Copper-catalyzed asymmetric conjugate addition of organometallic reagents to extended Michael acceptors

• Thibault E. Schmid,
• Sammy Drissi-Amraoui,
• Christophe Crévisy,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2015, 11, 2418–2434, doi:10.3762/bjoc.11.263

• “intermediate” addition products (1,6-adducts when n = 1 and 1,6- and 1,8-adducts when n = 2) was detected in all cases. The nature of the substrate seemed to also have an influence since better results were obtained when the thioester was used as a starting material, in both 1,8- (63% yield, 72% ee) and 1,10

Biocatalysis for the application of CO₂ as a chemical feedstock

• Apostolos Alissandratos and
• Christopher J. Easton

Beilstein J. Org. Chem. 2015, 11, 2370–2387, doi:10.3762/bjoc.11.259

• oxidation to CO2. Acyl-CoA pathways A number of recently elucidated cyclic pathways that exist primarily in archaea initiate through the fixation of CO2 onto acetyl-CoA (10) [51][70], and end with the generation of two equivalents of the starting substrate 10 (Scheme 4). One equivalent of the CoA thioester

Lewis acid-promoted hydrofluorination of alkynyl sulfides to generate α-fluorovinyl thioethers

• Davide Bello and
• David O'Hagan

Beilstein J. Org. Chem. 2015, 11, 1902–1909, doi:10.3762/bjoc.11.205

• thioester enols and enolates, important intermediates in enzymatic C–C bond forming reactions. The method opens access to appropriate analogues for investigations in this direction. Keywords: alkynyl sulfides; α-fluorovinyl thioethers; hydrofluorination; Lewis acids; organofluorine; Introduction

• 5% yield. However, when 1i was reacted with the BF3·Et2O, the starting material was completely consumed in 16 hours, but only traces of the desired compound 2i could be detected, with thioester 5 being the main reaction product (45% yield). An explanation for this behaviour can be drawn from the

• fact that the 4-nitrophenyl group surely must increase the triple bond electrophilicity, hence any trace of water present in the reaction mixture could lead to an intermediate enol thioester which would in turn readily convert to the stable thioester 5. Nonetheless, ensuring rigorously anhydrous

A novel and widespread class of ketosynthase is responsible for the head-to-head condensation of two acyl moieties in bacterial pyrone biosynthesis

• Darko Kresovic,
• Florence Schempp,
• Zakaria Cheikh-Ali and
• Helge B. Bode

Beilstein J. Org. Chem. 2015, 11, 1412–1417, doi:10.3762/bjoc.11.152

• using stable isotope labeled precursors [7] suggested a two-chain biosynthesis mechanism for photopyrone biosynthesis (Scheme 1): First, thioester-activated 9-methyldecanoic acid 14 is covalently bound to an active site cysteine. Deprotonation of the α-carbon of 14 results in the formation of a

• nucleophile, which subsequently attacks the carbonyl carbon of a 5-methyl-3-oxohexanoyl thioester 15, formed by BkdABC [18] to form a new C–C bond. After an additional deprotonation of the bound intermediate 16 the α-pyrone ring is formed and 4 is released from PpyS. The two substrates 14 and 15 might be

One-pot odourless synthesis of thioesters via in situ generation of thiobenzoic acids using benzoic anhydrides and thiourea

• Mohammad Abbasi and
• Reza Khalifeh

Beilstein J. Org. Chem. 2015, 11, 1265–1273, doi:10.3762/bjoc.11.141

• reaction of thiourea with benzoic anhydrides, which were subjected to conjugate addition with electron-deficient alkenes or a nucleophilic displacement reaction with alkyl halides. Keywords: benzoic anhydride; Michael addition; nucleophilic displacement; thioester; thiourea; Introduction Thioesters have

• aqueous Triton X-100 micelle [53]. Alternatively, the thioester could be synthesized from the reaction of the alkyl halide with the thioacid in situ generated from the reaction of thiourea and benzoyl chlorides (Scheme 1, path b). In order to explore this possibility, the alkyl halide was removed from the

• the thioester product cannot be produced through generation of the thioacid from thiourea and benzoyl chloride. To establish a protocol for the one-pot synthesis of thioacid derivatives via in situ generation of thioacids, considerable preliminary tests were accomplished using thiourea and carboxylic

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

• -hydroxypropyl)methacrylamide) (pHPMA) possesses a C2 repeating unit with three fully rotatable bonds, which should convey – compared to the other polymers employed in this study – high backbone flexibility to this carrier. Reactive pHPMA was prepared in a copolymerization of HPMA and the thioester-containing

• building block N-methacryloyl-β-alaninyl-S-benzyl thioester under reversible addition–fragmentation chain-transfer (RAFT) conditions yielding a thioester-containing copolymer with 13.3 kDa and polydispersity of 1.2, which we denominated as NCL-polymer [10]. NCL-polymer was converted into multivalent

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