Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• all-syn stereochemistry [46]. This molecule adopts a helical conformation which maximises 1,2-difluoro gauche alignments and minimises 1,3-difluoro parallel alignments. (Note that the helix in this case is much “tighter” than the perfluoroalkane helix described above.) The helical conformation of 28

• leads to a low molecular dipole moment, because every C–F bond can be paired with another that has the opposite orientation. In contrast, compound 29 (Figure 4) divides the six fluorines into two groups of three, separated by an ethylene spacer [47]. The same helical conformation is maintained, but the

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• helical conformation was confirmed by the single-crystal X-ray crystallography of its methoxy-substituted analogue. Another method to obtain the incompletely cyclized seco-HBC is the introduction of a non-hexagonal ring into the precursors of HBC. Due to the large ring strain, the precursors are not prone

• . And the derivative 16 was also synthesized by allylic oxidation of compound 15 using selenium dioxide. As helical chiral NGs, helicene 14 and its derivatives 15 and 16 showed highly distorted helical conformation and also exhibited a relatively high isomerization barrier (over 28.9 kcal/mol determined

• , which formed intermediate 109 in a high yield. Finally, DDQ and TfOH induced the Scholl oxidation of 109 to generate 110 in a yield of 24%. Single-crystal X-ray diffraction unambiguously confirmed the helical conformation and a pair of enantiomers. Chiral resolution of enantiomers was achieved by chiral

First series of N-alkylamino peptoid homooligomers: solution phase synthesis and conformational investigation

• Maxime Pypec,
• Laurent Jouffret,
• Claude Taillefumier and
• Olivier Roy

Beilstein J. Org. Chem. 2022, 18, 845–854, doi:10.3762/bjoc.18.85

• extended right-handed helical conformation with backbone torsion angle (φ, ψ) values in vicinity of (100°, −173°), approximately 3 residues per turn, and a helical pitch of 10 Å (Figure 6C). The structure resembles the type II polyproline helix, with a slightly larger pitch. Conclusion This report

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• - instead of 7-bromotryptophan yielded the expected stapled peptide P1a. Next, the secondary structures of the two stapled peptides P1a and P1b were investigated by CD spectroscopy. Unfortunately, both peptides did not show enhanced helical conformation in water. To get more information about the structure

• higher probability of occurrence (17.8%). The non-helical conformation c3 of P5 trans (7.5%) is slightly less populated than the corresponding c2 of P5 cis. The macrocycle of both isomers is found to be rather flexible, forming well-separated conformational clusters in the three-dimensional space of PC1

• -helical conformation, with a smaller yet substantial propensity to participate in turns and bends. Overall, P5 trans is the most helical peptide, followed by aAxWt, and P5 cis, and P6 is significantly less helical than the others, in terms of individual amino acid’s contributions. P6 stands out with a

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

• enantioselectivity, but the catalyst itself accommodates the anion by adopting a helical conformation upon complexation (Scheme 18a) [84][85][86]. Initial studies proved these systems highly effective for the enantioselective Reissert reaction of quinolines with silyl ketene acetals [22], which could be later

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• ]. The replacement of a single Glc unit with a Man unit was sufficient to disrupt this secondary structure and significantly increased the isolated yield of the final compounds. Molecular dynamic (MD) simulations predicted a compact helical conformation for the fully deprotected compound, confirmed by

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

• PNA was able to adopt to the conformations of DNA and RNA to some extent, the P-form was the naturally preferred helical conformation of PNA. PNA backbone modifications PNA design was originally assisted by simple computer modeling that replaced the phosphodiester backbone of DNA with pseudopeptide

• dichroism studies showed that the ᴅ-Lys modification induced a right-handed helical conformation favorable for DNA binding while the ʟ-Lys modification induced a left‐handed helical conformation that disfavored PNA binding to DNA [69]. Interestingly, a crystal structure of PNA having three α-ᴅ-Lys

pH- and concentration-dependent supramolecular self-assembly of a naturally occurring octapeptide

• Goutam Ghosh and
• Gustavo Fernández

Beilstein J. Org. Chem. 2020, 16, 2017–2025, doi:10.3762/bjoc.16.168

• File 1) and the helical conformation (Figure S6, Supporting Information File 1) as well as a ThT assay for the β-sheet (Figure S7, Supporting Information File 1) to better understand a possible conformational transition over time. However, no changes in the particular conformation were found even after

Synthesis, liquid crystalline behaviour and structure–property relationships of 1,3-bis(5-substituted-1,3,4-oxadiazol-2-yl)benzenes

• Afef Mabrouki,
• Malek Fouzai,
• Armand Soldera,
• Abdelkader Kriaa and
• Ahmed Hedhli

Beilstein J. Org. Chem. 2020, 16, 149–158, doi:10.3762/bjoc.16.17

• crystalline state, the perfluorocarbon chain adopt a helical conformation of the carbon backbone [36]. The cylinder-like structure of the segment (CF2)m resembles a stiff rod in which the carbon skeleton is covered by fluorine atoms. In the hydrocarbon counterpart the segment (CH2)n adopts the typical in

Sugar-derived oxazolone pseudotetrapeptide as γ-turn inducer and anion-selective transporter

• Sachin S. Burade,
• Sushil V. Pawar,
• Tanmoy Saha,
• Navanath Kumbhar,
• Amol S. Kotmale,
• Manzoor Ahmad,
• Pinaki Talukdar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2019, 15, 2419–2427, doi:10.3762/bjoc.15.234

• , coupling reactions of 8/9 with different reagents (HATU, TBTU, PyBOP, EDC·HCl), under a variety of solvents (DMF, acetonitrile, dichloromethane) and reaction conditions (25–80 °C for 24 h) were unsuccessful. This could be due to the stable helical conformation of 8 and 9 in which reactive acid and amino

• optimization on TFSAA linear tetrapeptide amino acid 9 (Figure 5C). The optimized geometry of 9 showed a change in helical conformation overcome the crowding due to acetonide groups. The N- and C-terminals are further away, thus precluding the γ-turn conformation [(bond distance (d) = 3.11 Å) and bond angle

6’-Fluoro[4.3.0]bicyclo nucleic acid: synthesis, biophysical properties and molecular dynamics simulations

• Sibylle Frei,
• Andrei Istrate and
• Christian J. Leumann

Beilstein J. Org. Chem. 2018, 14, 3088–3097, doi:10.3762/bjoc.14.288

• attributed to the conformational restriction of the sugar [62][64]. The Gibbs free energy of duplex formation corresponded well with the observed Tm values. CD spectroscopy Circular dichroism of ON1–7 paired with DNA or RNA was recorded to further analyze their helical conformation and to compare it with

Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications

• Mattias Bood,
• Sangamesh Sarangamath,
• Moa S. Wranne,
• Morten Grøtli and
• L. Marcus Wilhelmsson

Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7

• conformations depending on conditions. Z-DNA, a GC-repeat rich, thermodynamically less preferred, left-handed helical conformation that is favored by cytosine methylation is known to form in vivo under negative supercoiling or high salt concentrations [64][65][66][67][68]. Circular dichroism is traditionally

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• designed and synthesized various chiral triazole-based complexes such as L2–L4 (Scheme 2) [36][37][38][39]. It was proposed that while these triazole derivatives are conformationally flexible, upon their binding to halogen anions these complexes adopt a reinforced chiral helical conformation. The resultant

Supramolecular chemistry: from aromatic foldamers to solution-phase supramolecular organic frameworks

• Zhan-Ting Li

Beilstein J. Org. Chem. 2015, 11, 2057–2071, doi:10.3762/bjoc.11.222

• naphthalene units in longer 12f–h stacked intramolecularly to induce the oligomeric chains to form a helical conformation at high acetonitrile content (Scheme 6). The compact helical conformation gave rise to a cavity similar to that of 18-crown-6 and thus could complex ammonium or ethane-1,2-diaminium in

• chloroform-d and crystal structure analysis of model molecules all supported that fluorine was engaged in the expected intramolecular F···H–N hydrogen bonding and 24 formed a helical conformation (Scheme 12). Moreover, Chuang found that intermolecular F···H–N hydrogen bonding could also be formed between 23

• compounds 12a–g and the formation of the helical conformation by the longer oligomers. The structures of compounds 13a,b, 14, and 15a–d. The structures of complex C60 16 and dynamic [2]catenane formed by compounds 17–19. The structure of homodimers 20a·20a and 20b·20b. The structures of foldamers 21 and

Exploring monovalent and multivalent peptides for the inhibition of FBP21-tWW

• Lisa Maria Henning,
• Sumati Bhatia,
• Miriam Bertazzon,
• Michaela Marczynke,
• Oliver Seitz,
• Rudolf Volkmer,
• Rainer Haag and
• Christian Freund

Beilstein J. Org. Chem. 2015, 11, 701–706, doi:10.3762/bjoc.11.80

• by the individual WW domains [5]. At position P4 proline can be replaced by leucine, a residue well compatible with the PPII helical conformation. Arginine is preferred at position 6 or 9, highlighting the importance of a positive charge in complex formation. Interestingly, WW1 tolerates an exchange

Molecular architecture with carbohydrate functionalized β-peptides adopting 3₁₄-helical conformation

• Nitin J. Pawar,
• Navdeep S. Sidhu,
• George M. Sheldrick,
• Dilip D. Dhavale and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2014, 10, 948–955, doi:10.3762/bjoc.10.93

The influence of intraannular templates on the liquid crystallinity of shape-persistent macrocycles

• Joscha Vollmeyer,
• Ute Baumeister and
• Sigurd Höger

Beilstein J. Org. Chem. 2014, 10, 910–920, doi:10.3762/bjoc.10.89

• 1c, the length of the template seems to be similar to the alkyl template in 1a. However, the tendency of oligoethylene oxides to obtain a helical conformation [55] may fold the arylene–acetylene backbone into a boat conformation which is no longer a discotic mesogen. For the macrocycles 2a–d, the

Conformation of dehydropentapeptides containing four achiral amino acid residues – controlling the role of L-valine

• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Maciej Makowski,
• Rafał Latajka and
• Paweł Kafarski

Beilstein J. Org. Chem. 2014, 10, 660–666, doi:10.3762/bjoc.10.58

• right-handed helical conformation. Keywords: conformation; dehydroalanine; dehydropeptide; dehydrophenylalanine; NMR; Introduction Structurally modified peptides are becoming increasingly interesting as potential substances with pharmacological effects [1]. Dehydropeptides are one representative of

• even in the case of short peptides [8][9][10]. This influence is stronger for peptides with a longer main chain, for which a 310-helical conformation could be observed [8][11][12][13]. Peptides containing a dehydroalanine residue usually have an inverse γ-turn conformation [7][14][15]. Another

• well-defined conformation. As shown in Figure 4 peptide 3 has a helical conformation. Both α- and 310-helix give a similar vicinity of the backbone protons of nonconsecutive residues between Hαi–HNi+2 and Hαi–HNi+3 [35]. Inai and Hirabayashi showed that the presence of NOE signals between Hαi–HNi+4

Bis(benzylamine) monomers: One-pot preparation and application in dendrimer scaffolds for removing pyrene from aqueous environments

• Olivia N. Monaco,
• Sarah C. Tomas,
• Meghan K. Kirrane and
• Amy M. Balija

Beilstein J. Org. Chem. 2013, 9, 2320–2327, doi:10.3762/bjoc.9.266

• . The triphenol cores were utilized to examine how the core diameter and shape influenced the chemical and physical properties of the resulting dendrimers. Cores 5 and 9 were calculated to exist in a helical conformation with an average diameter of 5.7 Å while 10 was present as a planar structure with

Design of a novel tryptophan-rich membrane-active antimicrobial peptide from the membrane-proximal region of the HIV glycoprotein, gp41

• Evan F. Haney,
• Leonard T. Nguyen,
• David J. Schibli and
• Hans J. Vogel

Beilstein J. Org. Chem. 2012, 8, 1172–1184, doi:10.3762/bjoc.8.130

• and Leu residues are removed from the hydrophilic surface and are replaced with cationic residues. This generates a peptide with a large net positive charge (+9) and if it can still adopt a helical conformation, then it will be highly amphipathic. The final gp41w derivative, gp41w-FKA, has the same

• and a maximum peak at ~195 nm, suggesting that this peptide already adopts a partially helical conformation in aqueous buffer. The CD spectra of gp41w are even more intriguing as there are strong minima observed at 230 and 208 nm. The peak at 208 nm is likely due to the presence of α-helical structure

• -helix. When compared to the curve of gp41w-4R in 50% TFE, the traces from the micelle-containing samples show little difference, indicating that the conformation of gp41w-4R is similar in all these environments. In the presence of 50% TFE, gp41w also adopts a largely α-helical conformation, but in the

Partial thioamide scan on the lipopeptaibiotic trichogin GA IV. Effects on folding and bioactivity

• Marta De Zotti,
• Barbara Biondi,
• Cristina Peggion,
• Matteo De Poli,
• Haleh Fathi,
• Simona Oancea,
• Claudio Toniolo and
• Fernando Formaggio

Beilstein J. Org. Chem. 2012, 8, 1161–1171, doi:10.3762/bjoc.8.129

• single thioamide replacement was incorporated. Sequence positions near the N-terminus, at the center, and near the C-terminus were investigated. Our results indicate that (i) a thioamide linkage is well tolerated in the overall helical conformation of the [Leu11-OMe] lipopeptide analogue and (ii) this

• in Figure S-I, Supporting Information File 1. All these structures converge to a well-defined, right-handed, mixed 310-/α-helical conformation throughout the sequence with a backbone average pairwise root-mean-square deviation of 0.49 ± 0.18 Å (deviations from idealized geometry and mean energies for

• ± 2.9°) was detected at the C-terminus. In conclusion, the MD calculations based on the restraints derived from the ROESY spectrum of ψ[CS-NH]9 reveal the marked preference of this analogue for a mixed α-/310- helical conformation, with a clear α-helical character at the C-terminus on which the

Control over molecular motion using the cis–trans photoisomerization of the azo group

• Estíbaliz Merino and
• María Ribagorda

Beilstein J. Org. Chem. 2012, 8, 1071–1090, doi:10.3762/bjoc.8.119

• described by Woolley et al. [92][93]. They introduced an azobenzene moiety in a polypeptide to control the α-helical conformation and to have a synthetic tool that allows photomodulation of the very important conformation–interaction relationship in biological recognition. Peptides with pairs of cysteine

• and its α-helical conformation. The photoisomerization leads to the cis isomer, which disrupts this helicity inhibiting the association with DNA. The photoreversion to the trans isomer recovers again the final conformation of the α-helix of DNA. In 2011, the same group carried out the attachment of a

Intramolecular bridges formed by photoswitchable click amino acids

• Christian Hoppmann,
• Ronald Kühne and
• Michael Beyermann

Beilstein J. Org. Chem. 2012, 8, 884–889, doi:10.3762/bjoc.8.100

• presence of glutathione as an additional thiol the click reaction of the PSCaa occurs intramolecularly with the cysteine rather than with the glutathione, indicating that the click reaction may be used even under reducing conditions occurring in living cells. Keywords: azobenzene; helical conformation

• spacing (5.4 Å). Moreover, the different distances covered by the cis and the trans form of the photocontrollable bridge explain the significant stabilization of the α-helical conformation of the crosslinked peptide 3 (Scheme 2) with i,i+4 spacing in the cis form in contrast to the more extended trans

• form, which disturbs an α-helical conformation [6]. To study the effect of i,i+4 or i,i+7 spacings on the efficiency of intramolecular thiol–ene click reactions of the PSCaa with a cysteine in an α-helical structure, we compared the reaction in peptide 1 with i,i+4 and peptide 2 with i,i+7 spacing in

Supramolecular FRET photocyclodimerization of anthracenecarboxylate with naphthalene-capped γ-cyclodextrin

• Qian Wang,
• Cheng Yang,
• Gaku Fukuhara,
• Tadashi Mori,
• Yu Liu and
• Yoshihisa Inoue

Beilstein J. Org. Chem. 2011, 7, 290–297, doi:10.3762/bjoc.7.38

• -dependent. The addition of AC (0–0.26 mM) to the above solutions of 7 or 6 (0.2 mM) produced a strong positive exciton couplet at the 1Bb transition of AC (Figure 2 and Figure 3) which overwhelmed the inherent signals. The positive couplet observed indicates the right-handed helical conformation of the two

The C–F bond as a conformational tool in organic and biological chemistry

• Luke Hunter

Beilstein J. Org. Chem. 2010, 6, No. 38, doi:10.3762/bjoc.6.38

• . This concept is elegantly illustrated by the diastereoisomeric β-peptides 66 and 67 (Figure 18) [56]. The β-amino acid sequence of 66 and 67 is known to promote the formation of a left-handed helix and this helical conformation can be either reinforced or destabilised by a fluorine substituent. In the

• case of β-peptide 66, the fluorine atom aligns antiparallel to the adjacent C=O bond and gauche to the adjacent amide nitrogen, and this reinforces the helical conformation of the β-peptide. In contrast, the helical conformation of β-peptide 67 cannot accommodate these favourable alignments, so in this

• 65. The electron-withdrawing trifluoromethyl group of 65 disrupts a key hydrogen bond, leading to a different conformation as determined by NOESY experiments. The C–F bond influences the conformation of β-peptides. β-Heptapeptide 66 adopts a helical conformation, reinforced by the α-fluoroamide