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

• different amides, including dipeptides, under mild and operationally simple conditions in high yields. Mechanistic studies suggest that BT-SCF3 can generate acyl fluorides from carboxylic acids via two distinct pathways, which allows the deoxyfluorinating reagent to be employed in sub-stoichiometric amounts

Phenanthridine–pyrene conjugates as fluorescent probes for DNA/RNA and an inactive mutant of dipeptidyl peptidase enzyme

• Josipa Matić,
• Tana Tandarić,
• Marijana Radić Stojković,
• Filip Šupljika,
• Zrinka Karačić,
• Ana Tomašić Paić,
• Lucija Horvat,
• Robert Vianello and
• Lidija-Marija Tumir

Beilstein J. Org. Chem. 2023, 19, 550–565, doi:10.3762/bjoc.19.40

• ) inactive enzyme mutant E451A was examined by fluorimetric titrations and ITC titrations and it was found that Phen-Py-1 binds to the protein with a high affinity (Table 3). This protein is a mono-zinc metalloexopeptidase and hydrolyses dipeptides from the N-termini of substrates that consist of at least

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• chirality transfer. With this positive results in hand, we incorporated 5 into the desired tetrapeptide 8. So far, we carried out peptide Claisen rearrangements only with small dipeptides, but never used longer peptide chains, such as tetrapeptides. We knew from previous work that the protecting groups on

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• product (98% yield) (Scheme 20C). More complex structures like dipeptides and substrates containing multiple Lewis-basic functionalities also presented good yields and chemoselectivities with this protocol. The robust allylation reaction was tested in even more complex structures, including steroid

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• synthesis of unnatural α-amino acids 129 and precise alkylation modification of peptides in the later stage (Scheme 45). Even in the presence of other amino acid residues, this protocol has excellent regio- and chemoselectivity, providing a sequence of novel corresponding dipeptides with good yield. The

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• give rise to the phosphonodepsidipeptide 61. The phosphonodepsidipeptide 61 was also obtained directly by the oxidation of the phosphinate 59 with carbon tetrachloride in the presence of the hydroxy ester 60. After hydrogenolysis of 61 and coupling with various N-protected dipeptides 62, the N

Automated high-content imaging for cellular uptake, from the Schmuck cation to the latest cyclic oligochalcogenides

• Rémi Martinent,
• Javier López-Andarias,
• Dimitri Moreau,
• Yangyang Cheng,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2020, 16, 2007–2016, doi:10.3762/bjoc.16.167

• . Schematic representation of binding models between organic cations (simple ammonium, guanidinium, Schmuck cation) and oxoanions. From Schmuck cations to cell-penetrating dipeptides, with schematic representation of the binding model between GCPs and GAGs on the cell surface, and with DNA. Peptide tweezers

A dynamic combinatorial library for biomimetic recognition of dipeptides in water

• Florian Klepel and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2020, 16, 1588–1595, doi:10.3762/bjoc.16.131

• developed a DCL composed of Cu2+, Ni2+ complexes. The addition of dipeptides caused characteristic spectral changes by ligand-exchange reactions [18]. We previously used a peptide derived DCL for the development of artificial carbohydrate receptors [19][20]. An intriguing example derived from that work is

• slightly alkaline buffer (pH 7.4). An excess of our target molecules, the simple dipeptides AA, FF and YY (Y for tyrosine), were added to one sample each. An additional sample without dipeptide addition served as reference. After several hours of stirring in an open vial the thiol functions of the

• dimers in comparison to the reference (Figure 2a, full chromatograms Figures S2–S4, Supporting Information File 1). Amplification of both peak areas is observed for all templates, which indicates an interaction between the dipeptides and the cyclic tripeptide dimers. For the second peak the change is

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• fluorinated Phe dipeptides [84] 177c–g as racemic mixtures (Scheme 43). 5. Pharmaceutical applications of fluorinated phenylalanine derivatives Peptides and proteins containing FPhe are important tools to identify enzyme–substrate complexes, mechanisms of protein aggregation, and modifying the chemical and

Synthesis of new asparagine-based glycopeptides for future scanning tunneling microscopy investigations

• Laura Sršan and
• Thomas Ziegler

Beilstein J. Org. Chem. 2020, 16, 888–894, doi:10.3762/bjoc.16.80

• significantly higher yield than HBTU. The Fmoc cleavage of the compounds 3–5 was performed with piperidine in DMF (20 vol %) [36]. The reaction products were not isolated and purified but instead immediately used for the succeeding peptide coupling step to give the dipeptides 4 and 5 from the glycosylated

Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides

• Rosana Ribić,
• Ranko Stojković,
• Lidija Milković,
• Mariastefania Antica,
• Marko Cigler and
• Srđanka Tomić

Beilstein J. Org. Chem. 2019, 15, 1805–1814, doi:10.3762/bjoc.15.174

• present the design, synthesis and biological evaluation of novel mannosylated desmuramyl peptide derivatives. Mannose was coupled to dipeptides containing a lipophilic adamantane on N- or C-terminus through a glycolyl or hydroxyisobutyryl linker. Adjuvant activities of synthesized compounds were

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• inhibitors. When the aziridine-aldehyde (2R,1'R)-6 was subjected to the reductive amination with 4 dipeptides secondary amines 172 (a R' = iBu, R''= sec-Bu; b R' = R'' = iBu; c R' = sec-Bu, R'' = iBu; d R' = R'' = sec-Bu) were produced (Scheme 44) [101]. In the presence of triphosgene a series of imidazolin

• -2-ones having a 2-chloromethyl substituent 173 was formed. Removal of the 1-phenylethyl moiety and a subsequent replacement of the chlorine atom by the amino group via azide gave imidazolin-2-one dipeptides 174 which were transformed into 12 derivatives 175–177 after hydrolysis of the corresponding

Synthesis of C₃-symmetric star-shaped molecules containing α-amino acids and dipeptides via Negishi coupling as a key step

• Sambasivarao Kotha and
• Saidulu Todeti

Beilstein J. Org. Chem. 2019, 15, 371–377, doi:10.3762/bjoc.15.33

• ) derivatives and dipeptides. In this regard, trimerization and Negishi cross-coupling reactions are used as the key steps starting from readily available 4’-iodoacetophenone and L-serine. These C3-symmetric molecules containing AAA moieties are useful to design new ligands suitable for asymmetric synthesis and

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• the N-Boc protected β-hydroxy sulfide 130 as a key intermediate. Deprotection of the Boc followed by the imidation of the free amine with protected dipeptides that mimic Leu-Val produced the inhibitors of human renin 131 as depicted in Scheme 44. Yoshioka and co-workers reported two synthetic routes

Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis

• Dan Liu,
• Ya-Li Guo,
• Jin Qu and
• Chi Zhang

Beilstein J. Org. Chem. 2018, 14, 1112–1119, doi:10.3762/bjoc.14.97

• obtain various dipeptides from standard amino acids as well as sterically hindered amino acids. Moreover, a pentapeptide Leu-enkephalin is successfully synthesized in its protected form using this coupling system. Similar to iodosodilactone, FPID can be easily regenerated after the reaction. The

A mechanochemical approach to access the proline–proline diketopiperazine framework

• Nicolas Pétry,
• Hafid Benakki,
• Eric Clot,
• Pascal Retailleau,
• Farhate Guenoun,
• Fatima Asserar,
• Chakib Sekkat,
• Thomas-Xavier Métro,
• Jean Martinez and
• Frédéric Lamaty

Beilstein J. Org. Chem. 2017, 13, 2169–2178, doi:10.3762/bjoc.13.217

• . Subsequently, the mechanocoupling of hindered proline amino acid derivatives was developed to provide proline–proline dipeptides under solvent-free conditions. A deprotection–cyclization sequence yielded the corresponding diketopiperazines that were obtained with a high stereoselectivity which could be

• heterocyclic structures, usually derived from dipeptides, which find many applications in chemistry and biology, and have attracted attention in the last years [1][2]. The diketopiperazine backbone can be found in many natural products exhibiting various biological activities [3]. Consequently, medicinal

• aminolysis. This strategy has been extensively used [1], involving milder conditions and provides access to unsymmetrical dipeptides and DKPs. Furthermore, substituted prolines could be obtained by nucleophilic substitution of benzylamine from dimethyl dibromoadipate, allowing the addition of functional

Peptide synthesis: ball-milling, in solution, or on solid support, what is the best strategy?

• Ophélie Maurin,
• Pascal Verdié,
• Gilles Subra,
• Frédéric Lamaty,
• Jean Martinez and
• Thomas-Xavier Métro

Beilstein J. Org. Chem. 2017, 13, 2087–2093, doi:10.3762/bjoc.13.206

• without solvent (BM strategy). On the other hand, the dipeptides were obtained with higher purity when synthesized using the conventional solution strategy compared to the BM approach (Table 1, entries 1 and 2). Yet, for all tripeptides and tetrapeptides, the BM strategy furnished the products with higher

• . Conclusion Overall, both in terms of yield and purity, the efficiency of the three strategies can be ranked as follows: BM ≈ SPPS > solution. Of note, the solution strategy gave the dipeptides with higher purity than the ball-milling approach. Although SPPS is the strategy of choice towards long peptides so

Chemical systems, chemical contiguity and the emergence of life

• Terrence P. Kee and
• Pierre-Alain Monnard

Beilstein J. Org. Chem. 2017, 13, 1551–1563, doi:10.3762/bjoc.13.155

• , which are potential functional catalysts, can also be synthesized from simple amino acids [40]. Indeed, dipeptides can catalyse RNA oligomer formation in the eutectic phase of water/ice [41], underscoring another possible chemical contiguity within the geochemical context. The ubiquity of polyphosphate

Versatile synthesis of the signaling peptide glorin

• Robert Barnett,
• Daniel Raszkowski,
• Thomas Winckler and
• Pierre Stallforth

Beilstein J. Org. Chem. 2017, 13, 247–250, doi:10.3762/bjoc.13.27

• furnished the protected dipeptides 8a and 8b, respectively. Hydrogenolysis with hydrogen gas and palladium on charcoal gave free amines 9a and 9b. Glorin (1) and glorinamide 2 were then obtained by treating amines 9a and 9b, respectively, with propionic anhydride. The main advantage of our synthesis over

Gold-catalyzed direct alkynylation of tryptophan in peptides using TIPS-EBX

• Gergely L. Tolnai,
• Jonathan P. Brand and
• Jerome Waser

Beilstein J. Org. Chem. 2016, 12, 745–749, doi:10.3762/bjoc.12.74

• other aromatic amino acids, such as phenylalanine or tyrosine (products 5c and 5d). Serine and proline containing dipeptides 5e and 5f could also be obtained in 64% and 53% yield, respectively. The reaction was therefore general for dipeptides bearing tryptophan at the C-terminus. On the other hand

Studies on the synthesis of peptides containing dehydrovaline and dehydroisoleucine based on copper-mediated enamide formation

• Franziska Gille and
• Andreas Kirschning

Beilstein J. Org. Chem. 2016, 12, 564–570, doi:10.3762/bjoc.12.55

• conditions (Table 1, entry 8). Next, we tested these reaction conditions for the preparation of the other dehydrovaline bearing peptide fragment of myxovalargin 1 (amino acids 7–9). First, dipeptides 18–21 and methyl esters 22 and 23 were N-acylated with vinyl iodide 10 to yield peptidic vinyl iodides 24–29

My maize and blue brick road to physical organic chemistry in materials

• Anne J. McNeil

Beilstein J. Org. Chem. 2016, 12, 229–238, doi:10.3762/bjoc.12.24

• most widely investigated class of molecular gelators and their gelation ability is highly dependent on their sequence (e.g., 3a versus 3b, Figure 3) [34]. We again observed the trend that gelators exhibit higher dissolution enthalpies. During these studies, we discovered that several dipeptides

Star-shaped tetrathiafulvalene oligomers towards the construction of conducting supramolecular assembly

• Masahiko Iyoda and
• Masashi Hasegawa

Beilstein J. Org. Chem. 2015, 11, 1596–1613, doi:10.3762/bjoc.11.175

• derived from the self-assembly of TTF-appended dipeptides were reported [77]. Conductivity measurements performed on the nanofibers of TTF-appended dipeptides indicate a remarkable enhancement in the conductivity after doping with TCNQ (σrt = 1 × 10−5 S cm−1). Conducting nanostructures prepared from

Synthesis of aromatic glycoconjugates. Building blocks for the construction of combinatorial glycopeptide libraries

• Markus Nörrlinger and
• Thomas Ziegler

Beilstein J. Org. Chem. 2014, 10, 2453–2460, doi:10.3762/bjoc.10.256

• -containing derivatives 1a and 2a for an exemplified preparation of the corresponding fully protected dimers. For comparison reasons and the possibility to later construct glycopeptides containing non-glycosylated chain links, we also prepared two dipeptides from nitro-benzoates 6 and 8 in the following way

• gave non-glycosylated fully protected dipeptides 17 and 20 in 73% and 88% yield, respectively (Scheme 2). Likewise, the Fmoc protecting groups in glucosylated building blocks 13a and 14a were first removed with piperidine in DMF to give crude aminomethyl derivates 21 and 23. Next, the latter were

• coupled with 1a (for 21) and 2a (for 23) under similar conditions as described for the non-glycosylated counterparts above to afford glycol-dipeptides 22 and 24 in 51% and 55% yield, respectively. As was observed for EDCI-promoted preparation of glycosylated derivatives 13 and 14 (see Table 2), the yields

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• reported [147]. A wide variety of aldehydes, primary amines and carboxylic acids were tolerated resulting in a library of 80 different linear dipeptides. Cleavage from the carbonate resin with KOt-Bu afforded compound 176 which was converted to the methyl ester 177 using NaOMe (Scheme 54). Subsequent TFA