Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis

• David C. B. Siebert,
• Roman Sommer,
• Domen Pogorevc,
• Michael Hoffmann,
• Silke C. Wenzel,
• Rolf Müller and
• Alexander Titz

Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286

• , acid-mediated deprotection of the Boc group and final coupling to Boc-ᴅ-alanine. Fully protected tripeptides were transformed by base hydrolysis into the free carboxylic acids, followed by activation of the unprotected C-terminus as a SNAc thioester. Subsequent cleavage of the N-terminal Boc protecting

• benzyl protected serine at the Dha site. Following hydrogenolytic deprotection, in situ produced serine EDC adduct was subjected to copper(I) chloride-mediated elimination to give the dehydroalanine derivatives 34a and 34b in good yields. Deprotection of the ester protecting group also proceeded in good

• hydroxide deprotection of the ester in compound 40 provided the free acrylate 41. In parallel, Boc-protected sarcosine 42 was transformed into the SNAc thioester 43 and the Boc group was removed to give 44. Then, both building blocks, 44 and 41, were coupled to give the protected tripeptide thioester 35b in

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• . Further nucleophilic substitution of 174 with allyltrimethylsilane in the presence of a Lewis acid afforded α-alkylated products 175. The highest de was obtained in the case of 175d. The deprotection of 175 with LAH enabled access to α-alkylated pyrrolidines 176 with the release of 177 (Scheme 56). In

Arylisoquinoline-derived organoboron dyes with a triaryl skeleton show dual fluorescence

• Vânia F. Pais,
• Tristan Neumann,
• Ignacio Vayá,
• M. Consuelo Jiménez,
• Abel Ros and
• Uwe Pischel

Beilstein J. Org. Chem. 2019, 15, 2612–2622, doi:10.3762/bjoc.15.254

• ) group deprotection in MeOH/CH2Cl2 using TsOH·H2O as the catalyst (Scheme 2). In a conventional triflation (Tf2O, DMAP cat.), 7 was converted into 8 with a yield of 86%. For the synthesis the triflates 9–11 a one-pot demethylation–triflation sequence was followed (Scheme 2). The treatment of biaryl

Chemical synthesis of the pentasaccharide repeating unit of the O-specific polysaccharide from Escherichia coli O132 in the form of its 2-aminoethyl glycoside

• Debasish Pal and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2019, 15, 2563–2568, doi:10.3762/bjoc.15.249

• -linked disaccharide (16a) along with 30% β-linked disaccharide (16b). Compound 16a was used for further glycosylation with the trisaccharide acceptor 11 to afford the protected pentasaccharide 17. Once the protected pentasaccharide was at hand, the next challenge was the global deprotection to achieve

Synthesis of novel sulfide-based cyclic peptidomimetic analogues to solonamides

• José Brango-Vanegas,
• Luan A. Martinho,
• Lucinda J. Bessa,
• Andreanne G. Vasconcelos,
• Alexandra Plácido,
• Alex L. Pereira,
• José R. S. A. Leite and
• Angelo H. L. Machado

Beilstein J. Org. Chem. 2019, 15, 2544–2551, doi:10.3762/bjoc.15.247

• ) and their respective carboxylic acids 3 were obtained in good yields based on previously reported procedures (Scheme 2) [35][36]. Starting from Rink Amide AM resin-bound orthogonally protected Fmoc-Cys-(Trt) 4, solonamide analogues were synthesized following stepwise Fmoc deprotection and standard

A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light

• Xavier Gómez-Santacana,
• Sabrina M. de Munnik,
• Tamara A. M. Mocking,
• Niels J. Hauwert,
• Shanliang Sun,
• Prashanna Vijayachandran,
• Iwan J. P. de Esch,
• Henry F. Vischer,
• Maikel Wijtmans and
• Rob Leurs

Beilstein J. Org. Chem. 2019, 15, 2509–2523, doi:10.3762/bjoc.15.244

• in AcOH, completely deprotection took place and, after purification, aniline 30 was obtained with high purity. Compound 30 was used to introduce the iodine atom through a Sandmeyer reaction to give 28e albeit in low yield. Reductive amination with 7 afforded amine 16e followed by methylation to give

In search of visible-light photoresponsive peptide nucleic acids (PNAs) for reversible control of DNA hybridization

• Lei Zhang,
• Greta Linden and
• Olalla Vázquez

Beilstein J. Org. Chem. 2019, 15, 2500–2508, doi:10.3762/bjoc.15.243

• base sensitive compounds, which undergo degradation under standard Fmoc deprotection conditions. As it is common for PNAs, our oligomers have an acetylated N-terminus and a C-terminal carboxamide group. After completion of the PNA sequences, the orthogonally protected backbone module [2-(N-Alloc

Indium-mediated C-allylation of melibiose

• Christian Denner,
• Manuel Gintner,
• Hanspeter Kählig and
• Walther Schmid

Beilstein J. Org. Chem. 2019, 15, 2458–2464, doi:10.3762/bjoc.15.238

• resin followed by filtration and removal of the solvent under reduced pressure, led to precipitation of compound 3-syn, thereby causing problems during the ozonolysis. Thus, dichloromethane was added to the reaction mixture immediately after completed Zemplén-deprotection (as indicated by TLC) without

• Zemplén-deprotection and ozonolysis compound 4-anti was obtained. Purification at this stage utilizing conventional column chromatography was not feasible due to the high polarity of the obtained compound mixture, which contained pyranoid as well as furanoid isomers in their α,β-forms. Thus, per-O

Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids

• Gerardo M. Ojeda,
• Prabhat Ranjan,
• Pavel Fedoseev,
• Lisandra Amable,
• Upendra K. Sharma,
• Daniel G. Rivera and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237

• tetrazole, pyridone or isoquinolone ring. Approaches for the synthesis of tetrazoles and isoquinolones and their interplay as designed in this work. Scope of the Ugi-azide-4CR/deprotection/acylation sequence. Ugi-azide-4CR conducted at the 2.0 mmol scale with tritylamine (1.0 equiv), aldehyde (1.5 equiv

Synthesis of acremines A, B and F and studies on the bisacremines

• Nils Winter and
• Dirk Trauner

Beilstein J. Org. Chem. 2019, 15, 2271–2276, doi:10.3762/bjoc.15.219

• . The use of a chiral oxazaborolidine catalyst led to kinetic resolution and increased the optical purity of 17 to 95% ee. Deprotection of the diol moiety followed by Stille cross coupling with vinyl stannane 18 finally gave 5 in excellent yield (Scheme 2). Since acremine F (5) can be expected to be the

An overview of the cycloaddition chemistry of fulvenes and emerging applications

• Ellen Swan,
• Kirsten Platts and
• Anton Blencowe

Beilstein J. Org. Chem. 2019, 15, 2113–2132, doi:10.3762/bjoc.15.209

•  21) [105][237]. ROMP of the monomers, followed by deprotection yielded facially amphiphilic polynorbornenes that displayed lipid membrane disruption and antimicrobial activities [237][238]. The facially amphiphilic polynorbornenes with pendent ammonium groups were found to disrupt negatively charged

Synthesis of 1-azaspiro[4.4]nonan-1-oxyls via intramolecular 1,3-dipolar cycloaddition

• Yulia V. Khoroshunova,
• Denis A. Morozov,
• Andrey I. Taratayko,
• Polina D. Gladkikh,
• Yuri I. Glazachev and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2019, 15, 2036–2042, doi:10.3762/bjoc.15.200

• group of the cyclopentane ring (Scheme 7). The ester groups in 11a–c were easily cleaved in an aqueous–methanol solution of ammonia. Nitroxides 12a–c were isolated as orange compounds moderately soluble in water. Overall yields of these radicals via the acylation–oxidation–deprotection pathway were in

Norbornadiene-functionalized triazatriangulenium and trioxatriangulenium platforms

• Roland Löw,
• Talina Rusch,
• Tobias Moje,
• Fynn Röhricht,
• Olaf M. Magnussen and
• Rainer Herges

Beilstein J. Org. Chem. 2019, 15, 1815–1821, doi:10.3762/bjoc.15.175

• triazatriangulenium ion 6 was synthesized according to a procedure of Laursen and Krebs [13]. The platform 6 was functionalized with norbornadiene 5 by deprotection of the acetylene with potassium hydroxide and in situ formation of the C–C bond between the acetylene and the central C atom of the platform 6 to yield

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

• derivatives lacking the adamantane moiety, dipeptide 1 with benzyl protection on the C-terminus was obtained after Boc-deprotection as previously reported (Scheme 1) [31]. Peptide 1 was also used for the synthesis of adamantly-containing desmuramyl tripeptide 3. Compound 1 was coupled with previously prepared

• performed. Boc deprotection of obtained compound 6 gave the trifluoroacetic salt of peptide 7 which was used in the synthesis of mannoconjugates. The mannose precursor containing the glycolyl linker 11 was prepared in a three-step procedure shown in Scheme 3. The stereoselective α-anomeric deacetylation of

• peptide moieties. The tert-butyl deprotection was accomplished using a selective reagent, trifluoroacetic acid (TFA). Side products derived from deacetylation of compound 10 have not been detected. The synthesis of benzyl-protected α-mannoside containing a (R)-hydroxyisobutyryl linker was previously

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

• . Acetal formation, reduction of the amide function and deprotection completed synthesis of (−)-hygrine (S)-61. To synthesize (−)-hygroline (2S,2'S)-62 and (−)-pseudohygroline (2S,2'R)-62 the carbonyl group in (S)-66 was reduced and the diastereoisomeric alcohols (2S,2'S)-67 and (2S,2'R)-67 were separated

• transition state was involved. Acid-induced aziridine ring openings and subsequent conjugate additions to the α,β-unsaturated lactone led to the formation of cis-fused [5,5']bicyclic compounds 186a or 186b. Reduction of the lactone moiety in 186a and subsequent deprotection gave (2S,3R,4S,5R)-184. In order

• form a cis-2,6-disubstituted piperidine framework in (2S,3R,6S)-197. N-Methylation of (2S,3R,6S)-197 was accomplished by reductive amination while a selective deprotection provided the hydroxymethyl group in (2S,3R,6S)-198. Swern oxidation, Julia–Kocienski olefination and desilylation gave (−)-(2S,3R

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

Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)

• Małgorzata Urbańczyk,
• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Jerzy Góra,
• Rafał Latajka and
• Norbert Sewald

Beilstein J. Org. Chem. 2019, 15, 1581–1591, doi:10.3762/bjoc.15.162

• , combined with HOAt. Loading of the resin was determined spectrophotometrically by measuring the absorption of the piperidine-dibenzofulvene adduct formed during Fmoc deprotection (20% v/v piperidine in DMF) at wavelength 290 nm. The obtained loadings were ranging from 0.36–0.60 mmol/g, while the original

• ’-tetramethyluronium hexafluorophosphate (HATU, 4 equiv), N,N-diisopropylethylamine (DIEA, 8 equiv) in NMP for 2 hours at room temperature. The loading was analyzed spectrophotometrically by measuring the absorption of the piperidine–dibenzofulvene adduct formed during the Fmoc deprotection (20% v/v piperidine in DMF

• –1.2 equiv) were pre-activated with HATU (2.8 equiv) in DMF and added to the reaction vessel, followed by HOAt (2.25 equiv) and DIEA (2.75 equiv) in DMF. Coupling was carried out at room temperature for 3 hours. After final Fmoc deprotection, the amino groups of peptides were acetylated using acetic

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

• Leticia Monjas,
• Peter Fodran,
• Johanna Kollback,
• Carlo Cassani,
• Thomas Olsson,
• Maja Genheden,
• D. G. Joakim Larsson and
• Carl-Johan Wallentin

Beilstein J. Org. Chem. 2019, 15, 1468–1474, doi:10.3762/bjoc.15.147

• the TBDMS group from the primary to the secondary alcohol was achieved by a protection/deprotection sequence, which smoothly provided alcohol 10 in 71% yield over two steps. A final Swern oxidation gave the building block 3 in 91% yield (33% overall yield from 1,5-pentanediol 6). The other key

• ). Treatment of 18 and 19 with Hoveyda–Grubbs second generation catalyst in refluxing 1,2-dichloroethane afforded the ring-closing metathesis products 20 and 21 in 62% and 45% yield, respectively. Deprotection of the TBDMS group using tetrabutylammonium fluoride followed by final Dess–Martin oxidation gave the

Selenophene-containing heterotriacenes by a C–Se coupling/cyclization reaction

• Pierre-Olivier Schwartz,
• Sebastian Förtsch,
• Astrid Vogt,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2019, 15, 1379–1393, doi:10.3762/bjoc.15.138

• deprotection with TBAF in 66% yield, with selenourea and copper oxide nanoparticles surprisingly did not lead to any targeted DSS 4 in the attempted C–Se cross-coupling reaction. The structures of the prepared novel selenolotriacenes 2–4 and known DTT 1 were characterized by means of NMR spectroscopy

One-pot activation–alkynylation–cyclization synthesis of 1,5-diacyl-5-hydroxypyrazolines in a consecutive three-component fashion

• Christina Görgen,
• Katharina Boden,
• Guido J. Reiss,
• Walter Frank and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2019, 15, 1360–1370, doi:10.3762/bjoc.15.136

• or Brønsted acidic conditions were accompanied by simultaneous deacylation of substituent R3 finally furnishing 5-(hetero)aroyl-3-(hetero)aryl-1H-pyrazole 6a (for attempted dehydrative aromatization, see Supporting Information File 1, Table S5), as already reported for alkaline deprotection

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

• pseudoaxial substituents. The alternative, a more stable transition state formed from the re-face attack would bear to the actually obtained 3S configurated boronic acid analogue 7. The final deprotection of compound 7 by conventional catalytic hydrogenolysis gave the final compound 8 in almost quantitative

• broadening of the H-2, H-3 and H-4 signals suggest a slow equilibrium between different conformations. After deprotection of the benzylidene group in addition to line broadening, signal superposition is observed, hampering any conclusion on the conformation of compound 11. In order to get more information

Ugi reaction-derived prolyl peptide catalysts grafted on the renewable polymer polyfurfuryl alcohol for applications in heterogeneous enamine catalysis

• Alexander F. de la Torre,
• Gabriel S. Scatena,
• Oscar Valdés,
• Daniel G. Rivera and
• Márcio W. Paixão

Beilstein J. Org. Chem. 2019, 15, 1210–1216, doi:10.3762/bjoc.15.118

• organocatalytic performance. Peptides 1 and 2 were subjected to Boc deprotection by treatment with 20% trifluoroacetic acid (TFA) in CHCl3 followed by TFA-catalyzed polymerization in the presence of furfuryl alcohol (10 equiv) according to a literature procedure described for PFA [17] (Scheme 2). The

Alkylation of lithiated dimethyl tartrate acetonide with unactivated alkyl halides and application to an asymmetric synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of squalestatins/zaragozic acids

• Herman O. Sintim,
• Hamad H. Al Mamari,
• Hasanain A. A. Almohseni,
• Younes Fegheh-Hassanpour and
• David M. Hodgson

Beilstein J. Org. Chem. 2019, 15, 1194–1202, doi:10.3762/bjoc.15.116

• % yield [21], gave α-diazo ester 13 in 76% yield following reaction with NaOMe. Furthermore, our earlier racemic model study had established that deprotection and oxidation of a secondary silyl ether in the presence of α-diazo ester functionality was feasible, which constitutes precedent for the

• selective deprotection in α-diazo ester 23 in the presence of the tertiary TBS ether. It was considered important that the tertiary alcohol remain masked during projected oxidation of the released secondary alcohol to give the ketone functionality in the cycloaddition substrate, as otherwise essentially

• circumventing the separate prior desilylation step in our earlier racemic model study [14]. In the event, application of this TES protection approach did provide access to diazo alcohol 27 (Scheme 7). As anticipated from the above deprotection studies with TBDPS ether 23, 1% aq HCl removed both the acetonide

Electrophilic oligodeoxynucleotide synthesis using dM-Dmoc for amino protection

• Shahien Shahsavari,
• Dhananjani N. A. M. Eriyagama,
• Bhaskar Halami,
• Vagarshak Begoyan,
• Marina Tanasova,
• Jinsen Chen and
• Shiyue Fang

Beilstein J. Org. Chem. 2019, 15, 1116–1128, doi:10.3762/bjoc.15.108

• electrophilic oligodeoxynucleotides (ODNs) was achieved using dimethyl-Dmoc (dM-Dmoc) as amino protecting group. Due to the high steric hindrance of the 2-(propan-2-ylidene)-1,3-dithiane side product from deprotection, the use of excess nucleophilic scavengers such as aniline to prevent Michael addition of the

• side product to the deprotected ODN during ODN cleavage and deprotection was no longer needed. The improved technology was demonstrated by the synthesis and characterization of five ODNs including three modified ones. The modified ODNs contained the electrophilic groups ethyl ester, α-chloroamide, and

• be protected as a cyclic acetal instead of the more labile acyclic acetal [5][6]. The maleimide group was incorporated into ODNs as a Diels–Alder adduct with dimethylfuran. Besides the need of an additional step for deprotection, only examples of 5'-end modification was given probably due to the

A chemically contiguous hapten approach for a heroin–fentanyl vaccine

• Yoshihiro Natori,
• Candy S. Hwang,
• Lucy Lin,
• Lauren C. Smith,
• Bin Zhou and
• Kim D. Janda

Beilstein J. Org. Chem. 2019, 15, 1020–1031, doi:10.3762/bjoc.15.100

• , norheroin (1, Figure 3). Thus, norheroin (1) was synthesized according to literature procedure and purified by recrystallization [16]. Alkylation of 1 with tert-butyl bromoacetate and subsequent deprotection with trifluoroacetic acid yielded the N-glycine derivative of norheroin, 16. This critical

• tert-butyl ester protected derivative 4 of the commercially available 4-(4-aminophenyl)butanoic acid was accessed via protection and deprotection of the amine with a phthaloyl group (intermediates 2, 3). Reductive amination of 4 with commercially available phenethylpiperidin-4-one furnished

• respective fentanyl-like domains. Similarly, HF-6, HF-7, HF-9 were obtained by coupling heroin domain 36 to 34, 40, or 47, respectively (Scheme 5). All haptens were synthesized with the carrier protein linker protected as a tert-butyl ester. Deprotection in the presence of trifluoracetic acid unmasked the