176019-04-8Relevant articles and documents
A facile synthesis of 3-substituted pipecolic acids, chimeric amino acids
Makara, Gergely M.,Marshall, Garland R.
, p. 5069 - 5072 (1997)
Three protected 3-substituted pipecolic acid analogs were prepared as constrained chimeric amino acid building blocks. The concise synthetic route enables the synthesis of other derivatives with sidechain functionality of amino acids as well.
Synthesis of both enantiomers of trans 3-hydroxypipecolic acid
Greck, Christine,Ferreira, Franck,Genet, Jean Pierre
, p. 2031 - 2034 (1996)
The first syntheses of enantiomerically pure (2R, 3R) and (2S, 3S) 3-hydroxypipecolic acids 1 and 2 respectively, have been achieved from methyl 7-methyl-3-oxo-6-octenoate. Key steps involved asymmetric hydrogenation and electrophilic amination.
Insights into an unusual nonribosomal peptide synthetase biosynthesis: Identification and characterization of the GE81112 biosynthetic gene cluster
Binz, Tina M.,Maffioli, Sonia I.,Sosio, Margherita,Donadio, Stefano,Mueller, Rolf
, p. 32710 - 32719 (2010)
The GE81112 tetrapeptides (1-3) represent a structurally unique class of antibiotics, acting as specific inhibitors of prokaryotic protein synthesis. Here we report the cloning and sequencing of the GE81112 biosynthetic gene cluster from Streptomyces sp. L-49973 and the development of a genetic manipulation system for Streptomyces sp. L-49973. The biosynthetic gene cluster for the tetrapeptide antibiotic GE81112 (getA-N) was identified within a 61.7-kb region comprising 29 open reading frames (open reading frames), 14 of which were assigned to the biosynthetic gene cluster. Sequence analysis revealed the GE81112 cluster to consist of six nonribosomal peptide synthetase (NRPS) genes encoding incomplete di-domain NRPS modules and a single free standing NRPS domain as well as genes encoding other biosynthetic and modifying proteins. The involvement of the cloned gene cluster in GE81112 biosynthesis was confirmed by inactivating the NRPS gene getE resulting in a GE81112 production abolished mutant. In addition, we characterized the NRPS A-domains from the pathway by expression in Escherichia coli and in vitro enzymatic assays. The previously unknown stereochemistry of most chiral centers in GE81112 was established from a combined chemical and biosynthetic approach. Taken together, these findings have allowed us to propose a rational model for GE81112 biosynthesis. The results further open the door to developing new derivatives of these promising antibiotic compounds by genetic engineering.
A short synthesis of (2S,3S)-3-hydroxypipecolic acid
Chavan, Subhash P.,Harale, Kishor R.,Pawar, Kailash P.
, p. 4851 - 4853 (2013)
A convenient synthesis of (2S,3S)-3-hydroxypipecolic acid starting from cheap and abundant l-(+)-tartaric acid has been achieved. The strategy employs selective ester reduction and reductive lactamization as key steps.
Modular Chemoenzymatic Synthesis of GE81112 B1 and Related Analogues Enables Elucidation of Its Key Pharmacophores
Zwick, Christian R.,Sosa, Max B.,Renata, Hans
supporting information, p. 1673 - 1679 (2021/01/25)
The GE81112 complex has garnered much interest due to its broad antimicrobial properties and unique ability to inhibit bacterial translation initiation. Herein we report the use of a chemoenzymatic strategy to complete the first total synthesis of GE81112 B1. By pairing iron and α-ketoglutarate dependent hydroxylases found in GE81112 biosynthesis with traditional synthetic methodology, we were able to access the natural product in 11 steps (longest linear sequence). Following this strategy, 10 GE81112 B1 analogues were synthesized, allowing for identification of its key pharmacophores. A key feature of our medicinal chemistry effort is the incorporation of additional biocatalytic hydroxylations in modular analogue synthesis to rapidly enable exploration of relevant chemical space.
Studies on the selectivity of proline hydroxylases reveal new substrates including bicycles
Smart, Tristan J.,Hamed, Refaat B.,Claridge, Timothy D.W.,Schofield, Christopher J.
supporting information, (2019/11/26)
Studies on the substrate selectivity of recombinant ferrous-iron- and 2-oxoglutarate-dependent proline hydroxylases (PHs) reveal that they can catalyse the production of dihydroxylated 5-, 6-, and 7-membered ring products, and can accept bicyclic substrates. Ring-substituted substrate analogues (such hydroxylated and fluorinated prolines) are accepted in some cases. The results highlight the considerable, as yet largely untapped, potential for amino acid hydroxylases and other 2OG oxygenases in biocatalysis.
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.
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.
Organocatalyzed synthesis of (-)-4-epi-fagomine and the corresponding pipecolic acids
Marjanovic, Jasna,Ferjancic, Zorana,Saicic, Radomir N.
, p. 6784 - 6789 (2015/08/24)
The enantioselective synthesis of 4-epi-fagomine was accomplished starting from dioxanone and Cbz-protected benyzlamine, in 4 steps, with 18% overall yield. The key feature of this synthetic approach is the tactical combination of reactions: organocatalyz
METHOD FOR PRODUCING cis-5-HYDROXY-2-PIPERIDINECARBOXYLIC ACID DERIVATIVE, AND METHOD FOR PURIFYING cis-5-HYDROXY-2-PIPERIDINECARBOXYLIC ACID
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Paragraph 0164; 0165, (2015/07/15)
The present invention aims to provide a method for purifying cis-5-hydroxy-2-piperidinecarboxylic acid with high purity, and a method for producing its derivative. The present invention provides a method for producing a cis-5-hydroxy-2-piperidinecarboxylic acid derivative, which method comprises a step of converting cis-5-hydroxy-2-piperidinecarboxylic acid into a compound(s) of Formula (1) and/or Formula (2) (wherein R1 represents a protective group for an amino group, and R2 represents a C1-C6 alkyl group), and a method for purifying cis-5-hydroxy-2-piperidinecarboxylic acid.
