Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• observed (yield = 72%) with analysis by chiral HPLC revealing no erosion of the enantiomeric ratio (er = 99:1). At this stage, the suitability of BT-SCF3-mediated deoxyfluorination for the one-pot formation of peptide linkages between amino acids was investigated (Scheme 3). Treatment of N-Boc-valine under

• under mild and operationally simple conditions while peptide coupling between two amino acids could be efficiently conducted using the longer-chain perfluoroalkyl reagent BT-SC5F11. Mechanistic studies revealed that each equivalent of the benzothiazolium reagent can feasibly generate two equivalents of

• fluoride derivatives. Reactions conducted on a 0.5 mmol scale, isolated yields after column chromatography. One-pot BT-SCF3-mediated deoxygenative coupling of amino acids. Isolated yields after column chromatography. Plausible mechanism for the deoxyfluorination of carboxylic acids with BT-SCF3

Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• , likely acting as its proximal ligand. As described above, the H73A Vs NnlA variant lacked NNG degradation activity and had reduced iron content [21]. The AlphaFold model also predicts a distal pocket composed of Tyr99, Ala101, Ile109, Val111, and Gln127. These amino acids are conserved in an alignment of

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

•  1). Results and Discussion Syntheses of C60–oligopeptides 5a–c The oligopeptides 2a–c were synthesized on resin using Fmoc-protected amino acids with a standard SPPS method (Figure 1a) [43]. A moderate loading (0.4 mmol⋅g−1) of the initial amino acid was used. After synthesizing the pentamer of Lys

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• , resulting in daptomycin (12) formation with a ratio of cyclization to hydrolysis of 3:1 (Scheme 4a). The significance of single amino acids for daptomycin bioactivity was evaluated, for instance, the substitution of ʟ-3-MeGlu12 by ʟ-Glu12 in Dap yielded a 7-fold increase of the MIC against B. subtilis

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• multicomponent reaction protocol. Keywords: carboamination; diazo chemistry; palladium catalysis; radical-polar crossover; three-component reaction; Introduction Since the discovery of the existence of non-canonical amino acids (AAs) in organisms, such structural motifs have attracted considerable attention

Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• terpenoid moiety is held in a substrate pocket consisting of hydrophobic amino acids, and the polyketide moiety is retained by a loop structure serving as a lid. The conformation of the terpenoid moiety can be easily altered by mutations to the enzyme’s substrate retention site, thereby changing the

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• (SORHA), Triticum aestivum (TRZAS), and Zea mays (ZEAMX). LpFAT A expression and purification: The fat a03 gene from Lemna paucicostata, in which the N-terminal amino acids representing the chloroplast transit peptide were replaced by an N-terminal 6xHis-tag, was cloned into a pET24 vector [3]. The LpFAT

A new analog of dihydroxybenzoic acid from Saccharopolyspora sp. KR21-0001

• Rattiya Janthanom,
• Yuta Kikuchi,
• Hiroki Kanto,
• Tomoyasu Hirose,
• Arisu Tahara,
• Takahiro Ishii,
• Arinthip Thamchaipenet and
• Yuki Inahashi

Beilstein J. Org. Chem. 2024, 20, 497–503, doi:10.3762/bjoc.20.44

• HCl. The obtained amino acid (alanine) and authentic amino acids were modified using Nα-(5-fluoro-2,4-dinitrophenyl)-ᴅ-leucinamide (ᴅ-FDLA). The LC–MS analysis of ᴅ-FDLA derivatives revealed that the chiral center of the amino acid in 1 had ʟ configuration (Figure S7, Supporting Information File 1

• . Advanced Marfey’s analysis A volume of 20 µL of 1 M NaHCO3 was added to each 50 µL of the hydrolysate of the de-sulfurized derivative of 1 and 1 mM standard amino acids (ʟ- and ᴅ-alanine). Then, 50 µL of ᴅ-FDLA (10 mg·mL−1 in acetone) was added to the mixtures and mixed well (the color changed from yellow

Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

• Fumihiro Ishikawa,
• Sho Konno,
• Hideaki Kakeya and
• Genzoh Tanabe

Beilstein J. Org. Chem. 2024, 20, 445–451, doi:10.3762/bjoc.20.39

• (Figure 1) [3]. The adenylation (A) domain in NRPSs is responsible for the selection and activation of amino acids, hydroxy acids, and aryl acids upon ATP consumption (Figure 2a) [4]. The activated aminoacyladenosine monophosphate (AMP) is transferred to the thiol group of a phosphopantetheine prosthetic

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• with aryl thiols [70]. Further studies showed that 4-(trifluoromethyl)thiophenol (97) could act as a catalytic reductant in the aminodecarboxylation reaction of NHPI esters derived from α-amino acids [71] (Scheme 19). Accordingly, visible light irradiation of a mixture consisting of N-Boc-alanine NHPI

• forming an iminium intermediate 101. Finally, nucleophilic addition of phthalimide anion 102 afforded the amination product 103. Bosque and Bach reported the use of 3-acetoxyquinuclidine (q-Ac) as a catalytic donor for the activation of TCNHPI esters derived from α-amino acids [72] (Scheme 20). Treatment

• reported in recent years, including decarboxylative alkynylations [76][77][78] and the C(sp3)–H alkylation of α-amino acids [79]. The ability of NHPI esters to act as dual reagents was also investigated by Glorius and co-workers in the context of a photoinduced Pd-catalyzed aminoalkylation of 1,4-dienes

Discovery of unguisin J, a new cyclic peptide from Aspergillus heteromorphus CBS 117.55, and phylogeny-based bioinformatic analysis of UngA NRPS domains

• Sharmila Neupane,
• Marcelo Rodrigues de Amorim and
• Elizabeth Skellam

Beilstein J. Org. Chem. 2024, 20, 321–330, doi:10.3762/bjoc.20.32

• heptapeptides isolated predominantly from Aspergillus sp. [1][2][3][4][5][6][7][8]. Distinctive features of these cyclic peptides include the non-proteinogenic amino acid γ-aminobutyric acid (GABA) and the incorporation of up to five ᴅ-amino acids (Figure 1) [1][2][3][4][5][6][7][8]. The amino acids at

• positions 1 (ᴅ-Ala) and 7 (GABA) are conserved but there is considerable variability at positions 2–6, including the incorporation of additional non-proteinogenic amino acids β-methylphenylalanine (βMePhe) and kynurenine (Kyn) [3][4]. So far, no significant biological activities have been reported for these

• bond formation. Additional common domains include epimerization (E) domains for converting naturally occurring ʟ-amino acids to ᴅ-amino acids, methyltransferase (MT) domains that typically methylate specific N atoms, and terminal condensation (CT) domains which cyclize the growing peptide chain and

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• amino acids and is predicted to fold into two linked β-trefoil domains belonging to carbohydrate-binding module family 13 (CBM13) and placing it into the group of R-type lectins. Both CBM13 domains are likely to exhibit carbohydrate-binding activity due to the conservation of key amino acids in at least

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• compatibility and efficiency of a diverse range of redox-active esters 3, deriving from various aliphatic carboxylic acids (including primary, secondary, and tertiary acids), as well as α-amino acids. Impressively, these redox-active esters exhibited exceptional compatibility, high effectiveness, and remarkable

• -anion catalysis under visible light irradiation, as depicted in Scheme 9. Subsequent investigations revealed that redox-active esters 3 and Katritzky salts 15 derived from amino acids could be effectively employed in decarboxylative/deaminative cross-coupling reactions [15]. These reactions enabled the

• route for the synthesis of unnatural amino acids and amines. Remarkably, the procedure exhibited excellent compatibility with a wide range of alkyl radicals, including primary, secondary, tertiary, and α-heterosubstituted radicals generated from corresponding redox-active esters 3. Concurrently, Shang

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• acid-catalyzed hydrocyanation of trifluoromethylated acylhydrazones, in which the product was the precursor for the preparation of chiral fluorinated amino acids [104] (Scheme 17a). Meanwhile, Hu et al. provided a novel and efficient process for the synthesis of polysubstituted 3-trifluoromethyl-1,2,4

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• Pharmacy, Changzhou University, Changzhou 213164, China 10.3762/bjoc.19.123 Abstract The [3 + 2] cycloadditions of stabilized azomethine ylides (AMYs) derived from amino esters are well-established. However, the reactions of semi-stabilized AMYs generated from decarboxylative condensation of α-amino acids

• with arylaldehydes are much less explored. The [3 + 2] adducts of α-amino acids could be used for a second [3 + 2] cycloaddition as well as for other post-condensation modifications. This article highlights our recent work on the development of α-amino acid-based [3 + 2] cycloaddition reactions of N–H

• aldehydes and α-amino esters (via dehydration) or α-amino acids (via decarboxylation) could be classified based on the substitution groups on the N atom to: 1) N-substituted (N–R type), 2) hydrogen containing (N–H type), and 3) metal complexes (N–M type) (Figure 1) [16][17]. These AMYs could also be

Tying a knot between crown ethers and porphyrins

• Maksym Matviyishyn and
• Bartosz Szyszko

Beilstein J. Org. Chem. 2023, 19, 1630–1650, doi:10.3762/bjoc.19.120

• by exploiting them for molecular recognition (Figure 16A). The dual nature of hybrids offers promising prospects, with a coordination pocket enabling selective binding of organic molecules such as natural and non-natural amino acids, hormones, neurotransmitters and other biomolecules. In such

Complexes of resorcin[4]arene with secondary amines: synthesis, solvent influence on “in-out” structure, and theoretical calculations of non-covalent interactions

• Waldemar Iwanek

Beilstein J. Org. Chem. 2023, 19, 1525–1536, doi:10.3762/bjoc.19.109

• ], amino alcohols [10], and amino acids [11] have been studied due to their potential applications in supramolecular chemistry, drug delivery, and molecular recognition. The complexation of R[4]A with amines is based on the formation of hydrogen bonds between the hydroxy groups of the resorcinol units and

Functions of enzyme domains in 2-methylisoborneol biosynthesis and enzymatic synthesis of non-natural analogs

• Binbin Gu,
• Lin-Fu Liang and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 1452–1459, doi:10.3762/bjoc.19.104

• different organisms can have a variable lengths ranging from ca. 330 amino acids (e.g., in Longispora albida DSM 44784, accession number WP_018349754, 329 amino acids) to more than 550 amino acids (e.g., in Nocardia amikacinitolerans DSM 45535, accession number WP_253814817, 580 amino acids). The long

α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• 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; Introduction Dialkylzinc reagents react in aerobic medium with a range of α,β-unsaturated

• view, the reported protocols are relevant as they offer a new, direct and modular route to enantioenriched α-mono- and α,α-disubstituted β-amino acids (β2-amino acids and β2,2-amino acids), with, for the latter, the noteworthy stereocontrolled construction of an all-carbon quaternary stereocenter

• . Furthermore, our protocol provides a complement to existing literature, as none of the previously reported methods to convert α-(aminomethyl)acrylates into enantioenriched β-amino acids is applicable for the preparation of β2,2-amino acids [27][28][29][30][31]. Experimental 1. Procedure for the monoallylation

Visible-light-induced nickel-catalyzed α-hydroxytrifluoroethylation of alkyl carboxylic acids: Access to trifluoromethyl alkyl acyloins

• Feng Chen,
• Xiu-Hua Xu,
• Zeng-Hao Chen,
• Yue Chen and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2023, 19, 1372–1378, doi:10.3762/bjoc.19.98

• challenging, and to the best of our knowledge, only Kawase's group [26] reported the preparation of such compounds starting from α-hydroxy acids or α-amino acids in the presence of trifluoroacetic anhydride and pyridine with very limited substrate scope (Scheme 1c). Therefore, the development of a more

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• –Crafts reaction. Reaction between indoles and racemic 2,3-dihydroisoxazol-3-ol derivatives. Exploiting 5-aminoisoxazoles as nucleophiles. Reaction between unsubstituted indoles and 3-alkynylated 3-hydroxy-1-oxoisoindolines. Synthesis of unnatural amino acids bearing an aza-quaternary stereocenter

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• requires a multistep process in conventional chemical synthesis [39][40][41]. Among the various widely available and abundant substrates for photocatalyzed reactions, natural and unnatural α-amino acids play a very important role, given their paramount importance across several chemistry fields as well as

• their ability to participate in either redox step of the catalytic cycle [42][43][44][45]. For example, the main use of α-amino acids in syntheses via photoredox catalysis is as readily available precursors of regioselective α-amino radicals by decarboxylative transformations, by oxidation of the

• carboxylate anion and/or reduction of the corresponding N-hydroxyphthalimide- (NHPI)-derived redox-active ester, although it destroys their stereochemical information [46][47][48][49][50][51]. In addition, the side-chains of aromatic amino acids (mainly electron-rich tryptophan and tyrosine) can be

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• functionalizations under ligand-controlled conditions are underexplored. Hence, differentiating from this co-coordinative model, in 2013, Zeng and co-workers [86] reported the MPAA (mono-N-protected amino acids) ligand-promoted non-chelate-assisted C–H activation via Pd-catalyzed dehydrogenative Heck reactions on

Palladium-catalyzed enantioselective three-component synthesis of α-arylglycine derivatives from glyoxylic acid, sulfonamides and aryltrifluoroborates

• Bastian Jakob,
• Nico Schneider,
• Luca Gengenbach and
• Georg Manolikakes

Beilstein J. Org. Chem. 2023, 19, 719–726, doi:10.3762/bjoc.19.52

• products. Keywords: amino acids; asymmetric catalysis; multicomponent reaction; palladium catalysis; Petasis reaction; sulfonamides; Introduction α-Amino acids play a crucial role in every aspect of our human life [1]. They are important synthetic intermediates in the chemical industry and used for the

• production of drugs, fertilizers, (biodegradable) polymers or nutritional supplements [2]. More importantly, α-amino acids form the backbone of all proteins and enzymes are therefore essential for almost all biological processes. In the last twenty years non-proteinogenic and chemically synthesized unnatural

• amino acids received increasing attention due to advances in protein-engineering and the development of protein-based therapeutics [3][4]. Among the different types of non-proteinogenic and unnatural amino acids, α-arylglycines play a particular important role. The arylglycine scaffold can be found in