Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• et al. [47]. These syntheses substituted the enduracididine residue for the more readily available L-arginine. The total synthesis of the full teixobactin structure was completed in 2016 by Payne et al. [72] using Fmoc solid-phase peptide synthesis (SPPS). The key to the synthesis was access to the

• synthetic routes to enduracididine. However, current syntheses are cumbersome and inefficient. A robust and scalable synthetic route to an orthogonally protected enduracididine derivative suitable for solid phase peptide synthesis would greatly facilitate antibiotic drug development focused on a teixobactin

Assembly of synthetic Aβ miniamyloids on polyol templates

• Sebastian Nils Fischer and
• Armin Geyer

Beilstein J. Org. Chem. 2015, 11, 2646–2653, doi:10.3762/bjoc.11.284

• , Aβ peptide pentapeptide boronic acids 1 and 2 were synthesized by solid-phase peptide synthesis and studied in esterification experiments with polyhydroxylated templates. The bis-hydroxylated dipeptide Hot=Tap serves as a template of adjustable degree of oligomerization which spontaneously forms

• obtained by routine solid-phase peptide synthesis on chloro-(2'-chloro)trityl polystyrene (CTC resin) and coupling of the unprotected boronic acid as the final building block. The C-terminal boronic acids need careful exclusion of water because of the reversible linkage to the resin, while no special

Synthesis and evaluation of the biostability and cell compatibility of novel conjugates of nucleobase, peptidic epitope, and saccharide

• Dan Yuan,
• Xuewen Du,
• Junfeng Shi,
• Ning Zhou,
• Abdulgader Ahmed Baoum,
• Khalid Omar Al Footy,
• Khadija Omar Badahdah and
• Bing Xu

Beilstein J. Org. Chem. 2015, 11, 1352–1359, doi:10.3762/bjoc.11.145

• .11.145 Abstract This article reports the synthesis of a new class of conjugates containing a nucleobase, a peptidic epitope, and a saccharide and the evalution of their gelation, biostability, and cell compatibility. We demonstrate a facile synthetic process, based on solid-phase peptide synthesis of

• designed the nucleopeptides 5 and 6. In addition, we substituted thymine with adenine to generate nucleopeptides 7 and 8 that contain adenine, the nucleobase is complementary of thymine. Synthesis The NA conjugates 5–8 were obtained according to a facile method of solid-phase peptide synthesis (SPPS) [17

• solid-phase peptide synthesis and liquid-phase synthesis). i) Fmoc-Val-OH, DIPEA; ii) 20% piperidine; iii) Fmoc-Pro-OH, HBTU, DIPEA; iv) Fmoc-Thr(t-Bu)-OH, HBTU, DIPEA; v) thymine-1-acetic acid, HBTU, DIPEA; vi) TFE/DCM 2:8; vii) D-glucosamine hydrochloride, HBTU, DIPEA; viii) TFA/H2O 95:5

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• structural explanation of observed ICD recognition. Laborious synthetic procedures for the preparation of bis-phenanthridine–nucleobase conjugates initiated a novel, convergent and much more flexible approach relying on solid phase peptide synthesis described earlier (Figure 4). In such a manner prepared

Versatile synthesis of amino acid functionalized nucleosides via a domino carboxamidation reaction

• Vicky Gheerardijn,
• Jos Van den Begin and
• Annemieke Madder

Beilstein J. Org. Chem. 2014, 10, 2566–2572, doi:10.3762/bjoc.10.268

• functionalized amino acids onto nucleoside building blocks (Figure 1). Following the event of solid phase peptide synthesis, a large range of amino acids with different protection schemes and stereochemistry is currently commercially available. We here illustrate a methodology for direct incorporation of amino

Towards the sequence-specific multivalent molecular recognition of cyclodextrin oligomers

• Michael Kurlemann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 2428–2440, doi:10.3762/bjoc.10.253

• Supporting Information File 1). The di- and trivalent guest strands 8–14 (Figure 1C, D) were synthesized by solid phase peptide synthesis using a standard Fmoc-protocol (Figure 3). Therefore the serine derivatives 15 and 16 (Figure 1E) and a water-soluble linker molecule were used. The purity of the guest

• ). Synthesis of the di- and trivalent CD sequences 1–7 (for detailed reaction conditions see Supporting Information File 1). Solid phase peptide synthesis of the di- and trivalent guest strands 8 – 14 (for detailed reaction conditions see Supporting Information File 1). 1H NMR spectra of 17 (B) and its

Synthesis of novel conjugates of a saccharide, amino acids, nucleobase and the evaluation of their cell compatibility

• Dan Yuan,
• Xuewen Du,
• Junfeng Shi,
• Ning Zhou,
• Abdulgader Ahmed Baoum and
• Bing Xu

Beilstein J. Org. Chem. 2014, 10, 2406–2413, doi:10.3762/bjoc.10.250

• synthesis of a novel type of conjugate of three fundamental biological build blocks (i.e., saccharide, amino acids, and nucleobase) and their cell compatibility. The facile synthesis starts with the synthesis of nucleobase and saccharide derivatives, then uses solid-phase peptide synthesis (SPPS) to build

• . Synthesis Schemes 1–4 show the syntheses of the SAN conjugates formed by the reaction of the amino acid segment with the nucleobase and the saccharide derivative. The key steps include N-alkylation, acetylation, solid-phase peptide synthesis (SPPS) and N-hydroxysuccinimide (NHS)/N,N-diisopropylcarbodiimide

• 12, 16, and 19. Solid-phase peptide synthesis of peptide segment Fmoc-naphthAla-Phe-Arg(pbf)-Gly-Asn(Ot-Bu)-OH (20). Synthesis of H-naphthAla-Phe-Arg(pbf)-Gly-Asn(Ot-Bu)-adenine (22). Synthesis of saccharide–amino acids–nucleobase conjugate 3. Supporting Information Supporting Information File 432

Convergent synthetic methodology for the construction of self-adjuvanting lipopeptide vaccines using a novel carbohydrate scaffold

• Vincent Fagan,
• Istvan Toth and
• Pavla Simerska

Beilstein J. Org. Chem. 2014, 10, 1741–1748, doi:10.3762/bjoc.10.181

• previously reported carbohydrate-based vaccine constructs [11] were prepared by a divergent approach, where the carbohydrate core was coupled to the resin-bound LCP adjuvanting moiety, followed by stepwise synthesis of the B cell epitopes using solid-phase peptide synthesis (SPPS). Using this divergent

Orthogonal dual thiol–chloroacetyl and thiol–ene couplings for the sequential one-pot assembly of heteroglycoclusters

• Michele Fiore,
• Gour Chand Daskhan,
• Baptiste Thomas and
• Olivier Renaudet

Beilstein J. Org. Chem. 2014, 10, 1557–1563, doi:10.3762/bjoc.10.160

• 3000+ Bruker Daltonics in positive mode. General procedure for solid-phase peptide synthesis. Assembly of all protected peptides was carried out on a synthesizer (Syro II, Biotage) using the Fmoc/t-Bu strategy and the Fmoc-Gly-SasrinTM resin. Coupling reactions were performed using, relative to the

Design, automated synthesis and immunological evaluation of NOD2-ligand–antigen conjugates

• Marian M. J. H. P. Willems,
• Gijs G. Zom,
• Nico Meeuwenoord,
• Ferry A. Ossendorp,
• Herman S. Overkleeft,
• Gijsbert A. van der Marel,
• Jeroen D. C. Codée and
• Dmitri V. Filippov

Beilstein J. Org. Chem. 2014, 10, 1445–1453, doi:10.3762/bjoc.10.148

• . We here describe the assembly of MDP building blocks, suitable for automated solid phase peptide synthesis (SPPS), their use in the assembly of the four MDP-antigen conjugates 2–5 and the immunological evaluation of the constructs. Results and Discussion Synthesis of the conjugates The MDP-antigen

• conjugates 2–5 were prepared using an automated solid-phase peptide synthesis (SPPS) protocol. In all these syntheses commercially available Tentagel S RAM resin and amino acids were applied. The synthesis of the required MDP building blocks 10 and 16 is depicted in Scheme 1. The 3-azidopropanol spacer was

• % yield. With MurNAc building block 10 and 16 in hand, the solid-phase peptide synthesis of the MDP-antigen conjugates 2–5 was undertaken (Scheme 2). Commercially available Fmoc protected amino acids equipped with standard acid labile protective groups were used. The side chain of the C-terminal lysine of

Molecular recognition of surface-immobilized carbohydrates by a synthetic lectin

• Melanie Rauschenberg,
• Eva-Corrina Fritz,
• Christian Schulz,
• Tobias Kaufmann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 1354–1364, doi:10.3762/bjoc.10.138

• lectins on the immobilized carbohydrates provides insight into the affinity and selectivity of lectin–carbohydrate interaction. Results and Discussion The synthetic lectin HisHis was prepared by air oxidation of the tripeptide Cys-Hys-Cys (synthesized by solid phase peptide synthesis) as described

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• their respective targets have led to tremendous progress for therapeutic applications in the last years. In order to increase the drugability of these frequently unstable and rapidly cleared molecules, chemical modifications are of great interest. Automated solid-phase peptide synthesis (SPPS) offers a

• : automated synthesis; automation; lipidation; PEGylation; peptide drugs; solid-phase peptide synthesis; therapeutic peptides; Introduction Peptides and proteins are involved in a large variety of biochemical processes and physiological functions. Peptides can consist of up to 50 amino acids and have

• intravenous) application, have prompted further research in this field [14]. Therefore, methods to prolong peptide stability are of great interest. Here, we highlight the importance of automated solid-phase peptide synthesis (SPPS) in the process of peptide modification. Principles of chemical synthesis of

Amino acid motifs in natural products: synthesis of O-acylated derivatives of (2S,3S)-3-hydroxyleucine

• Oliver Ries,
• Martin Büschleb,
• Markus Granitzka,
• Dietmar Stalke and
• Christian Ducho

Beilstein J. Org. Chem. 2014, 10, 1135–1142, doi:10.3762/bjoc.10.113

• derivatization as well as for solid-phase peptide synthesis. With respect to according motifs occurring in natural products, we have converted these building blocks into 3-O-acylated structures. Utilizing an esterification and cross-metathesis protocol, (2S,3S)-3-hydroxyleucine derivatives were synthesized, thus

• -Fmoc-protected building blocks potentially suitable for solid-phase peptide synthesis (SPPS). It is well established that O-acylated β-hydroxy-α-amino acids can be used in Fmoc-strategy peptide syntheses without migration of the acyl unit [37][38][39]. Based on these findings, we have desired to

• -phase peptide synthesis (SPPS). Furthermore, we have employed such building blocks for the synthesis of protected analogues 15a,b of the tripeptide unit of naturally occurring muraymycin nucleoside antibiotics. We have also established unprecedented protocols for early- and late-stage derivatizations of

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

• for carbohydrate and peptide chemistry. Therefore, sugar units are introduced by side-chain ligation and labeling strategies on the peptide scaffold or were established by incorporation of sugar-β-amino acids by solid-phase peptide synthesis (SPPS) [36][37]. Sugar amino acid building blocks have

Synthesis of enantiomerically pure (2S,3S)-5,5,5-trifluoroisoleucine and (2R,3S)-5,5,5-trifluoro-allo-isoleucine

• Holger Erdbrink,
• Elisabeth K. Nyakatura,
• Susanne Huhmann,
• Ulla I. M. Gerling,
• Dieter Lentz,
• Beate Koksch and
• Constantin Czekelius

Beilstein J. Org. Chem. 2013, 9, 2009–2014, doi:10.3762/bjoc.9.236

• synthesis of (2S,3S)-5,5,5-trifluoroisoleucine (L-5-F3Ile) and (2R,3S)-5,5,5-trifluoro-allo-isoleucine (D-5-F3-allo-Ile) was developed. The hydrophobicity of L-5-F3Ile was examined and it was incorporated into a model peptide via solid phase peptide synthesis to determine its α-helix propensity. The α-helix

• [14][15]. Therefore, the preparation of enantiomerically pure fluorinated isoleucine analogues with retained α-helix propensity is of general interest for site-specific modification of coiled-coil positions in parallel packing arrangements, especially when solid phase peptide synthesis is employed

One-step synthesis of pyridines and dihydropyridines in a continuous flow microwave reactor

• Mark C. Bagley,
• Vincenzo Fusillo,
• Robert L. Jenkins,
• M. Caterina Lubinu and
• Christopher Mason

Beilstein J. Org. Chem. 2013, 9, 1957–1968, doi:10.3762/bjoc.9.232

• chemistry [1], colloidal science [2], natural product chemistry [3], medicinal chemistry [4][5][6], solid-phase peptide synthesis [7] and in the biosciences [8]. Despite the many advantages of this heating method, and the introduction of a wide range of instrumentation [1], the scale up of microwave

Glycosylation efficiencies on different solid supports using a hydrogenolysis-labile linker

• Mayeul Collot,
• Steffen Eller,
• Markus Weishaupt and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 97–105, doi:10.3762/bjoc.9.13

• introduced the concept of solid-phase peptide synthesis in 1963 [1], synthesis on solid supports has evolved as a powerful tool for organic chemists [2]. Over the past fifty years this strategy has been successfully applied to the synthesis of other biopolymers, such as oligonucleotides [3] and

S-Fluorenylmethyl protection of the cysteine side chain upon N^α-Fmoc deprotection

• Johannes W. Wehner and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2012, 8, 2149–2155, doi:10.3762/bjoc.8.242

• ]. This is an attractive concept, because it can be combined with solid-phase peptide synthesis (SPPS) [4][5], as well as with native chemical ligation (NCL) utilizing an S→N acyl shift [3][6][7][8][9][10]. In addition, glycocysteine derivatives can be easily converted into the corresponding dimers by

Dimerization of a cell-penetrating peptide leads to enhanced cellular uptake and drug delivery

• Jan Hoyer,
• Ulrich Schatzschneider,
• Michaela Schulz-Siegmund and
• Ines Neundorf

Beilstein J. Org. Chem. 2012, 8, 1788–1797, doi:10.3762/bjoc.8.204

• . Peptide synthesis The peptides used were synthesized as described previously [30] by automated solid-phase peptide synthesis (SPPS) on a multiple Syro II peptide synthesizer (MultiSynTech, Witten, Germany) following Fmoc/t-Bu-strategy utilizing a double-coupling procedure and in situ activation with Oxyma

• -2,6-dioxocyclohex-1-ylidene)ethyl; SPPS: solid-phase peptide synthesis; TFA: trifluoroacetic acid; TIS: triisopropylsilane; HATU: O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate; DIPEA: diisopropylethylamine; TA: thioanisole; TC: p-thiocresol. Peptide sequences.a Analytical

Antifreeze glycopeptide diastereomers

• Lilly Nagel,
• Carsten Budke,
• Axel Dreyer,
• Thomas Koop and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 1657–1667, doi:10.3762/bjoc.8.190

• , peptides containing monosaccharide-substituted allo-L- and D-threonine building blocks were assembled by solid-phase peptide synthesis (SPPS). The retro-inverso AFGP analogue contained all amino acids in D-configuration, while the allo-L-diastereomer was composed of L-amino acids, like native AFGPs, with

Synthesis of trifunctional cyclo-β-tripeptide templates

• Frank Stein,
• Tahir Mehmood,
• Tilman Plass,
• Javid H. Zaidi and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2012, 8, 1576–1583, doi:10.3762/bjoc.8.180

• functionalization by amide bond formation. To protect the lysine side chain for selective and orthogonal amide-bond formation following the solid-phase peptide synthesis (SPPS), the protection groups fluorenylmethoxycarbonyl (Fmoc) and carbobenzyloxy (Cbz) were applied. Alteration of the amine in the third β

A macrolactonization approach to the total synthesis of the antimicrobial cyclic depsipeptide LI-F04a and diastereoisomeric analogues

• James R. Cochrane,
• Dong Hee Yoon,
• Christopher S. P. McErlean and
• Katrina A. Jolliffe

Beilstein J. Org. Chem. 2012, 8, 1344–1351, doi:10.3762/bjoc.8.154

• epimers (Scheme 1). While macrocyclization to give the core 2 could be performed at any of the amide or ester bonds [10], we chose to use a macrolactonization approach to enable ready access to analogues of the LI-F04a core through straightforward Fmoc solid-phase peptide synthesis of the linear

• which the D-allo-Thr protecting group was either tert-butyl or ΨMe,Me'Pro, respectively, to investigate whether a turn-inducer might assist the macrolactonization reaction. Linear peptides 5 and 6 were prepared by standard Fmoc solid-phase peptide synthesis protocols using PyBOP/Hünigs base as the

• of the crude peptide, so obtained, to authentic samples of both 5 and the C-terminal epimer 9 (which was independently prepared by solid-phase peptide synthesis), indicated that the major product obtained upon macrolactonization of 5 under the Corey–Nicolaou conditions was the undesired cyclic

Synthetic glycopeptides and glycoproteins with applications in biological research

• Ulrika Westerlind

Beilstein J. Org. Chem. 2012, 8, 804–818, doi:10.3762/bjoc.8.90

• backbones, or mimics thereof, offer further possibilities to study protein-binding events. Keywords: glycopeptide binding; glycopeptides; glycoprotein synthesis; solid-phase peptide synthesis; synthetic vaccines; Introduction The majority of human proteins are co- or post-translationally modified by mono

Investigation of the network of preferred interactions in an artificial coiled-coil association using the peptide array technique

• Raheleh Rezaei Araghi,
• Carsten C. Mahrenholz,
• Rudolf Volkmer and
• Beate Koksch

Beilstein J. Org. Chem. 2012, 8, 640–649, doi:10.3762/bjoc.8.71

• three β- and two γ-amino acids, was synthesized by standard solid-phase peptide synthesis and labeled at the N-terminus with the fluorophore 5(6)-tetramethylrhodamine (TAMRA). As described above, the chimera has a modified pentad (β- and γ-amino acids) at the center of its 31-residue sequence (positions

Synthesis of szentiamide, a depsipeptide from entomopathogenic Xenorhabdus szentirmaii with activity against Plasmodium falciparum

• Friederike I. Nollmann,
• Andrea Dowling,
• Marcel Kaiser,
• Klaus Deckmann,
• Sabine Grösch,
• Richard ffrench-Constant and
• Helge B. Bode

Beilstein J. Org. Chem. 2012, 8, 528–533, doi:10.3762/bjoc.8.60

• synthesized using solid-phase peptide synthesis, followed by esterification and subsequent cleavage from the resin, deprotection and cyclization to yield 1, assisted by microwave irradiation at every stage with the exception of the esterification (Scheme 1). In detail, a preloaded 2-chlorotrityl chloride

• protists in order to also understand its molecular function. Experimental Synthesis Unless otherwise stated, we used the chemicals in their highest available purity. The progress of the synthesis was monitored with MALDI–MS as well as RP-UPLC coupled with ESI–MS. Solid-phase peptide synthesis. The linear