3105-95-1Relevant articles and documents
Preparation and reaction of titania particles encapsulated in hollow silica shells as an efficient photocatalyst for stereoselective synthesis of pipecolinic acid
Chandren, Sheela,Ohtani, Bunsho
, p. 677 - 679 (2012)
Hollow coreshell particles of titania core and silica shell were synthesized by multistep process, and the coreshell particles showed improved stereoselectivity in the photocatalytic redox-combined synthesis of L-pipecolinic acid from L-lysine in an aqueous suspension without reducing the original activity of the bare titania core.
Enzymatic synthesis of L-pipecolic acid by Δ1-piperideine- 2-carboxylate reductase from Pseudomonas putida
Muramatsu, Hisashi,Mihara, Hisaaki,Yasuda, Mari,Ueda, Makoto,Kurihara, Tatsuo,Esaki, Nobuyoshi
, p. 2296 - 2298 (2006)
L-Pipecolic acid is a chiral pharmaceutical intermediate. An enzymatic system for the synthesis of L-pipecolic acid from L-lysine by commercial L-lysine α-oxidase from Trichoderma viride and an extract of recombinant Escherichia coli cells coexpressing Δ1-piperideine-2- carboxylate reductase from Pseudomonas putida and glucose dehydrogenase from Bacillus subtilis is described. A laboratory-scale process provided 27 g/l of L-pipecolic acid in 99.7% e.e.
Biotransformation of L-lysine to L-pipecolic acid catalyzed by L-lysine 6-aminotransferase and pyrroline-5-carboxylate reductase
Fujii, Tadashi,Mukaihara, Manabu,Agematu, Hitosi,Tsunekawa, Hiroshi
, p. 622 - 627 (2002)
The enzyme involved in the reduction of Δ1-piperideine-6- carboxylate (P6C) to L-pipecolic acid (L-PA) has never been identified. We found that Escherichia coli JM109 transformed with the lat gene encoding L-lysine 6-aminotransferase (LAT) converted L-lysine (L-Lys) to L-PA. This suggested that there is a gene encoding "P6C reductase" that catalyzes the reduction of P6C to L-PA in the genome of E. coli. The complementation experiment of proC32 in E. coli RK4904 for L-PA production clearly shows that the expression of both lat and proC is essential for the biotransformation of L-Lys to L-PA. Further, We showed that both LAT and pyrroline-5-carboxylate (P5C) reductase, the product of proC, were needed to convert L-Lys to L-PA in vitro. These results demonstrate that P5C reductase catalyzes the reduction of P6C to L-PA. Biotransformation of L-Lys to L-PA using lat-expressing E. coli BL21 was done and L-PA was accumulated in the medium to reach at an amount of 3.9 g/l after 159 h of cultivation. It is noteworthy that the ee-value of the produced pipecolic acid was 100%.
Preparation method of caine drug intermediate (S)-2-piperidinecarboxylic acid
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, (2021/06/22)
The invention discloses a preparation method of a caine drug intermediate (S)-2-piperidinecarboxylic acid. The preparation method specifically comprises the following steps of a) carrying out a one-pot reaction on 5-chlorovaleraldehyde, L-phenylglycinol and trimethylsilyl cyanide under the action of a catalyst A to obtain a compound as shown in a formula (I), wherein the catalyst A is magnesium diiodide, magnesium dibromide and magnesium perchlorate, (b) carrying out catalytic hydrogenation reaction on the compound as shown in the formula (I) to obtain (S)-2-cyano piperidine as shown in a formula (II), and (c) hydrolyzing the compound as shown in the formula (II) to obtain (S)-2-piperidinecarboxylic acid as shown in a formula (III). The preparation method utilizes cheap and easily available organic raw materials, and has the advantages of simple operation, mild reaction conditions, good stereoselectivity, high yield and the like.
Preparation method of bupivacaine and intermediate (S)-2-piperidinecarboxylic acid thereof
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Paragraph 0021; 0067-0071, (2021/06/13)
The invention discloses bupivacaine and a preparation method of an intermediate (S)-2-piperidinecarboxylic acid of the bupivacaine; wherein the intermediate (S)-2-piperidinecarboxylic acid is prepared by taking (R)-4-benzyl-2-oxazolidinone as a chiral auxiliary agent through amidation, asymmetric alkylation, hydrolysis, cyclization and auxiliary group removal; wherein the prepared (S)-2-piperidinecarboxylic acid is used as a raw material to prepare the local anesthetic (S)-bupivacaine. The method utilizes cheap and easily available organic raw materials, and has the advantages of simple operation, mild reaction conditions, good stereoselectivity, high yield and the like.
A convenient and highly enantioselective synthesis of (S)-2-pipecolic acid: an efficient access to caine anesthetics
Yang, Yuyan,Li, Hua,You, Zhonglin,Zhang, Xingxian
, p. 3084 - 3089 (2021/08/12)
A novel and enantioselective synthesis of (S)-2-pipecolic acid (5) has been achieved from Oppolzer’s sultam (1) and ethyl N-(diphenylmethylene)glycinate (2) as readily available starting materials. The highly stereoselective alkylation of chiral glycine intermediate (3) with 1,4-dibromobutane afforded the key backbone of (S)-2-pipecolic acid (5) in one-step that was utilized into the preparation of the local anesthetics mepivacaine, ropivacaine and bupivacaine.
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
, 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.
Preparation method of (S)-2-piperidinecarboxylic acid
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Paragraph 0111-0120, (2020/12/09)
A preparation method of (S)-2-piperidinecarboxylic acid comprises the following steps: under the catalysis of Lewis acid, carrying out condensation reaction on L-camphor sulfonamide (I) and diphenyl imine ester (II) to generate a compound (III); enabling the compound (III) and the compound (IV) to be subjected to asymmetric alkylation under the action of strong base, imine hydrolysis under an acidic condition and intramolecular cyclization by a one-pot method to obtain a compound (V); and removing a chiral auxiliary group from the compound (V) under an alkaline condition to obtain a target compound (S)-2-piperidinecarboxylic acid (TM), wherein the formulas (I), (II), (III), (IV) and (V) are described in the specification. The target product can be obtained through three steps in total, themethod has the advantages of cheap and easily available raw materials, short route, high yield, good stereoselectivity and the like, and the (S)-2-piperidinecarboxylic acid is an important chiral intermediate of multiple medicines at present and has a good market prospect.
Furan-Derived Chiral Bicycloaziridino Lactone Synthon: Collective Syntheses of Oseltamivir Phosphate (Tamiflu), (S)-Pipecolic acid and its 3-Hydroxy Derivatives
Chavan, Subhash P.,Gonnade, Rajesh G.,Kadam, Appasaheb L.,Shinde, Shrikrishna S.
, (2020/02/05)
A unified synthetic strategy for oseltamivir phosphate (tamiflu), (S)-pipecolic acid, and its 3-hydroxy derivatives from furan derived common chiral bicycloaziridino lactone synthon is described here. Key features are the short (4-steps), enantiopure, and decagram-scale synthesis of common chiral synthon from furan and its first-ever application in the total synthesis of biologically active compounds by taking the advantages of high functionalization ability of chiral synthon.
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.
