(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• , respectively (Scheme 12B) [58]. Saponification of the ester moieties in these species followed by Curtius rearrangements then led to amines 114 and 116. Non-natural amino acid derivatives 113 and 117 are intermediates prepared using these methods that could be of interest to medicinal chemistry. Alcohol 111

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

• -light-mediated palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines, affording unsaturated γ- and ε-amino acid derivatives with diverse structures. In this methodology, the diazo compound readily transforms into a hybrid α-ester

• diverse derivatizations further highlight the practical utility of this MCR protocol. Background (a and b) and proposed carboamination MCR with diazo esters (c). a) Selected bioactive γ- and ε-amino acid derivatives. b) Multicomponent reaction strategies with diazo compounds. c) Our design: a radical MCR

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

• as H-bond donor to the catalyst (see transition state 97, Scheme 22a) [51]. Recently, the same research group documented another aza-Friedel–Crafts reaction between indoles 4 and 95 that frames aza-quaternary stereocenter at the α-carbon of unnatural amino acid derivatives 96. Enantiocontrol was

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• between the o-phenylene fragment and the benzyl moiety in the proline. The stronger the π-stacking interactions are, the more rigid are the complexes and the higher is the difference in the relative energies of the amino acid derivatives with different configuration of the α-stereocenter. As it has been

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• radical anions influenced by substituents in the cyclopropane ring are discussed. Optimization of the reaction conditions opens a route to the non-proteinogenic amino acid derivatives containing an α–β or β–γ double C=C bond in the side chain; the regioselectivity can be tuned by the addition of Lewis

• include disproportionation reaction yielding a mixture of alkenes and the corresponding hydrogenated derivatives, intramolecular cyclization and reaction with external electrophiles. Optimization of the reaction conditions opens a route to amino acid derivatives containing the α-β or β-γ double C=C bond

• in the side chain; the regioselectivity can be tuned by the addition of Lewis acids. This type of non-proteinogenic amino acid derivatives is not easily available but strongly required due to their bioactivity. One-pot nucleophilic in situ functionalization of the double bond of dehydroalanine

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• moderate yields (37–63%), and a decreased yield was observed with an increase of the aliphatic chain length, which was more accentuated for the diacid derivatives, and more subtle for the amino acid derivatives (Scheme 30). The same methodology was applied during the synthesis of oligopeptides linked to 10

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• as a pro-nucleophile in an enantioselective addition reaction. The mild reaction conditions allow the use of various functionalized malonamates. Given the importance of highly functionalized α-amino acid derivatives, the present strategy could be useful in generating a wide range of α-oxyamino

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• widely used as building blocks to prepare various heterocyclic peptides [17][18][19][20][21][22]. In particular, 1,2-oxazole amino acid derivatives, such as compounds V [20], VI [21], and VII, VIII [22], can be easily synthesized and are suitable for insertion with the corresponding heterocycle into a

• their syn- and anti-orientation is present in the molecule [45][46]. Ley et al. demonstrated that selective chemical exchange NMR experiments are very useful in the determination of equilibrating rotamers, including chiral N-Boc amino acid derivatives, from non-equilibrating diastereomers [47]. Chemical

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

• İlknur Polat,
• Selçuk Eşsiz,
• Uğur Bozkaya and
• Emine Salamci

Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7

• β-amino acid derivatives have antibiotic (oryzoxymycin) and antifungal activities (Figure 1) [12][13]. Among the cyclic β-amino acids, the most widely investigated derivatives are the five- and six-membered derivatives [8][9][10][14][15], but only a few synthetic methods are available for the

• -hydroxylated cyclooctane amino acids [14][18]. Also in other ring systems, only non-hydroxylated cyclic amino acids and derivatives were synthesized [8][9][10][15][16]. Therefore, we were inspired to develop new methods for the synthesis of hydroxylated β-amino acid derivatives containing eight-membered rings

• . We have recently reported the synthesis of various eight-membered aminocyclitols and their derivatives [19][20][21][22][23][24][25]. In the present paper, we describe the synthesis of some hydroxylated β-amino acid derivatives containing eight-membered rings starting from cis,cis-1,3-cyclooctadiene

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• proton of the enolizable β-ketoester 49 and thus activating the nucleophilic species. This enolate then adds to the cationic substrate from in situ upon halide abstraction of α-chloro amino acid derivatives 48 by the thiourea moiety of the bifunctional catalyst (Scheme 10c, key intermediate), leading to

• have been provided by the group of Jacobsen in the nucleophilic addition of indoles 17 to pyranones 62 (Scheme 14a) [71], as well as in the enantioselective synthesis of α-allyl amino esters 67 by the reaction of α-chloro amino acid derivatives 65 with allyltin and allylsilane 66 nucleophiles [72

Enantioenriched α-substituted glutamates/pyroglutamates via enantioselective cyclopropenimine-catalyzed Michael addition of amino ester imines

• Zara M. Seibel,
• Jeffrey S. Bandar and
• Tristan H. Lambert

Beilstein J. Org. Chem. 2021, 17, 2077–2084, doi:10.3762/bjoc.17.134

• strategy for the enanantioselective conjugate addition of amino acid derivatives for this reaction remains an unmet goal. Our group previously described a chiral cyclopropenimine catalyst that displayed outstanding reactivity for addition reactions of glycine imines [40][41]. We hypothesized that this

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• phosphono-PNAs retained the stability against nucleases. In another study, conjugation with glutamine phosphonate or lysine bis-phosphonate amino acid derivatives introduced up to twelve negative charges (phosphonate moieties) into PNAs [91]. The negative charges allowed cationic lipid-mediated delivery of

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• the main characteristics of C60 stimulated a great interest in the application of fullerenes in medical chemistry. Of the fullerene-based biologically significant molecules, amino acid derivatives are of particular interest. In fact, Prato and co-workers synthesized and characterized the first peptide

Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives

• Alexander Leslie,
• Thomas S. Moody,
• Megan Smyth,
• Scott Wharry and
• Marcus Baumann

Beilstein J. Org. Chem. 2021, 17, 379–384, doi:10.3762/bjoc.17.33

• after removal of BnOH, vide infra). The continuous flow set-up used. Side reaction during formation of product 3m. Flow set-up for the CALB-mediated impurity tagging approach. Strategies towards accessing β-amino acid derivatives 8. Complementary flow approaches towards the β-amino acid derivatives 8

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• insulin Schmuck and co-workers reported a supramolecular ensemble in combination of a pyrene-tagged amphiphilic peptide beacon (6) and a macrocyclic host (cucurbit[8]uril, CB[8]) for ratiometric fluorescent detection of amino acid derivatives, specific peptides, and proteins in aqueous media (Figure 6

• (TrpOMe, PheOMe, LeuOMe) these are found to be more active compared to other amino acid derivatives in displacing 6 from the CB[8] cavity. Similarly, peptides having a hydrophobic amino acid residue at the N-terminus also show a high displacement activity. Human insulin, having a rare Phe residue at the N

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• (Scheme 10). Notably, this reaction used an air and moisture-stable chiral palladium complex as the catalyst, which worked well at low catalyst loading (as low as 0.5 mol %). In 2015, Shi et al. [47] introduced a Pd(II)/Pd(IV)-catalyzed fluorination of β-methylene C(sp3)–H bonds of α-amino acid

• derivatives (Scheme 11a). This process was carried out under the strongly binding bidentate 2-(pyridine-2-yl)isopropylamine (PIP) auxiliary. A range of substrates containing both aliphatic and benzylic C(sp3)–H bonds was finally converted to the corresponding fluorinated products with excellent

Complexation of chiral amines by resorcin[4]arene sulfonic acids in polar media – circular dichroism and diffusion studies of chirality transfer and solvent dependence

• Bartosz Setner and
• Agnieszka Szumna

Beilstein J. Org. Chem. 2019, 15, 1913–1924, doi:10.3762/bjoc.15.187

• chemistry. In the present study we demonstrate that resorcin[4]arene sulfonic acid (RSA) interacts with chiral amines (amino acid derivatives and aminocavitands) to form inclusion complexes and capsules based on electrostatic interactions. The complexes were characterized by circular dichroism and DOSY NMR

• informative and reflect the thermodynamic stability of complexes. They also suggest that this technique may be suitable for estimation of the order of thermodynamic stability of the complexes using only a single-spectrum measurement. Assuming that the size of amino acid derivatives is roughly similar and

• NMR or UV/CD titrations, because complexation induces virtually no complexation-induced shifts nor UV/CD changes. Conclusion We have shown that resorcin[4]arene sulfonic acid (RSA) 1 is able to strongly interact with basic amino acid derivatives (LysOMe, ArgOMe, HisOMe) forming 1:2 complexes in

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• , perhaps because the α,β-unsaturated double bond affected the iodination. Mohan et al. successfully developed an efficient copper-catalyzed aerobic oxidative amination of C(sp3)–H bonds to synthesize imidazo[1,5-a]pyridine derivatives [122]. The reaction was also applicable to amino acid derivatives, as

Anomeric sugar boronic acid analogues as potential agents for boron neutron capture therapy

• Daniela Imperio,
• Erika Del Grosso,
• Silvia Fallarini,
• Grazia Lombardi and
• Luigi Panza

Beilstein J. Org. Chem. 2019, 15, 1355–1359, doi:10.3762/bjoc.15.135

• . Galactose and fructose also allow tumor growth in the absence of glucose. Boronic acid derivatives have gained interest in the last years in different fields such as the development of enzyme inhibitors, drug delivery polymers, saccharide sensors and as boron carriers for BNCT, e.g., amino acid derivatives

Synthesis of acylglycerol derivatives by mechanochemistry

• Karen J. Ardila-Fierro,
• Andrij Pich,
• Marc Spehr,
• José G. Hernández and
• Carsten Bolm

Beilstein J. Org. Chem. 2019, 15, 811–817, doi:10.3762/bjoc.15.78

• loads has led to mechanoenzymatic transformations [5][6][7], and to synthesize amino acid derivatives [8][9][10] and peptides [11][12][13] by ball milling and extrusion techniques. Similarly, mechanochemical derivatizations of sugars and sugar derivatives such as cyclodextrins (CDs) have proven

Solid-phase synthesis of biaryl bicyclic peptides containing a 3-aryltyrosine or a 4-arylphenylalanine moiety

• Iteng Ng-Choi,
• Àngel Oliveras,
• Lidia Feliu and
• Marta Planas

Beilstein J. Org. Chem. 2019, 15, 761–768, doi:10.3762/bjoc.15.72

• peptidyl resin precursor containing the required boronate and halogenated amino acid derivatives followed by its cyclization through the formation of an aryl–aryl bond between these two amino acids via a Suzuky–Miyaura reaction. It is worthwhile to mention that both the borylation and the cross-coupling

Dirhodium(II)-catalyzed [3 + 2] cycloaddition of N-arylaminocyclopropane with alkyne derivatives

• Wentong Liu,
• Yi Kuang,
• Zhifan Wang,
• Jin Zhu and
• Yuanhua Wang

Beilstein J. Org. Chem. 2019, 15, 542–550, doi:10.3762/bjoc.15.48

• method has potential synthetic practicality by providing a convenient way to synthesize trans-cyclic β-amino acid derivatives. Further application of this method with other cycloaddition partners and asymmetric synthesis of the chiral ring with the help of chiral auxiliaries are currently underway

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• , various alkyl substituents could be present at the propargylic position in glycolates 64k–n which afforded the corresponding rearranged compounds 66k–n in moderate yields (40–61%, Scheme 23) [65]. With the goal of accessing α-amino acid derivatives incorporating an alkylidenecyclopropane, the Ireland

• synthesis of a wide variety of alkylidenecyclopropanes, substituted by heteroatoms (P, O, N, F) and/or incorporating valuable functional groups (α-alkoxy or α-amino acid derivatives) which are potentially useful for further functionalization. The reactivity of heterosubstituted/functionalized

Cross metathesis-mediated synthesis of hydroxamic acid derivatives

• Shital Kumar Chattopadhyay,
• Subhankar Ghosh and
• Suman Sil

Beilstein J. Org. Chem. 2018, 14, 3070–3075, doi:10.3762/bjoc.14.285

• ], separately. Fortunately, both the reactions proceeded well and the desired amino acid derivatives 7k and 7l were obtained in good yields after hydrogenation. Conclusion In conclusion, we have developed a direct access to functionalized hydroxamic acid derivatives using a cross-metathesis reaction between N