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Beilstein Journal of Organic Chemistry
Journal Prestige (SJR): 0.929

Citation Impact (citeScore): 2
Number of Followers: 15

This is an Open Access Journal

Open Access journal
ISSN (Print) 1860-5397
Published by Beilstein-Institut

[2 journals]

Functions of enzyme domains in 2-methylisoborneol biosynthesis and
enzymatic synthesis of non-natural analogs
- Authors: Binbin Gu; Lin-Fu Liang Jeroen S. Dickschat
  Abstract: Two aspects of the biosynthesis of the non-canonical terpene synthase for 2-methylisoborneol have been studied. Several 2-methylisoborneol synthases have a proline-rich N-terminal domain of unknown function. The results presented here demonstrate that this domain leads to a reduced enzyme activity, in addition to its ability to increase long-term solubility of the protein. Furthermore, the substrate scope of the 2-methylisoborneol synthase was investigated through enzyme incubations with several substrate analogs, giving access to two C12 monoterpenoids. Implications on the stereochemical course of the terpene cyclisation by 2-methylisoborneol synthase are discussed.
  Keywords: biosynthesis; enzymes; isotopes; substrate analogs; terpenes
  Citation: Beilstein Journal of Organic Chemistry 2023 19:104
  PubDate: Fri, 22 Sep 2023 10:30:00 GMT
  DOI: 10.3762/bjoc.19.104
α-(Aminomethyl)acrylates as acceptors in radical–polar crossover
1,4-additions of dialkylzincs: insights into enolate formation and
trapping
- Authors: Angel Palillero-Cisneros; Paola G. Gordillo-Guerra, Fernando García-Alvarez, Olivier Jackowski, Franck Ferreira, Fabrice Chemla, Joel L. Terán Alejandro Perez-Luna
  Abstract: We demonstrate that α-(aminomethyl)acrylates are suitable acceptors for 1,4-additions of dialkylzincs in aerobic conditions. The air-promoted radical–polar crossover process involves the 1,4-addition of an alkyl radical followed by homolytic substitution at the zinc atom of dialkylzinc. Coordination of the nitrogen atom to zinc enables this SH2 process which represents a rare example of alkylzinc-group transfer to a tertiary α-carbonyl radical. The zinc enolate thus formed readily undergoes β-fragmentation unless it is trapped by electrophiles in situ. Enolates of substrates having free N–H bonds undergo protodemetalation to provide ultimately the 1,4-addition adduct. In the presence of carbonyl acceptors, aldol condensation occurs providing overall a tandem 1,4-addition–aldol process. When a tert-butanesulfinyl moiety is present on the nitrogen atom, these electrophilic substitution reactions occur with good levels of chiral induction, paving the way to enantioenriched β2-amino acids and β2,2-amino acids.
  Keywords: β-amino acids; tandem reactions; radical–polar crossover; tert-butanesulfinamide; zinc radical transfer
  Citation: Beilstein Journal of Organic Chemistry 2023 19:103
  PubDate: Thu, 21 Sep 2023 11:31:00 GMT
  DOI: 10.3762/bjoc.19.103
Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in
organic synthesis: a review
- Authors: Nosheen Beig; Varsha Goyal Raj K. Bansal
  Abstract: N-Heterocyclic carbenes (NHCs) are a special type of carbenes in which the carbene carbon atom is part of the nitrogen heterocyclic ring. Due to the simplicity of their synthesis and the modularity of their stereoelectronic properties, NHCs have unquestionably emerged as one of the most fascinating and well-known species in chemical science. The remarkable stability of NHCs can be attributed to both kinetic as well as thermodynamic effects caused by its structural features. NHCs constitute a well-established class of new ligands in organometallic chemistry. Although initially NHCs were regarded as pure σ-donor ligands, later experimental and theoretical studies established the presence of a significant back donation from the d-orbital of the metal to the π* orbital of the NHC. Over the last two decades, NHC–metal complexes have been extensively used as efficient catalysts in different types of organic reactions. Of these, NHC–Cu(I) complexes found prominence for various reasons, such as ease of preparation, possibility of structural diversity, low cost, and versatile applications. This article overviews applications of NHC–Cu(I) complexes as catalysts in organic synthesis over the last 12 years, which include hydrosilylation reactions, conjugate addition, [3 + 2] cycloaddition, A3 reaction, boration and hydroboration, N–H and C(sp2)–H carboxylation, C(sp2)–H alkenylation and allylation, C(sp2)–H arylation, C(sp2)–H amidation, and C(sp2)–H thiolation. Preceding the section of applications, a brief description of the structure of NHCs, nature of NHC–metal bond, and methods of preparation of NHC–Cu complexes is provided.
  Keywords: conjugate addition; [3 + 2] cycloaddition reaction; hydrosilylation reaction; N-heterocyclic carbenes; NHC–Cu complexes; NHC–Cu complexes as catalyst
  Citation: Beilstein Journal of Organic Chemistry 2023 19:102
  PubDate: Wed, 20 Sep 2023 09:29:00 GMT
  DOI: 10.3762/bjoc.19.102
One-pot nucleophilic substitution–double click reactions of biazides
leading to functionalized bis(1,2,3-triazole) derivatives
- Authors: Hans-Ulrich Reissig; Fei Yu
  Abstract: The nucleophilic substitution of benzylic bromides with sodium azide was combined with a subsequent copper-catalyzed (3 + 2) cycloaddition with terminal alkynes. This one-pot process was developed with a simple model alkyne, but then applied to more complex alkynes bearing enantiopure 1,2-oxazinyl substituents. Hence, the precursor compounds 1,2-, 1,3- or 1,4-bis(bromomethyl)benzene furnished geometrically differing bis(1,2,3-triazole) derivatives. The use of tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine (TBTA) as ligand for the click step turned out to be very advantageous. The compounds with 1,2-oxazinyl end groups can potentially serve as precursors of divalent carbohydrate mimetics, but the reductive cleavage of the 1,2-oxazine rings to aminopyran moieties did not proceed cleanly with these compounds.
  Keywords: alkynes; azides; copper catalysis; nucleophilic substitution; 1,2-oxazines
  Citation: Beilstein Journal of Organic Chemistry 2023 19:101
  PubDate: Mon, 18 Sep 2023 12:53:00 GMT
  DOI: 10.3762/bjoc.19.101
Functional characterisation of twelve terpene synthases from
actinobacteria
- Authors: Anuj K. Chhalodia; Houchao Xu, Georges B. Tabekoueng, Binbin Gu, Kizerbo A. Taizoumbe, Lukas Lauterbach Jeroen S. Dickschat
  Abstract: Fifteen type I terpene synthase homologs from diverse actinobacteria that were selected based on a phylogenetic analysis of more than 4000 amino acid sequences were investigated for their products. For four enzymes with functions not previously reported from bacterial terpene synthases the products were isolated and their structures were elucidated by NMR spectroscopy, resulting in the discovery of the first terpene synthases for (+)-δ-cadinol and (+)-α-cadinene, besides the first two bacterial (−)-amorpha-4,11-diene synthases. For other terpene synthases with functions reported from bacteria before the products were identified by GC–MS. The characterised enzymes include a new epi-isozizaene synthase with monoterpene synthase side activity, a 7-epi-α-eudesmol synthase that also produces hedycaryol and germacrene A, and four more sesquiterpene synthases that produce mixtures of hedycaryol and germacrene A. Three phylogenetically related enzymes were in one case not expressed and in two cases inactive, suggesting pseudogenisation in the respective branch of the phylogenetic tree. Furthermore, a diterpene synthase for allokutznerene and a sesterterpene synthase for sesterviolene were identified.
  Keywords: actinomycetes; biosynthesis; enzymes; NMR spectroscopy; terpenes
  Citation: Beilstein Journal of Organic Chemistry 2023 19:100
  PubDate: Fri, 15 Sep 2023 10:15:00 GMT
  DOI: 10.3762/bjoc.19.100
Consecutive four-component synthesis of trisubstituted 3-iodoindoles by an
alkynylation–cyclization–iodination–alkylation sequence
- Authors: Nadia Ledermann; Alae-Eddine Moubsit Thomas J. J. Müller
  Abstract: A library of 19 differently substituted 3-iodoindoles is generated by a consecutive four-component reaction starting from ortho-haloanilines, terminal alkynes, N-iodosuccinimide, and alkyl halides in yields of 11–69%. Initiated by a copper-free alkynylation, followed by a base-catalyzed cyclizive indole formation, electrophilic iodination, and finally electrophilic trapping of the intermediary indole anion with alkyl halides provides a concise one-pot synthesis of 3-iodoindoles. The latter are valuable substrates for Suzuki arylations, which are exemplified with the syntheses of four derivatives, some of them are blue emitters in solution and in the solid state, in good yield.
  Keywords: alkynylation; catalysis; cyclization; indoles; iodination; multicomponent reactions
  Citation: Beilstein Journal of Organic Chemistry 2023 19:99
  PubDate: Thu, 14 Sep 2023 10:17:00 GMT
  DOI: 10.3762/bjoc.19.99
Visible-light-induced nickel-catalyzed α-hydroxytrifluoroethylation of
alkyl carboxylic acids: Access to trifluoromethyl alkyl acyloins
- Authors: Feng Chen; Xiu-Hua Xu, Zeng-Hao Chen, Yue Chen Feng-Ling Qing
  Abstract: A visible-light-induced nickel-catalyzed cross coupling of alkyl carboxylic acids with N-trifluoroethoxyphthalimide is described. Under purple light irradiation, an α-hydroxytrifluoroethyl radical generated from a photoactive electron donor–acceptor complex between Hantzsch ester and N-trifluoroethoxyphthalimide was subsequently engaged in a nickel-catalyzed coupling reaction with in situ-activated alkyl carboxylic acids. This convenient protocol does not require photocatalysts and metal reductants, providing a straightforward and efficient access to trifluoromethyl alkyl acyloins in good yields with broad substrate compatibility. The complex bioactive molecules were also compatible with this catalytic system to afford the corresponding products.
  Keywords: alkyl carboxylic acids; cross coupling; EDA complex; nickel catalysis; trifluoromethyl acyloins
  Citation: Beilstein Journal of Organic Chemistry 2023 19:98
  PubDate: Mon, 11 Sep 2023 13:55:00 GMT
  DOI: 10.3762/bjoc.19.98
Synthesis of ether lipids: natural compounds and analogues
- Authors: Marco Antônio G. B. Gomes; Alicia Bauduin, Chloé Le Roux, Romain Fouinneteau, Wilfried Berthe, Mathieu Berchel, Hélène Couthon Paul-Alain Jaffrès
  Abstract: Ether lipids are compounds present in many living organisms including humans that feature an ether bond linkage at the sn-1 position of the glycerol. This class of lipids features singular structural roles and biological functions. Alkyl ether lipids and alkenyl ether lipids (also identified as plasmalogens) correspond to the two sub-classes of naturally occurring ether lipids. In 1979 the discovery of the structure of the platelet-activating factor (PAF) that belongs to the alkyl ether class of lipids increased the interest in these bioactive lipids and further promoted the synthesis of non-natural ether lipids that was initiated in the late 60’s with the development of edelfosine (an anticancer drug). More recently, ohmline, a glyco glycero ether lipid that modulates selectively SK3 ion channels and reduces in vivo the occurrence of bone metastases, and other glyco glycero ether also identified as GAEL (glycosylated antitumor ether lipids) that exhibit promising anticancer properties renew the interest in this class of compounds. Indeed, ether lipid represent a new and promising class of compounds featuring the capacity to modulate selectively the activity of some membrane proteins or, for other compounds, feature antiproliferative properties via an original mechanism of action. The increasing interest in studying ether lipids for fundamental and applied researches invited to review the methodologies developed to prepare ether lipids. In this review we focus on the synthetic method used for the preparation of alkyl ether lipids either naturally occurring ether lipids (e.g., PAF) or synthetic derivatives that were developed to study their biological properties. The synthesis of neutral or charged ether lipids are reported with the aim to assemble in this review the most frequently used methodologies to prepare this specific class of compounds.
  Keywords: amphiphiles; edelfosine; GAEL; glycerol lipids; glycolipids; ohmline; plasmalogen
  Citation: Beilstein Journal of Organic Chemistry 2023 19:96
  PubDate: Fri, 08 Sep 2023 09:26:00 GMT
  DOI: 10.3762/bjoc.19.96
Organic thermally activated delayed fluorescence material with strained
benzoguanidine donor
- Authors: Alexander C. Brannan; Elvie F. P. Beaumont, Nguyen Le Phuoc, George F. S. Whitehead, Mikko Linnolahti Alexander S. Romanov
  Abstract: Organic thermally activated delayed fluorescence (TADF) materials have been widely investigated due to their impressive electronic properties and applied potential for the third generation of organic light-emitting diodes (OLED). We present organic TADF material (4BGIPN) based on the strained benzoguanidine donor and compare it with the benchmark carbazole-based material (4CzIPN). Extended π-conjugation in 4BGIPN material results in yellow-green luminescence at 512 nm with a fast radiative rate of 5.5 × 10−5 s−1 and a photoluminescence quantum yield of 46% in methylcyclohexane solution. Such a nitrogen-rich 4BGIPN material has a significantly stabilized highest occupied molecular orbital (HOMO) at −6.4 eV while the lowest unoccupied molecular orbital (LUMO) at −4.0 eV, indicating potential suitability for application as the electron transport layer or TADF class III emitter in OLEDs.
  Keywords: guanidine; organic; photoluminescence; TADF; yellow
  Citation: Beilstein Journal of Organic Chemistry 2023 19:95
  PubDate: Thu, 07 Sep 2023 13:09:00 GMT
  DOI: 10.3762/bjoc.19.95
Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving
ether α-C(sp3)–H to construct C–C bonds
- Authors: Hui Yu; Feng Xu
  Abstract: Ether derivatives are widespread as essential building blocks in various drugs, natural products, agrochemicals, and materials. Modern economy requires developing green strategies with improved efficiency and reduction of waste. Due to its atom and step-economy, the cross-dehydrogenative coupling (CDC) reaction has become a major strategy for ether functionalization. This review covers C–H/C–H cross-coupling reactions of ether derivatives with various C–H bond substrates via non-noble metal catalysts (Fe, Cu, Co, Mn, Ni, Zn, Y, Sc, In, Ag). We discuss advances achieved in these CDC reactions and hope to attract interest in developing novel methodologies in this field of organic chemistry.
  Keywords: alkylation; cross-dehydrogenation coupling; ether; non-noble metals
  Citation: Beilstein Journal of Organic Chemistry 2023 19:94
  PubDate: Wed, 06 Sep 2023 13:50:00 GMT
  DOI: 10.3762/bjoc.19.94