scholarly journals Synthesis and Characterization of Novel Methyl (3)5-(N-Boc-piperidinyl)-1H-pyrazole-4-carboxylates

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3808
Author(s):  
Gita Matulevičiūtė ◽  
Eglė Arbačiauskienė ◽  
Neringa Kleizienė ◽  
Vilija Kederienė ◽  
Greta Ragaitė ◽  
...  
Keyword(s):  
Building Blocks ◽  
Dimethyl Acetal ◽  
Alkyl Halides ◽  
15N Nmr ◽  
The Novel ◽  
Subsequent Reaction ◽  
Keto Esters ◽  
15N Nmr Spectroscopy ◽  
Substituted Hydrazines

Series of methyl 3- and 5-(N-Boc-piperidinyl)-1H-pyrazole-4-carboxylates were developed and regioselectively synthesized as novel heterocyclic amino acids in their N-Boc protected ester form for achiral and chiral building blocks. In the first stage of the synthesis, piperidine-4-carboxylic and (R)- and (S)-piperidine-3-carboxylic acids were converted to the corresponding β-keto esters, which were then treated with N,N-dimethylformamide dimethyl acetal. The subsequent reaction of β-enamine diketones with various N-mono-substituted hydrazines afforded the target 5-(N-Boc-piperidinyl)-1H-pyrazole-4-carboxylates as major products, and tautomeric NH-pyrazoles prepared from hydrazine hydrate were further N-alkylated with alkyl halides to give 3-(N-Boc-piperidinyl)-1H-pyrazole-4-carboxylates. The structures of the novel heterocyclic compounds were confirmed by 1H-, 13C-, and 15N-NMR spectroscopy and HRMS investigation.

Anwendung der 15N-NMR-Spektroskopie zur Charakterisierung reaktiver, koordinativ ungesättigter Zinn-, Bleiund Phosphor-Stickstoff-Verbindungen / Application of 15N-NMR Spectroscopy to the Characterization of Reactive, Coordinatively Unsaturated Tin-, Lead- and Phosphorus-Nitrogen Compounds

1987 ◽  
Vol 42 (12) ◽  
pp. 1515-1519 ◽  
Author(s):  
Carin Stader ◽  
Bernd Wrackmeyer
Keyword(s):  
Nmr Spectra ◽  
Pulse Sequence ◽  
Coupling Constants ◽  
Spin Coupling ◽  
15N Nmr ◽  
Nmr Data ◽  
15N Nmr Spectroscopy ◽  
Spin Coupling Constants ◽  
Spin Spin Coupling

AbstractThe basic INEPT pulse sequence proved most useful for recording 15N NMR spectra at natural abundance of bis(amino)stannvlenes (1). -plumbylenes (2) and of imino-amino-λ2-phosphanes (3), where the nitrogen atoms carry bulky substituents like Me3Si-, t-Bu-, 2.4.4-trimethyl-2- pentyl-groups (t-Oct-groups) or are part of the 2.2.6.6-tetramethylpiperidinyl group. The sensitiv­ity of this technique is proved by the observation of 117/119Sn or 207Pb satellites owing to spin-spin coupling constants 1J(117/119Sn15N) and 1J(117/119Pb15N), respectively. NMR data of bis[bis(trimethylsilyl)methyl]tin (4) are reported in order to corroborate the arguments for the interpretation of the δ(15N) and 1J(119Sn15N) data. The 15N NMR data of the λ2-phosphanes (3) indicate a bonding situation similar to that in triazenes.

Discovery and Biocatalytic Application of a PLP-Dependent Amino Acid γ-Substitution Enzyme that Catalyzes C-C Bond Formation

2020 ◽  
Author(s):  
Mengbin Chen ◽  
Chun-Ting Liu ◽  
Yi Tang
Keyword(s):  
Amino Acids ◽  
Biosynthetic Pathway ◽  
Pyridoxal Phosphate ◽  
Biochemical Characterization ◽  
Indole Alkaloid ◽  
Building Blocks ◽  
Nucleophilic Attack ◽  
Keto Esters ◽  
Key Enzyme

Pyridoxal phosphate (PLP)-dependent enzymes can catalyze various transformations of amino acids at alpha, beta, and gamma positions. These versatile enzymes are prominently involved in the biosynthesis of nonproteinogenic amino acids as building blocks of natural products, and are attractive biocatalysts. Here, we report the discovery of a two-step enzymatic synthesis of (2<i>S, </i>6<i>S</i>)-6-methyl pipecolate <b>1</b>, from the biosynthetic pathway of indole alkaloid citrinadin. The key enzyme CndF is PLP-dependent and catalyzes synthesis of (<i>S</i>)-2-amino-6-oxoheptanoate <b>3</b> that is in equilibrium with the cyclic Schiff base. The second enzyme CndE is a stereoselective imine reductase that gives <b>1</b>. Biochemical characterization of CndF showed this enzyme performs gamma-elimination of <i>O</i>-acetyl L-homoserine to generate the vinylglycine ketimine, which is subjected to nucleophilic attack by acetoacetate to form the new C<sub>gamma</sub>-C<sub>delta</sub> bond in <b>3 </b>and complete the gamma-substitution reaction. CndF displays substrate promiscuity towards different beta-keto carboxylate and esters. Using a recombinant <i>Aspergillus </i>strain expressing CndF and CndE, feeding various alkyl-beta-keto esters led to the biosynthesis of 6-substituted L-pipecolates. The discovery of CndF expands the repertoire of reactions that can be catalyzed by PLP-dependent enzymes.

Application of Reverse Two-Dimensional 1H{15N} NMR Spectroscopy to the Characterization of Two Inorganic Compounds:

1987 ◽  
Vol 42 (6) ◽  
pp. 703-706 ◽  
Author(s):  
Bernd Wrackmeyer ◽  
Klaus Schamel ◽  
Karlheinz Guldner ◽  
Max Herberhold
Keyword(s):  
Nmr Spectroscopy ◽  
Chemical Shifts ◽  
Inorganic Compounds ◽  
Ring System ◽  
Coupling Constants ◽  
15N Nmr ◽  
Two Dimensional ◽  
Hydrogen Atoms ◽  
15N Nmr Spectroscopy

AbstractThe inorganic ring system linked to the [Cr(CO)5] fragment [R = tBu (1), NH2 (2)], has been studied by reverse two-dimensional, 2D, 1H{15N} NMR spectroscopy. In solution, the exchange of the N-H hydrogen atoms is slow on the NMR time scale. Chemical shifts δ(1H), δ(13C), δ(31P), δ(15N) and coupling constants 1J(31P1H), 2J(31P13C), 1J(31P15N) are reported. In the case of 2, the reduced coupling constants 2K(31PN1H) and 1K(31P15N) have the same sign.

Alkoxyallenes as Starting Materials for the Syntheses of Natural Products

2020 ◽  
Vol 23 (27) ◽  
pp. 2976-3003 ◽  
Author(s):  
Volker Martin Schmiedel ◽  
Hans-Ulrich Reissig
Keyword(s):  
Natural Products ◽  
Carbonyl Compounds ◽  
Building Blocks ◽  
Alkyl Halides ◽  
Natural Product Synthesis ◽  
Subsequent Reaction ◽  
Enol Ethers ◽  
Carbocyclic Compounds ◽  
Nazarov Cyclizations ◽  
High Stereoselectivity

Alkoxyallenes are easily available and versatile building blocks for the preparation of a variety of natural products (terpenes, polyketides, alkaloids, amino acids, carbohydrates etc.) originating from different classes. The synthetic use of the three allene carbon atoms frequently follows the “normal” reactivity pattern showing that alkoxyallenes can be regarded as special enol ethers. Additions of alcohols or amines to alkoxyallenes form vinyl-substituted O,O- or N,O-acetals that are frequently used in ring-closing metathesis reactions. This methodology delivers crucial heterocyclic units of the target compounds. Enantioselective additions provide products with high enantiopurity. Alternatively, an “Umpolung” of reactivity of alkoxyallenes is achieved by lithiation at C-1 and subsequent reaction with electrophiles, such as alkyl halides, carbonyl compounds, imines or nitrones. High stereoselectivity of the addition step can be achieved by substrate control or auxiliary control. The high diastereo- or enantioselectivity is transferred to the subsequent acyclic or cyclic products. The cyclization of primary addition products occurs efficiently under mild conditions and provides functionalized dihydrofuran, dihydropyrrole or 1,2-oxazine derivatives. These are valuable intermediates for the synthesis of a variety of heterocyclic natural products. Nazarov cyclizations or gold catalyzed rearrangements allow the synthesis of five- and six-membered carbocyclic compounds that are also used for natural product synthesis. Dedicated to Dr. Reinhold Zimmer, a pioneer of alkoxyallene chemistry, on the occasion of his 60th birthday.

Discovery and Biocatalytic Application of a PLP-Dependent Amino Acid γ-Substitution Enzyme that Catalyzes C-C Bond Formation

2020 ◽  
Author(s):  
Mengbin Chen ◽  
Chun-Ting Liu ◽  
Yi Tang
Keyword(s):  
Amino Acids ◽  
Biosynthetic Pathway ◽  
Pyridoxal Phosphate ◽  
Biochemical Characterization ◽  
Indole Alkaloid ◽  
Building Blocks ◽  
Nucleophilic Attack ◽  
Keto Esters ◽  
Key Enzyme

Pyridoxal phosphate (PLP)-dependent enzymes can catalyze various transformations of amino acids at alpha, beta, and gamma positions. These versatile enzymes are prominently involved in the biosynthesis of nonproteinogenic amino acids as building blocks of natural products, and are attractive biocatalysts. Here, we report the discovery of a two-step enzymatic synthesis of (2<i>S, </i>6<i>S</i>)-6-methyl pipecolate <b>1</b>, from the biosynthetic pathway of indole alkaloid citrinadin. The key enzyme CndF is PLP-dependent and catalyzes synthesis of (<i>S</i>)-2-amino-6-oxoheptanoate <b>3</b> that is in equilibrium with the cyclic Schiff base. The second enzyme CndE is a stereoselective imine reductase that gives <b>1</b>. Biochemical characterization of CndF showed this enzyme performs gamma-elimination of <i>O</i>-acetyl L-homoserine to generate the vinylglycine ketimine, which is subjected to nucleophilic attack by acetoacetate to form the new C<sub>gamma</sub>-C<sub>delta</sub> bond in <b>3 </b>and complete the gamma-substitution reaction. CndF displays substrate promiscuity towards different beta-keto carboxylate and esters. Using a recombinant <i>Aspergillus </i>strain expressing CndF and CndE, feeding various alkyl-beta-keto esters led to the biosynthesis of 6-substituted L-pipecolates. The discovery of CndF expands the repertoire of reactions that can be catalyzed by PLP-dependent enzymes.

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