a cyclic Schiff base - not a true post-condensation modification ) [74] and Golebiowski and co-workers who have reported the solid-supported synthesis of bicyclic diketopiperazines with the generic structure 89, via the multi-step synthesis shown in Scheme 11.18 [75]. 

The partial steps of the conjugate addition in aminocatalytic reactions are in dynamic equilibrium, and thus products are formed under thermodynamic control. This fact is translated also in the geometry of the enamine intermediates, leading to the product, which can be either E or Z (Fig. 2.9). The geometry of the enamine depends on the catalyst structure and also on the substrate. Whilst proline-catalyzed reactions form preferentially, with a-alkyl substituted ketones, the. E-isomer, enamines derived from pipecolic acid afford an approximate 1 1 mixture of the E and Z isomers [6], In turn, small- and medium-sized cyclic ketones afford the E isomer. 

Synthesis and Application of Proline and Pipecolic Acid Derivatives Tools for Stabilization of Peptide Secondary Structures... 

Isoquinuclidines 28 (aza-bicyclo [2.2.2]octanes) consist of IV-bicyclic structures which are the structural element of numerous natural occurring alkaloids with interesting biological properties (Sundberg and Smith 2002). Furthermore, these products can be readily converted to the biologically active pipecolic acids (Krow et al. 1982, 1999 Holmes et al. 1985). A retrosynthetic analysis shows that these isoquinuclidines 28 can be prepared from imines 29 and cyclohexenone 30 (Babu and Perumal 1998 Shi and Xu 2001 Sunden et al. 2005). 

Although some product from ( )-12a was formed by NlT-106, pipecolic acid 12c could not be synthesized in a preparatively satisfying way, in particular because the amide formation is twice as high as the acid formation. A structural comparison of heterocycUc amino nitriles ( )-10a-( )-12a with carbocydic P-amino nitriles... 

An enzyme has been isolated from the FK520 producer which is believed to be the key one responsible for inserting pipecolic acid into the macrocycle [114]. It is reported to be dimeric and activates pipecohc acid and several structural analogues in an ATP-dependent reaction to give an enzyme-bound amino-acyl adenylate. There is evidence that this then reacts to form a thioester linkage to the enzyme. This mechanism of activation is the same as that found in the non-ribosomal biosynthesis of peptide natural products such as gramicidin [112]. 

Fig. 7. Structure of one member of the amphomycin family where Dabe = D-erythro-a, /3-diaminobutyric acid Dab1 = l-threo-oc, /3-diaminobutvric acid Pip = D-pipecolic acid MeAsp = AT-methylaspartic acid. The amphomycin family member having (+)-3-anteisotridecenoic acid is shown not shown is...

Arguments used in interrelating these three key alkaloids will be presented in this section. The isolation of l-( — )-pipecolic acid by degradation of virosecurinine established that the alkaloid must be represented by either structure 108 or 121 (Scheme 18). Furthermore, it was shown that virosecurinine upon treatment with zinc and sulfuric... 

Rapamycin (sirolimus 2), isolated from Streptomyces hygroscopicus, is a highly functionalized 31-membered macrolide that exhibits potent antibiotic, cytotoxic, and immunosuppressive activity. FK506 (1) and rapamycin (2) are the structurally related macrolides (Fig. 1) thus, rapamycin possesses an a,p-diketoamide hemi-ketal system, a pipecolic acid moiety, 1,2,4-trisubstituted cyclohexane, and trisub-stituted tetrahydropyran rings, which are similar to those of FK506. In addition to these units, rapamycin (2) includes an ( , , )-triene moiety, two stereochemically complex aldol units, and 15 chiral centers beyond those found in FK506. 

Slaframine.—Further details are now available on the biosynthesis of slaframine (39), a toxin produced by the mould Rhizoctonia leguminicola. Both dl-[1- C]-and DL-[6- " C]-lysine afforded labelled slaframine, indicating intact incorporation of all the carbons of the amino-acid. Addition of inactive pipecolic acid (34) to the cultures diluted the lysine label in the derived slaframine, and pipecolic acid was labelled by radioactive lysine. Further carboxyl- and ring-labelled pipecolic acids [as (34)] were both well incorporated into slaframine. A clear indication is thus obtained of the biosynthetic sequence lysine —> pipecolic acid (34) — slaframine (39) 2-hydroxymethylpiperidine is not a precursor. Attention is drawn to the discovery of a similar pathway to a metabolite of similar structure also produced by R. leguminicola. ... 

C5 H,9N0,3, Mr914.19, cryst., mp. 183-185°C, [aJu -58.2° (CH3OH), a 31-membered peptide lactone in which a long-chain carboxylic acid is cyclized with l- pipecolic acid as a bridge and produced by Strepto-myces hygroscopicus. R. has antifungal, antineoplastic, and immunosuppressive activities, it is structurally related to FK-506 and exhibits a similar mechanism of action in the development of the immune response. R. was first marketed in 1999 in combination with cyclosporin and tacrolimus for use in transplantation medicine. The first total synthesis of R. was realized in 1993. 

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