Trifluoromethyl-substituted tetrathiafulvalenes

• Olivier Jeannin,
• Frédéric Barrière and
• Marc Fourmigué

Beilstein J. Org. Chem. 2015, 11, 647–658, doi:10.3762/bjoc.11.73

• –Blodgett films. The structural and electronic properties of a series of ester [15], thioester [29][30], tertiary amide and thioamide [12] TTF derivatives have been then rationalized, based on: (i) the sizeable contribution of the mesomeric form B (Scheme 1) and, (ii) an ICT from the TTF-based HOMO to the

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

Total synthesis of the proposed structure of astakolactin

• Takayuki Tonoi,
• Keisuke Mameda,
• Moe Fujishiro,
• Yutaka Yoshinaga and
• Isamu Shiina

Beilstein J. Org. Chem. 2014, 10, 2421–2427, doi:10.3762/bjoc.10.252

• diastereoselectivities (90% yield, 83% ee for syn, and 93/7 syn/anti ratio). Next, the transformation to the seco-acid 26 was achieved via successive deprotection of the TBDPS group and the thioester moiety in 25. The lactonization of 26 was then performed in the presence of MNBA and DMAP to afford 1’ with the desired

Investigations of thiol-modified phenol derivatives for the use in thiol–ene photopolymerizations

• Sebastian Reinelt,
• Monir Tabatabai,
• Urs Karl Fischer,
• Norbert Moszner,
• Andreas Utterodt and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 1733–1740, doi:10.3762/bjoc.10.180

• ) to the allyl-modified precursors (7a,b, 12a–c, 15) by use of 2,2’-azobis(2-methylpropionitrile) (AIBN) as the radical source was easily proven by the occurrence of the typical C=O valence vibration of the thioester (9a,b, 13a–c, 16) in the corresponding FTIR spectra at 1684 cm−1 (Figure 1

• ). Additionally, in the range of 6.2 to 4.9 ppm signals corresponding with the presence of a double bond were no longer observed in the 1H NMR spectra. Simultaneously, the appearance of a signal at 2.4 to 2.3 ppm was observed, which corresponds with the methyl group of the thioester (see Figure 2). The thioester

• vibration at approximately 2560 cm−1. Exemplarily, Figure 1 shows a comparison of the FTIR spectra of compound 12b, 13b, and 14b. In Figure 2, a typical 1H NMR spectrum of the thioester 13a and the thiol 14a is shown (further 1H and 13C NMR spectra of all thiols can be found in Supporting Information File 1

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

• -terminus can be modified as hydrazide, alcohol, aldehyde, thioester and many more [22][50]. Furthermore, there are linkers that enable the synthesis of partially and fully protected peptides such as the 2-chlorotrityl resin [51] or the Sieber amide resin [52]. Consequently, the choice of resin and linker

A convenient enantioselective decarboxylative aldol reaction to access chiral α-hydroxy esters using β-keto acids

• Zhiqiang Duan,
• Jianlin Han,
• Ping Qian,
• Zirui Zhang,
• Yi Wang and
• Yi Pan

Beilstein J. Org. Chem. 2014, 10, 969–974, doi:10.3762/bjoc.10.95

• did not improve in the cases of methyl, isopropyl or benzyl esters (Table 2, entries 2–4). The mechanism of the reaction was proposed based on the kinetic studies of the malonic acid half thioester system by Shair [33]. Essentially β-keto acids can undergo decarboxylation or deprotonation to generate

End-group-functionalized poly(N,N-diethylacrylamide) via free-radical chain transfer polymerization: Influence of sulfur oxidation and cyclodextrin on self-organization and cloud points in water

• Sebastian Reinelt,
• Daniel Steinke and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 680–691, doi:10.3762/bjoc.10.61

• allyl bromide (2) and subsequent radical addition of ethanethioic S-acid (4) yielded the corresponding thioesters S-(3-(4-(1,1-dimethylethan-1-yl)phenoxy)propyl) ethanthioate (5a) and S-(3-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)propyl) ethanthioate (5b). The thioester functions were hydrolyzed to obtain

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

• TBS ethers and methyl esters was performed under mildly acidic conditions followed by pig liver esterase-mediated chemoselective hydrolysis. These conditions are compatible with the presence of a coenzyme A or a SNAc thioester, suggesting that they are generally applicable to the synthesis of complex

• carboxylate, which necessitates differentiation of the carboxyl groups at the termini to permit regioselective thioester formation. We decided to avoid late redox transformations. Instead, we achieved differentiation by choice of a chemoselective protection group strategy with removal conditions that are

• conditions. As the presence of a methyl ester would prevent the selective introduction of one thioester into 5a by saponification–thioesterification, we planned transesterification from a suitably activated carboxylic acid derivative 8. Alternatively, direct introduction into 11 with appropriate SNAc

Intermediates in monensin biosynthesis: A late step in biosynthesis of the polyether ionophore monensin is crucial for the integrity of cation binding

• Wolfgang Hüttel,
• Jonathan B. Spencer and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 361–368, doi:10.3762/bjoc.10.34

• the oil-based medium. The yield of isolated dehydroxydemethylmonensin (3) from the double mutant is an order of magnitude lower than the production of monensin from the parent industrial strain, but clearly this precursor, as its ACPX-thioester, is accepted as a substrate by the chain-releasing

• with the polyketide in thioester linkage to a discrete acyl carrier protein (MonACPX) [20], and therefore the terminal carboxylate is not available as an alternative ligand for the bound cation until all the tailoring steps have been accomplished and the mature antibiotic is released by thioesterase

The regulation and biosynthesis of antimycins

• Ryan F. Seipke and
• Matthew I. Hutchings

Beilstein J. Org. Chem. 2013, 9, 2556–2563, doi:10.3762/bjoc.9.290

• , anthranilate is converted to 3-aminosalicylate by a multicomponent oxygenase, AntHIJKL [33][34]. The anthraniloyl-S-AntG carboxylic acid-CoA thioester undergoes a never before seen 1,2-shift. Spiteller and colleagues suggested that AntHIJKL promotes this reaction via an epoxide intermediate similar to a

• , suggesting that these strains produce antimycins with less chemical diversity at the R2 position (Figure 2 and Figure 3). The KS domain catalyses the decarboxylative condensation between the aminoacyl thioester attached to AntCT2 and the 2-carboxy-acyl moiety attached to AntDACP. Next, a discrete

Natural products in synthesis and biosynthesis

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 1897–1898, doi:10.3762/bjoc.9.223

• aminosugar, a hydroxylamine linkage between two sugar subunits, a carbamate, an aromatic iodide, a thioester, and a trisulfide [4]. Natural products have also been used by humankind since ancient times and are part of our traditions and culture, as is evident from the widespread consumption of coffee, tea

Exploration of an epoxidation–ring-opening strategy for the synthesis of lyconadin A and discovery of an unexpected Payne rearrangement

• Brad M. Loertscher,
• Yu Zhang and
• Steven L. Castle

Beilstein J. Org. Chem. 2013, 9, 1179–1184, doi:10.3762/bjoc.9.132

• ]undecanes fused to aromatic rings [11]. Then, we devised an annulation protocol inspired by the work of Donohoe and co-workers [12][13] that provided access to substituted pyridones of the type found in 1 from thioester precursors [14]. Based on these encouraging results, we decided to target lyconadin A

• functional-group manipulations. Based on the aforementioned model study [11], 7-exo–6-exo tandem radical cyclization of phenyl selenoester 4 was expected to produce ketone 3. Disassembly of the pyridone moiety of 4 according to our annulation protocol [14] revealed thioester 5 as a suitable precursor. We

Isotopically labeled sulfur compounds and synthetic selenium and tellurium analogues to study sulfur metabolism in marine bacteria

• Nelson L. Brock,
• Christian A. Citron,
• Claudia Zell,
• Martine Berger,
• Irene Wagner-Döbler,
• Jörn Petersen,
• Thorsten Brinkhoff,
• Meinhard Simon and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 942–950, doi:10.3762/bjoc.9.108

• ][15] followed by its conversion into its CoA-thioester by DmdB and oxidation by the FAD-dependent dehydrogenase DmdC. The addition of water to 3-(methylthio)acryloyl-CoA by the enoyl-CoA hydratase DmdD results in a hemithioacetal, which collapses under release of acetaldehyde, carbon dioxide and MeSH

Quantification of N-acetylcysteamine activated methylmalonate incorporation into polyketide biosynthesis

• Stephan Klopries,
• Uschi Sundermann and
• Frank Schulz

Beilstein J. Org. Chem. 2013, 9, 664–674, doi:10.3762/bjoc.9.75

• the bacterial polyketide fermentation system with tailored synthetic thioester-activated malonates. The membrane permeable N-acetylcysteamine has been proposed as a coenzyme A-mimic for this purpose. Here, the incorporation efficiency into different polyketides of N-acetylcysteamine activated

• by using various different strategies. Subsequently, thioester activated non-native malonate derivatives can be synthesized by additional heterologously expressed biosynthetic pathways leading to the respective derivative of malonyl-CoA [17] or malonyl-ACP [27], which are supplied in vivo to the

• the biosynthetic pathway towards erythromycin in place of the native AT6 domain [39]. This has led to the formation of 2-propargylerythromycin through the incorporation of 2-propargylmalonate into the biosynthetic pathway, activated as SNAC-thioester and supplied to the bacterial fermentation. In this

Efficient Cu-catalyzed base-free C–S coupling under conventional and microwave heating. A simple access to S-heterocycles and sulfides

• Silvia M. Soria-Castro and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2013, 9, 467–475, doi:10.3762/bjoc.9.50

• an undesired hydrolysis of the thioester primary product. Thus, the reaction with a PhI/PhCOSH/Cs2CO3 ratio of 1:1.5:2 afforded Ph2S without traces of the thioester, and with a ratio of 1:1.5:1.5 the PhSCOPh was isolated in only 30% yield. Finally, the formation of PhSCOPh in our hands increased to

• corresponding alkyl halide (0.75 mmol, 1.5 equiv) or KI/I2 (1.5 mmol/0.51 mmol, 3/1.02 equiv) was then added and stirred for 20 min or 24 h, respectively. The work-up of the reactions was similar to that of Method A. For the synthesis of the asymmetric diaryl sulfide, after hydrolysis of the thioester, a second

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

• potent and isoform selective HDAC inhibitor. Here we report our preliminary studies on thioester HDAC inhibitors derived from the active monomeric (thiol) form of psammaplin A, as a means to improve compound delivery into cells. We have discovered that such compounds exhibit both potent cytotoxicity and

• . Keywords: epigenetics; histone deacetylase; natural product; prodrug; psammaplin A; thioester; Introduction Chromatin is a macromolecular complex consisting of DNA, histone and nonhistone proteins. The epigenetic control of chromatin organization plays a major role in the regulation of gene expression

• the cellular levels of reductants such as glutathione [23]. An alternative prodrug approach to “protect” the thiol active form of psammaplin A analogues would be to form the corresponding thioester; the active thiol being generated in cells after cleavage of the acyl group by nonselective esterases

Imidazolinium and amidinium salts as Lewis acid organocatalysts

• Oksana Sereda,
• Nicole Clemens,
• Tatjana Heckel and
• René Wilhelm

Beilstein J. Org. Chem. 2012, 8, 1798–1803, doi:10.3762/bjoc.8.205

• , the model reaction shown in Scheme 2 was evaluated. The α,β-unsaturated thioester 5 was prepared from ethyl cinnamate and 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide (Lawesson’s reagent) [22]. The cycloaddition of ethyl thionocinnamate (5) with 1.5 equiv of cyclopentadiene (2

Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization

• Hiroki Oguri,
• Haruki Mizoguchi,
• Hideaki Oikawa,
• Aki Ishiyama,
• Masato Iwatsuki,
• Kazuhiko Otoguro and
• Satoshi Ōmura

Beilstein J. Org. Chem. 2012, 8, 930–940, doi:10.3762/bjoc.8.105

• followed by enolization and hydrolysis of the thioester yield orsellinic acid (path B). Inspired by this simple yet universal biosynthetic strategy, which generates structural variation among natural products, we envisioned the construction of chemical libraries featuring modular assembly for the rapid

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

• by following literature procedures [22][23][24][25]. In the first step from bis(hydroxymethyl)malonate 38, simple nucleophilic substitution is coupled with an ester hydrolysis and a debrominative decarboxylation. Another nucleophilic substitution with thioacetate converted bromide 39 into thioester

Building photoswitchable 3,4'-AMPB peptides: Probing chemical ligation methods with reducible azobenzene thioesters

• Gehad Zeyat and
• Karola Rück-Braun

Beilstein J. Org. Chem. 2012, 8, 890–896, doi:10.3762/bjoc.8.101

• two regioisomeric azobenzene building blocks 3,4'-AMPB thioester 1b and 4,4'-AMPB thioester 2b were employed in the ligation reactions. While 4,4'-AMPB requires the 4,5,6-trimethoxy-2-mercaptobenzyl auxiliary to minimize reduction of the diazene unit, 3,4'-AMPB can be used in combination with the

• -terminal thioester peptide and either an N-terminal cysteine peptide or Nα-auxiliary-capped peptides. However, for elucidating the complex redox chemistry of the two azobenzene building blocks under the reducing conditions of ligation methods, we solely applied the Boc-protected azobenzene ω-amino acid

• thioesters 1b and 2b instead of a C-terminal thioester peptide. We explored the conventional cysteine-based NCL with Cys-peptide 3, and also screened the application of the TFA-cleavable 4,5,6-trimethoxy-2-mercaptobenzyl (Tmb) and 1-(2,4-dimethoxyphenyl)-2-mercaptoethyl auxiliaries by using peptides 4 and 5

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

• synthetic glycoproteins. Since the discovery of native chemical ligation (NCL) by Kent and co-workers, numerous efforts have been made to prepare challenging protein targets [39][40][41][42][43][44]. In the NCL method, a native amide bond is formed by coupling of a C-terminal thioester with the N-terminal

• Fmoc-SPPS followed by sequential NCL [51]. The N-glycopeptide fragment RNase 26–39 (17) was prepared with a thioester in the C-terminal and a thiazolidine protected cysteine at the N-terminus. The chemical ligation was performed by coupling of the N-glycopeptide thioester RNase 26–39 (17) and the

• RNase fragment 26–124 (20) to the thioester peptide fragment RNase 1-25 (21) was followed to give RNase fragment 1–124 (22). The formed RNase C protein was then folded by treatment with glutathione disulfide (GSSG) resulting in an active RNase C enzyme (23) (Scheme 3). Recently, the 111-amino-acid long

Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes

• Jan-Christoph Kehr,
• Douglas Gatte Picchi and
• Elke Dittmann

Beilstein J. Org. Chem. 2011, 7, 1622–1635, doi:10.3762/bjoc.7.191

• Claisen-type cyclization step to form the characteristic bicyclic ring structure of anatoxin while the growing chain is tethered to the AnaF ACP domain. Experimental evidence for this suggestion is currently lacking. Finally, the bicyclic thioester is suggested to be transferred to the polyketide synthase

• biosynthesis include a six-carbon carboxylic acid unit as starter moiety. In vitro studies revealed the activation of either hexanoic, hexenoic or hexynoic acids at the JamA enzyme, whereas bromination clearly succeeded thioester formation [43]. Curacin A Curacin A (9) was originally isolated from a Lyngbya

• halogenation domain, although this could not be expected from the structure of curacin A. In vitro studies revealed that indeed cyclopropyl ring formation is preceded by a halogenation step (Figure 6B) [42]. The Cur ECH2 was found to catalyze the formation of a α,β-enoyl thioester, which is in contrast to the

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33