Peptide–polymer ligands for a tandem WW-domain, an adaptive multivalent protein–protein interaction: lessons on the thermodynamic fitness of flexible ligands

• Katharina Koschek,
• Vedat Durmaz,
• Oxana Krylova,
• Marek Wieczorek,
• Shilpi Gupta,
• Martin Richter,
• Alexander Bujotzek,
• Christina Fischer,
• Rainer Haag,
• Christian Freund,
• Marcus Weber and
• Jörg Rademann

Beilstein J. Org. Chem. 2015, 11, 837–847, doi:10.3762/bjoc.11.93

• ) was further converted by condensation with 2-N-maleimido-ethylamine and N-ethyl-N´-dimethylaminopropylcarbodiimide (EDC) [6]. The monovalent ligand peptide 2 was attached to the dextran carriers by nucleophilic addition of the thiols to the maleimide double bond furnishing peptide–polymer conjugates

Synthesis of tripodal catecholates and their immobilization on zinc oxide nanoparticles

• Franziska Klitsche,
• Julian Ramcke,
• Julia Migenda,
• Andreas Hensel,
• Tobias Vossmeyer,
• Horst Weller,
• Silvia Gross and
• Wolfgang Maison

Beilstein J. Org. Chem. 2015, 11, 678–686, doi:10.3762/bjoc.11.77

• as a cheap starting material [43]. Amine 1 was coupled to a commercially available PEG-carboxylate (5 kDa) with EDC/DMAP. The resulting PEG-conjugate was treated with KOTMS to remove the methyl esters to give tricarboxylic acid 2 in good 57% yield for the two-step procedure. In a last step, dopamine

• chloride to give acrylamide 4. Treatment of 4 with dimethylamine and excess KOH leads to the nucleophilic addition of the amine and saponification of the methyl esters in one step to give the free acid 5 after acidic work-up. Subsequent coupling of 5 to dopamine acetonide 6 with EDC and HOBt gave the

• times. Synthesis of tripodal catecholates for surface immobilization. PEG-triscatecholate 3 was synthesized from 1 according to literature [31]. Abbreviations: PEG = poly(ethylene glycol) (5 kDa); EDC = 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; DMAP = 4-(dimethylamino)pyridine; HOBt

Formation of nanoparticles by cooperative inclusion between (S)-camptothecin-modified dextrans and β-cyclodextrin polymers

• Thorbjørn Terndrup Nielsen,
• Catherine Amiel,
• Laurent Duroux,
• Kim Lambertsen Larsen,
• Lars Wagner Städe,
• Reinhard Wimmer and
• Véronique Wintgens

Beilstein J. Org. Chem. 2015, 11, 147–154, doi:10.3762/bjoc.11.14

• the 100 nm range of potential biomedical interest. Results and Discussion CPT-dextrans Synthesis The synthesis of CPT-dextrans was achieved in two steps. First azide-modified CPT (N3CPT) was synthesized by esterification with 6-azidohexanoic acid mediated by EDC/DMAP (Scheme 1). TLC showed complete

• tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine (TBTA) [20] were prepared according to literature. (S)-Camptothecin >95.0% was obtained from TCI Japan. Ambersep GT74 resin, anhydrous dichloromethane (DCM) ≥99.8%, N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC) ≥99.0%, 4

• EDC (982 mg, 5.02 mmol) were added and the solution was stirred at rt overnight. TLC showed complete conversion of the CPT and the solution was washed with water (3 × 100 mL), brine (100 mL) and dried over magnesium sulfate. The solution was filtered, concentrated to approx. 10 mL in vacuo and

Enantioselective synthesis of polyhydroxyindolizidinone and quinolizidinone derivatives from a common precursor

• Nemai Saha and
• Shital K. Chattopadhyay

Beilstein J. Org. Chem. 2014, 10, 3104–3110, doi:10.3762/bjoc.10.327

• unsaturated amide 9 in readiness for a subsequent RCM reaction. Ring closure of 9 proceeded better in the presence of Grubbs’ second generation catalyst [34] to provide the indolizidine derivative 10 in good yield. Similarly, treatment of amine 8 with vinylacetic acid in the presence of EDC/HOBt under

• ) for compound 15. 1H,1H COSY spectrum of compound 15. Selected nOe correlations and part NOESY spectrum of compound 23 in D2O (600 MHz). Reagents and conditions: (i) Zn/AcOH, rt, 1 h, 86%. (ii) TBSOTf, DIPEA, CH2Cl2, −5 °C, 1 h, 91%. (iii) Acrylic acid, EDC, HOBt, NMM, CH2Cl2, 0 °C to rt, 6 h, 96%. (iv

• ) G-II (8 mol %), benzene, reflux, 24 h, 75%. (v) Vinyl acetic acid, EDC, HOBt, NMM, CH2Cl2, 0 °C to rt, 10 h, 90%. (vi) G-II (3 mol %), benzene, 50 °C, 2 h, 95%. Reagents and conditions: (i) OsO4, NMO, acetone/water, rt, 12 h, 96%. (ii) NaH, THF, BnBr, Bu4NI, 0 °C to rt, 6 h, 70%. (iii) Ac2O

(2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues

• Armin de Meijere,
• Sergei I. Kozhushkov,
• Dmitrii S. Yufit,
• Christian Grosse,
• Marcel Kaiser and
• Vitaly A. Raev

Beilstein J. Org. Chem. 2014, 10, 2844–2857, doi:10.3762/bjoc.10.302

• '-nitrocyclopropyl)alanine and the 3-(2'-fluoromethylcyclopropyl)alanines, HATU as well as the combination of EDC and 7-aza-1-hydroxybenzotriazole (HOAt) [61] were used for each condensation step to ensure high yields. The most unusual fragment in hormaomycin (1) and its analogues is the ester bond between the

• '-fluoromethylcyclopropyl)alanine residues. a: trifluoromethyl-, b: difluoromethyl-, c: monofluoromethylcyclopropylalanine. Reagents and conditions: i) oxalyl chloride, pyridine/dicyclopropylmethanol, DMAP, CH2Cl2, 0→20 °C, 20 h; ii) ZOSu, NaHCO3, acetone/water, 2 h; iii) 50% Et2NH/THF, 20 °C, 1 h; iv) EDC, HOAt, 2,4,6

• -collidine, CH2Cl2, 4→20 °C, 14 h; v) FmocOSu, NaHCO3, acetone/water, 3 h; vi) H2, Pd/C, EtOAc, 20 °C, 2 h; vii) MeZOSu, NaHCO3, water/dioxane, 20 °C, 3 h; viii) All-Br, K2CO3, MeCN, 85 °C, 3 h, 60 °C, 16 h; ix) EDC, 4-pyrrolidinopyridine, CH2Cl2, 4→20 °C, 16 h; x) [Pd(PPh3)4], N-methylaniline, DME, 20 °C, 1

Detonation nanodiamonds biofunctionalization and immobilization to titanium alloy surfaces as first steps towards medical application

• Juliana P. L. Gonçalves,
• Afnan Q. Shaikh,
• Manuela Reitzig,
• Daria A. Kovalenko,
• Jan Michael,
• René Beutner,
• Gianaurelio Cuniberti,
• Dieter Scharnweber and
• Jörg Opitz

Beilstein J. Org. Chem. 2014, 10, 2765–2773, doi:10.3762/bjoc.10.293

• of MES containg 6 mg of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC). The mixture was stirred for 20 min at room temperature. Afterwards, 25 mL of O-phosphorylethanolamine (8% aqueous) solution was added to the activated particles and the suspension was stirred for 2.5 h at room temperature

• centrifuged to prepare the washing step with 40 mL of acetone for 24 h at 40 °C. The sample 5 was then dried under vacuum. Silanized DND functionalized with O-phosphorylethanolamine 200 mg of silanized DND 5, 80 mg of O-phosphorylethanolamine, 35 mg of DMAP, 50 mg of EDC and 20 mL of dichloromethane (DCM

• -phosphorylethanolamine (O-PEA), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), 2-(N-morpholinoethanesulfonic acid), room temperature, 2.5 h; (iii) Sodium borohydride, ethanol, 60 °C, 24 h, (iv) (3-aminopropyltrimethoxysilane (APTMS), acidic environment, room temperature, 48 h, (v) O-PEA, EDC, 4-(dimethylamino

Synthesis and biological evaluation of novel N-α-haloacylated homoserine lactones as quorum sensing modulators

• Michail Syrpas,
• Ewout Ruysbergh,
• Christian V. Stevens,
• Norbert De Kimpe and
• Sven Mangelinckx

Beilstein J. Org. Chem. 2014, 10, 2539–2549, doi:10.3762/bjoc.10.265

• thionyl chloride [27]. These reaction conditions allowed the synthesis of α-brominated fatty acids 5 in a highly selective and efficient manner. Brominated AHL analogues 6a–f (dr 1:1) were prepared in acceptable yields by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)-mediated coupling of the

Clicked and long spaced galactosyl- and lactosylcalix[4]arenes: new multivalent galectin-3 ligands

• Silvia Bernardi,
• Paola Fezzardi,
• Gabriele Rispoli,
• Stefania E. Sestito,
• Francesco Peri,
• Francesco Sansone and
• Alessandro Casnati

Beilstein J. Org. Chem. 2014, 10, 1672–1680, doi:10.3762/bjoc.10.175

• to the concurrent formation of dicyclohexylurea (DCU), several purification steps were necessary to obtain pure calix[4]arene 8. The use of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) as an alternative coupling agent allowed us to isolate pure compound 8 in a more straightforward way and

• substitution reaction of chloride with NaN3 (Scheme 3) led to the corresponding azido derivative 15, which was used to “click” both the cone (8) and 1,3-alternate (18) pentynoic amides. Compound 18 was obtained from the corresponding 1,3-alternate p-aminocalix[4]arene 17 [47] by a reaction with EDC in CH2Cl2

• the cone galactosylcalix[4]arenes 1. Reaction conditions: (i) DCC, DMAP, CH2Cl2, under reflux, 5 h, 44%; (ii) EDC, CH2Cl2/py (7:3), rt, 18 h, 66%; (iii) CuSO4·5H2O, Na-ascorbate, DMF/H2O, μW (150 W), 80 °C, 20 min, 83%; (iv) CH3ONa, CH3OH, rt, 1 h – IR120/H+, rt, 30 min, quantitative. Synthesis of the

Pyrene-modified PNAs: Stacking interactions and selective excimer emission in PNA₂DNA triplexes

• Alex Manicardi,
• Lucia Guidi,
• Alice Ghidini and
• Roberto Corradini

Beilstein J. Org. Chem. 2014, 10, 1495–1503, doi:10.3762/bjoc.10.154

• acid 5, and linked to the Fmoc-protected PNA backbone using EDC/DhBtOH as activating mixture; the PNA monomer 1, was then obtained by ester hydrolysis of 6 under acidic conditions. The PNAs sequence was designed to be complementary to the W1282X mutated form of CFTR gene, and all PNAs were synthesized

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

• , quant.; c) CSA, PhCH(OMe)2, MeCN, DMF, 86%; d) (S)-2-chloropropionic acid, NaH, 1,4-dioxane, 93%; e) Boc2O, NH4HCO3, pyridine, 1,4-dioxane, 99%; f) 1) DBU, HOBt, DCM; 2) Fmoc-L-Ala-OH, EDC, DIPEA, DCM, 82%; g) 1) 13, DBU, HOBt, DCM; 2) 12, HATU, DIPEA, DCM, 70%; h) 1) Me3P (solution in THF), DMF, THF

Glycosystems in nanotechnology: Gold glyconanoparticles as carrier for anti-HIV prodrugs

• Fabrizio Chiodo,
• Marco Marradi,
• Javier Calvo,
• Eloisa Yuste and
• Soledad Penadés

Beilstein J. Org. Chem. 2014, 10, 1339–1346, doi:10.3762/bjoc.10.136

• thioacetate [31], was reacted with ABC and 3TC in DMF in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and 4-dimethylaminopyridine (DMAP) to obtain the ester derivative in ~75% yield. After purification, the protecting group of the thiol was removed with hydrazine acetate to give the

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

• 3 steps from 17). The potential of 19 to serve as a universal building block for C-terminal derivatization was demonstrated by the following transformations. Acid 19 was reacted with 1,1-diethoxy-3-aminopropane (20) under standard EDC/HOBt coupling conditions to afford amide 21 in 77% yield

Synthesis of complex intermediates for the study of a dehydratase from borrelidin biosynthesis

• Frank Hahn,
• Nadine Kandziora,
• Steffen Friedrich and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 634–640, doi:10.3762/bjoc.10.55

• , NaH, THF, 0 °C, 3 h (18% over two steps from 12) or 26, CH2Cl2, 50 °C, 21 h (64% over two steps from 12); e) 27, 18-crown-6, K2CO3, THF, −20 °C then 0 °C for 5 h (47% over two steps from 12); f) HSNAc, EDC, DMAP, CH2Cl2, rt, 16 h (78%); g) PPh3, H2O, 70 °C, 11 h, then NaOH, rt (64%). Supporting

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

A unified approach to the important protein kinase inhibitor balanol and a proposed analogue

• Tapan Saha,
• Ratnava Maitra and
• Shital K. Chattopadhyay

Beilstein J. Org. Chem. 2013, 9, 2910–2915, doi:10.3762/bjoc.9.327

• group in the latter was executed under standard conditions to provide amine 28. This was then coupled with 4-benzyloxybenzoic acid using EDC as activating agent to obtain the corresponding amide derivative 29 in an overall yield of 20% over eleven steps from 17. The stereochemical identity of this

Charge-transfer interaction mediated organogels from 18β-glycyrrhetinic acid appended pyrene

• Jun Hu,
• Jindan Wu,
• Qian Wang and
• Yong Ju

Beilstein J. Org. Chem. 2013, 9, 2877–2885, doi:10.3762/bjoc.9.324

• method 1-Pyrenemethylamine hydrochloride (95%), 18β-glycyrrhetinic acid (GA, 97%), 4-dimethylaminopyridine (DMAP, 99%), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC, 99%), 9-fluorenone (98%) are purchased from Sigma-Aldrich, and used as received. All organic solvents were dried and distilled before

• pyrene 3 To a solution of 1-pyrenemethylamine hydrochloride (113 mg, 0.42 mmol), 4-dimethylaminopyridine (DMAP, 52 mg, 0.42 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC, 135 mg, 0.42 mmol) in dry dichloromethane (DCM, 30 mL), 18β-glycyrrhetinic acid (GA, 200 mg, 0.42 mmol) was added

• -dimethylaminopropyl)carbodiimide (EDC), dichloromethane (DCM), room temperature, 72%; (b) HNO3, H2SO4, 70 °C, 93%. Gelation test results of GA-pyrene (3) with TNF (4, molar ratio =1:1). Thermodynamic parameters (ΔH°, ΔS°, and ΔG°) of CT gel (3 and 4, 1:1, molar ratio) in various solvents at 298 K. Supporting

Synthesis of the reported structure of piperazirum using a nitro-Mannich reaction as the key stereochemical determining step

• James C. Anderson,
• Andreas S. Kalogirou,
• Michael J. Porter and
• Graham J. Tizzard

Beilstein J. Org. Chem. 2013, 9, 1737–1744, doi:10.3762/bjoc.9.200

• contrast, the reaction of carboxylic acid 11 with diamine 21, in the presence of EDC (1.50 equiv) and 1-hydroxybenzotriazole (1.50 equiv) at rt, gave the desired product 23 in good yield (Scheme 6) [57]. The double bond geometry was assigned as Z by NOESY 1H NMR and probably results from steric inhibition

• , 264.2196; found, 264.2201. (5S*,6R*,Z)-5-Isobutyl-6-isopropyl-4-(4-methoxyphenyl)-3-(2-methylpropylidene)piperazin-2-one (23): To a solution of diamine 21 (61 mg, 0.23 mmol) in THF (5 mL) was added N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC, 67 mg, 0.35 mmol) and 1

• , CF3CO2H, −78 °C, dr >95:5; (b) Zn, 6 M HCl, EtOAc/EtOH, rt, single diastereoisomer; (c) CSCl2, aq NaHCO3 CH2Cl2/ MeOH, rt. (a) (COCl)2, DMF, CH2Cl2, rt; (b) 21, Py, DMAP, CH2Cl2, rt; (c) EDC, HOBt, THF/CH2Cl2, rt; (d) H2 (1 atm), Pd/C, MeOH, rt; (e) CAN, MeCN/H2O, 0 °C; (f) 4 M HCl in dioxane, MeCN/Et2O

Design and synthesis of tag-free photoprobes for the identification of the molecular target for CCG-1423, a novel inhibitor of the Rho/MKL1/SRF signaling pathway

• Jessica L. Bell,
• Andrew J. Haak,
• Susan M. Wade,
• Yihan Sun,
• Richard R. Neubig and
• Scott D. Larsen

Beilstein J. Org. Chem. 2013, 9, 966–973, doi:10.3762/bjoc.9.111

• acid (4) was reacted with substituted anilines 5 under standard EDC-mediated amidation conditions, followed by TFA-catalyzed deprotection to afford amides 6. A subsequent second amidation with benzoic acids 7 afforded final bis(amide) analogues 8. We also synthesized a model azide (Scheme 2). Synthesis

Thioester derivatives of the natural product psammaplin A as potent histone deacetylase inhibitors

• Matthias G. J. Baud,
• Thomas Leiser,
• Vanessa Petrucci,
• Mekala Gunaratnam,
• Stephen Neidle,
• Franz-Josef Meyer-Almes and
• Matthew J. Fuchter

Beilstein J. Org. Chem. 2013, 9, 81–88, doi:10.3762/bjoc.9.11

• functionalities in order to allow comparison of our data to our previously generated in vitro and in cell SAR data [20]. Condensation between acid 5 and O-methylhydroxylamine, followed by EDC coupling with S-2-aminoethyl ethanethioate 6 [26] afforded thioacetate analogue 7 (Scheme 2). Condensation of acid 5 with

• psammaplin A against zinc-dependant HDACs. Adapted from Baud et al. [20]. Synthesis of 7–9. Conditions: (i) HCl·H2NOMe, pyridine, rt, 12 h; (ii) EDC, NHS, dioxane, rt, 3 h; (iii) 6, Et3N, dioxane/MeOH, rt; (iv) HCl·H2NOH, pyridine, rt, 12 h; (v) DCC, NOHP, 6, Et3N, dioxane, rt, 24 h. Top: Generation of 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

• of the 1–8 and the thionated 9–11 segments. For the difficult coupling steps, in particular those involving the segment condensations, the N-[3-(dimethylamino)-propyl]-N'-ethylcarbodiimide (EDC)/7-aza-1-hydroxy-1,2,3-benzotriazole (HOAt) [51] activating method was used, while the EDC/1-hydroxy-1,2,3

• highlighted in color. Ribbon representation of the lowest energy (138.7 kcal/mol) 3D structure obtained for ψ[CS-NH]9. All amino acid side chains are shown. The yellow atom on Gly9 refers to sulfur. Synthesis of ψ[CS-NH]2. 1: Coupling in the presence of EDC/HOBt. 2: Deprotection by using TFA/DCM. 3

• : Deprotection by catalytic hydrogenation with Pd/C. 4: Thionation with Lawesson's reagent in THF. 5: Coupling with n-Oct-OH in the presence of EDC/HOBt. 6: Saponification with NaOH/MeOH. 7: Coupling in the presence of EDC/HOAt. Synthesis of ψ[CS-NH]5. 1: Coupling in the presence of EDC/HOBt. 2: Deprotection by

Multistep organic synthesis of modular photosystems

• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2012, 8, 897–904, doi:10.3762/bjoc.8.102

• diphosphonates in NDI 24 gave 18, which was reacted in situ with NDI 12 to yield initiator 2. Synthesis of propagators The synthesis of propagator 3 starts with NDA 13 as well (Scheme 2). Diimidation with Cbz-protected lysine 25 gave the diacid 26. Activation with EDC, HOBt and TEA was followed by the reaction

• . Reaction of EDC-activated diacid 35 with tert-butyl carbazate followed by deprotection of the obtained cNDI 36 and coupling with activated asparagusic acid 28 gave cNDI 37. Hydrazide deprotection quenched by benzaldehyde 30 gave the yellow cNDI propagator 4. The activated asparagusic acid 28 was prepared

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

• -methylmorpholine (NMM) at 4 °C, affording the synthetic intermediate 4. The attempts to form the ester bond by using catalytic amounts of 4-dimethylaminopyridine (DMAP) with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), DMAP together with N,N′-diisopropylcarbodiimide (DIC), or a mixture of the DMAP

Azobenzene dye-coupled quadruply hydrogen-bonding modules as colorimetric indicators for supramolecular interactions

• Yagang Zhang and
• Steven C. Zimmerman

Beilstein J. Org. Chem. 2012, 8, 486–495, doi:10.3762/bjoc.8.55

• (DeUG) is described. The coupling of azobenzene dye 2 to mono-amido DAN units 4, 7, and 9 was effected by classic 4-(dimethylamino)pyridine (DMAP)-catalyzed peptide synthesis with N-(3-dimethylaminopropyl)-N’-ethyl carbodiimide hydrochloride (EDC) as activating agent, affording the respective amide

• -ethylcarbodiimide hydrochloride (EDC) was used as an activating agent and 4-(dimethylamino)pyridine (DMAP) was used as a catalyst [49]. Azobenzene–DAN conjugate 5 was obtained in 71% yield as an orange–red solid following chromatography. Deprotection of azobenzene 2 under mildly basic conditions was also

• EDC and DMAP in methylene chloride, and the orange–yellow product 12 was isolated in a relatively low 35% yield (Scheme 3). No attempt was made to optimize the coupling conditions; instead, attention was turned to the possibility of coupling the partners by using the copper-catalyzed azide–alkyne

Synthesis of multivalent host and guest molecules for the construction of multithreaded diamide pseudorotaxanes

• Nora L. Löw,
• Egor V. Dzyuba,
• Boris Brusilowskij,
• Lena Kaufmann,
• Elisa Franzmann,
• Wolfgang Maison,
• Emily Brandt,
• Daniel Aicher,
• Arno Wiehe and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2012, 8, 234–245, doi:10.3762/bjoc.8.24

• synthesis of the iodo-substituted monovalent diamide axle centerpiece 2 was realized by the four-step synthesis shown in Scheme 1. The free amino group in mono-Cbz-protected N,N'-dimethylethylene diamine 3 [105] was elongated with the commercially available N-Boc-protected β-alanine 4 in the presence of EDC

• Sonogashira coupling to the appropriate spacers: (a) EDC, HOBt, DMF, 22 h, 92%; (b) H2, Pd/C, EtOH, 3 d, 98%; (c) EDC.HCl, HOBt, DMF, 24 h, 73%; (d) I2, PIDA, AcOH/Ac2O, 1 h, 67%; (EDC = 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, HOBt = 1-hydroxybenzotriazole, DMF = N,N'-dimethylformamide, PIDA

Synthesis of enantiomerically enriched (R)-¹³C-labelled 2-aminoisobutyric acid (Aib) by conformational memory in the alkylation of a derivative of L-alanine

• Stephen P. Fletcher,
• Jordi Solà,
• Dean Holt,
• Robert A. Brown and
• Jonathan Clayden

Beilstein J. Org. Chem. 2011, 7, 1304–1309, doi:10.3762/bjoc.7.152

• formation of pairs of diastereoisomeric dipeptides from small aliquots of 6* with an excess of Cbz-L-Phe, EDC and HOBt (Scheme 2). The ratio of diastereoisomers was determined by comparison of the peak heights of the two 13C signals by 13C NMR (Figure 2). As shown in Table 1, the d.r. of 7 (and hence the

• of Cbz-L-phenylalanine (40 mg, 0.13 mmol), HOBt (20 mg, 0.2 mmol), EDC (0.03 mL, 0.2 mmol) and Et3N (0.3 mL) were added to a suspension of 6* (4 mg, 0.03 mmol) in CH2Cl2 (4 mL). The resulting solution was stirred overnight at room temperature and partitioned between water and ethyl acetate. The