1723-00-8Relevant articles and documents
Kinetic Resolution of Pipecolic Acid Using Partially-Purified Lipase from Aspergillus niger
Ng-Youn-Chen, M. Christine,Serreqi, Alessio N.,Huang, Qingli,Kazlauskas, Romas J.
, p. 2075 - 2081 (1994)
Synthesis of biologically active peptides, alkaloids, and immunosuppresants such as FK506 requires enantiomerically-pure pipecolic acid (2-piperidinecarboxylic acid).We report an efficient kinetic resolution of pipecolic acid esters by enzyme-catalyzed hydrolysis.We screened commercially available hydrolases and identified crude lipase from Aspergillus niger (ANL) as the most enantioselective catalyst for the hydrolysis of (+/-)-methyl pipecolate, E=20+/-4 in favor of the (S)-enantiomer at pH 7.Changing of the ester group to n-pentyl or n-octyl did not increase the enantioselectivity, while addition of an N-acetyl group decreased the enantioselectivity.Partial purification of ANL by fractional precipitation with ammonium sulfate (25-45percent saturation) increased the enantioselectivity to >100.A synthetic scale resolution of (+/-)-n-octyl pipecolate using this partially purified ANL gave (S)-(-)-pipecolic acid (93percent ee, 0.89 g) and (R)-(+)-pipecolic acid (97percent ee, 1.20 g).Further purification of ANL confirmed that the lipase (apparent molecular weight of 32 kDa), and not an impurity, was responsible for the enantioselective hydrolysis of octyl pipecolate.
Preparation, characterization and photocatalytic performance of titania particles encapsulated in hollow silica shells as an efficient photocatalyst for redox-combined stereoselective synthesis of l-pipecolinic acid from l-lysine
Chandren, Sheela,Ohtani, Bunsho
, p. 50 - 59,10 (2012)
Hollow core-shell particles of a titania core and a silica shell, the latter of which was highly porous, water-swollen and not directly connected to the former, were synthesized by a multistep process including carbon and silica coatings followed by calcination of the carbon-layer combustion. The core-shell particles suspended in aqueous solutions of l-lysine showed improved stereoselectivity in photocatalytic redox-combined synthesis of l-pipecolinic acid (l-PCA), maintaining l-lysine conversion and PCA selectivity, compared with that by bare titania particles, presumably due to the acidic microenvironment of the titania core to control the position of oxidation by positive holes as the first step of the redox-combined process. Modification of the silica layers to acidify them was also beneficial for improvement of optical purity of the product, PCA.
Photocatalytic redox-combined synthesis of L-pipecolinic acid from L-lysine by suspended titania particles: Effect of noble metal loading on the selectivity and optical purity of the product
Pal, Bonamali,Ikeda, Shigeru,Kominami, Hiroshi,Kera, Yoshiya,Ohtani, Bunsho
, p. 152 - 159 (2003)
Photocatalytic (> 300 nm) conversion of L-(S)-lysine (L-Lys), in its neutralized aqueous solution, into L-pipecolinic acid (L-PCA) under deaerated conditions at 298 K was investigated in detail using suspended TiO2 powders (Degussa P-25, Ishihara ST-01, and HyCOM TiO2) loaded with platinum (Pt), rhodium (Rh), or palladium (Pd). A common feature of the results of experiments using a wide variety of metal-loaded TiO2 photocatalysts is that the rate of PCA formation (rPCA) was greatly reduced when higher optical purity of PCA (OPPCA), i.e., enantio excess of the L-isomer of PCA, was obtained; higher rPCA was achieved by the use of Pt-loaded TiO2 powders, while these powders gave relatively low OPPCA. Selectivity of PCA yield (S PCA), i.e., amount of PCA production based on L-Lys consumption, also tended to increase with decrease in OPPCA, giving a master curve in the plots of OPPCA versus SPCA. Among the TiO2 powders used in this study, HyCOM TiO2 showed relatively high OPPCA and SPCA but not optimum S PCA and OPPCA simultaneously. In order to interpret such relations, the mechanism of stereoselective synthesis of the L-isomer of PCA (L-PCA) was investigated using isotope-labeled α-15N-L-lysine with quantitative analysis of incorporation of 15N in PCA and ammonia (NH3), a by-product. It was observed for several photocatalysts that the 15N proportion (P15) in PCA was almost equal to OPPCA, suggesting that oxidative cleavage by photogenerated positive holes of the ε-amino moiety of L-Lys gave optically pure L-PCA through retention of chirality at the α-carbon in the presumed intermediate, a cyclic Schiff base (α-CSB), which undergoes reduction by photoexcited electrons into PCA. From P15 in NH 3 and PCA, the selectivity of oxidation between α and ε-amino groups in L-Lys by photoexcited positive holes (h+) and the efficiency of reduction of α-CSB (produced via ε-amino group oxidation to give optically pure PCA) and ε-CSB (produced via α-amino group oxidation to give racemic PCA) by photoexcited electrons (e-) were calculated. The former was found to be independent of the kind of photocatalyst, especially the loaded metal, while the latter was influenced markedly only by the loaded metal. It was clarified that OP PCA and SPCA obtained for various TiO2 powders used in the present study were strongly governed by the reduction stage, i.e., the efficiency of reduction of two types of CSB. When SPCA was relatively low, photocatalysts, favoring the reduction of α-CSB rather than ε-CSB, gave higher OPPCA but lower SPCA, since some ε-CSB remained unreduced to give racemic PCA. In contrast, at higher SPCA, both CSBs were reduced nonselectively and OPPCA was found to be determined mainly by the selectivity in the oxidation stage. The relatively low yield of molecular hydrogen (H2) when higher S PCA was achieved is consistent with the mechanism in which H 2 liberation occurs instead of the reduction of CSBs by e -. Thus, the general tendency of plots between OPPCA and SPCA could be explained by the above-described redox-combined mechanism of photocatalysis.
Titanium(IV) oxide photocatalyst of ultra-high activity for selective N-cyclization of an amino acid in aqueous suspensions
Ohtani, Bunsho,Iwai, Kunihiro,Kominami, Hiroshi,Matsuura, Takeshi,Kera, Yoshiya,Nishimoto, Sei-ichi
, p. 315 - 319 (1995)
Titanium(IV) oxide (TiO2) powder was prepared by the high-temperature hydrolysis of titanium(IV) tetrabutoxide in toluene as anatase crystallites of average diameter ca. 15nm.They were platinized by impregnation from aqueous chloroplatinic acid solution followed by hydrogen reduction.The catalyst was suspended in an aqueous L-lysine (Lys) solution and photoirradiated under argon at ambient temperature to obtain L-pipecolinic acid (PCA).Among several platinized commercial TiO2 powders, the present TiO2 showed the highest photocatalytic activity for both Lys consumption and PCA production.This result is attributed to both the higher activity owing to the larger surface area with lesser defects and the higher dispersion of platinum deposits acting as an efficient reduction site for a Schiff base intermediate into PCA.
Chiral separation of the clinically important compounds fucose and pipecolic acid using ce: Determination of the most effective chiral selector
Hadjistasi, Christoforos A.,Stavrou, Ioannis J.,Stefan-Van Staden, Raluca-Ioana,Aboul-Enein, Hassan Y.,Kapnissi-Christodoulou, Constantina P.
, p. 556 - 560 (2013)
In this study, simple electrophoretic methods were developed for the chiral separation of the clinically important compounds fucose and pipecolic acid. In recent years, these analytes, and particularly their individual enantiomers, have attracted considerable attention due to their role in biological functions and disorders. The detectability and sensitivity of pipecolic acid and fucose were improved by reacting them with fluorenylmethyloxycarbonyl chloride (FMOC-Cl) and 5-amino-2-naphthalene-sulfonic acid (ANSA), respectively. The enantioseparation conditions were optimized by initially investigating the type of the chiral selector. Different chiral selectors, such as polymeric surfactants and cyclodextrins, were used and the most effective ones were determined with regard to resolution and analysis time. A 10-mM β-cyclodextrin was able to separate the enantiomers of ANSA-DL-fucose and the polymeric surfactant poly(sodium N-undecanoyl-LL-leucine-valinate) was able to separate the enantiomers of FMOC-DL-pipecolic acid, with resolution values of 3.45 and 2.78, respectively. Additional parameters, such as the concentration and the pH of the background electrolyte (BGE), the concentration of the chiral selector, and the addition of modifiers were examined in order to optimize the separations. The addition of the chiral ionic liquid D-alanine tert-butyl ester lactate into the BGE was also investigated, for the first time, in order to improve resolution of the enantiomers. 2013 Wiley Periodicals, Inc.
Convenient Resolution of (+/-)-Piperidine-2-carboxylic Acid ((+/-)-Pipecolic Acid) by Separation of Palladium(II) Diastereomers Containing Orthometallated (S)-(-)-1-naphthalene
Hockless, David C. R.,Mayadunne, Renuka C.,Wild, S. Bruce
, p. 3031 - 3038 (1995)
(+/-)-Piperidine-2-carboxylic acid ((+/-)-pipecolic acid) has been resolved by the fractional crystallisation of diastereomeric palladium(II) complexes containing orthometallated (S)-(-)-1-naphthalene.The enantiomers of the acid were liberated from the individual configurationally homogeneous diastereomers of the complex in high yield with D +/- 26.0 (c 1.00, H2O).The crystal and molecular structures of both diastereomers of the complex have been determined.
Cell-free biocatalytic syntheses of l-pipecolic acid: A dual strategy approach and process intensification in flow
Benítez-Mateos, Ana I.,Calvey, Liam,Paradisi, Francesca,Roura Padrosa, David
supporting information, p. 5310 - 5316 (2020/09/17)
As an alternative to the traditional chemical synthesis or in vivo production of l-pipecolic acid, we have developed two ex vivo strategies using purified and immobilised enzymes for the production of this key building block. Firstly, a transaminase capable of lysine ?-deamination was coupled with a novel pyrroline-5-carboxylate reductase, yielding 60% conversion at the 50 mM scale with free enzymes and in situ recycling of the cofactor. A second, simpler, redox neutral system was then constructed by combining the pyrroline-5-carboxylate reductase with a lysine-6-dehydrogenase. This bienzymatic system, with catalytic amount of free cofactor yielded >99% of pipecolic acid in batch and, following co-immobilisation of both enzymes, it was applied as a packed-bed reactor in continuous flow achieving again a molar conversion of >99% with 30 min residence time, and a space-time yield up to 2.5 g L-1 h-1. The sustainability of the system was further improved by a catch-and-release strategy to purify the product, and recovery and recycling of the cofactor.
Polymer-supported (-)-8-phenylmenthyl auxiliary as an effective solidphase chiral inductor in the addition of nucleophiles to N-acyliminium Ions
Forero-Doria, Oscar,Santos, Leonardo S.,Nachtigall, Fabiane M.,Shankaraiah, Nagula
, p. 696 - 702 (2018/02/27)
Aim and Objective: According to our interest in developing new methods for the construction of intricate molecules, a reliable polymer-supported (-)-8-phenylmenthyl chiral auxiliary for the addition of different nucleophiles to chiral-supported N-acyliminium precursors were developed. Material- and Method-: Merrifield resin was employed to anchor (-)-8-phenylmenthol, which was prepared by nitration of (-)-8-phenylmenthyl chloroacetate followed by reduction of nitro group and subsequent Merrifield resin coupling. Treatment of a suspension of polymer-supported chloroformate and piperidinone in the presence of Et3N resulted in attachment of the substrate onto the solid-support. Treatment of the resulting resin with LiEt3BH/MeOH afforded methoxypiperidine in 87% yield. Then, the addition of allyltrimethylsilane, TMSCN, 2-(trimethylsiloxy)propene and triisopropylsilyloxyfuran and others to the N-acyliminium ion derived from chiral 2-methoxypiperidine carbamate was studied. Results: The stereochemical outcome of the addition of nucleophiles to the supported N-acyliminium ion derived from 2-methoxypiperidine carbamate was proposed through the Si-face, affording after resin cleavage 2-substituted piperidines in 70%-84% yields and selectivities ranging from 4:1-11.1. Moreover, the key intermediates of chiral piperidines have been employed for the synthesis of simple chiral alkaloids such as (R)-pipecolic acid, (R)-pelletierine, (S)-coniine and (R,R)-myrtine. Conclusion: The proposed supported-chiral auxiliary for asymmetric approach may be expected to result not only in efficient solid-phase syntheses of a wide range of alkaloids but also in the development of useful new solid-phase methodologies, particularly for the asymmetric additions to iminium precursors. This work describes the first example of solid-phase synthesis by using supported (-)-8-phenylmenthyl as an effective chiral inductor and would be useful for the synthesis of chiral building block libraries.
Enantioselective syntheses of (R)-pipecolic acid, (2R,3R)-3-hydroxypipecolic acid, β-(+)-conhydrine and (-)-swainsonine using an aziridine derived common chiral synthon
Chavan, Subhash P.,Khairnar, Lalit B.,Pawar, Kailash P.,Chavan, Prakash N.,Kawale, Sanket A.
, p. 50580 - 50590 (2015/06/25)
Concise total syntheses of (R)-pipecolic acid, (R)-ethyl-6-oxopipecolate, (2R,3R)-3-hydroxypipecolic acid and formal syntheses of β-(+)-conhydrine, (-)-lentiginosine, (-)-swainsonine and 1,2-di-epi-swainsonine have been accomplished starting from a common chiral synthon. The present strategy employs regioselective aziridine ring opening, Wittig olefination and RCM as the key chemical transformations.
A short enantioselective total synthesis of (R)- and (S)-pipecolic acid
Chavan, Subhash P.,Khairnar, Lalit B.,Chavan, Prakash N.,Kalbhor, Dinesh B.
, p. 1246 - 1251 (2015/02/19)
A convenient and practical total synthesis of (R)- and (S)-pipecolic acid has been achieved by utilizing chiral cis-aziridine-2-carboxylate as the common synthetic precursor. The synthesis involves regioselective reductive cleavage of the aziridine ring and Wittig olefination as key reactions.
