Genome mining in Trichoderma viride J1-030: discovery and identification of novel sesquiterpene synthase and its products

• Xiang Sun,
• You-Sheng Cai,
• Yujie Yuan,
• Guangkai Bian,
• Ziling Ye,
• Zixin Deng and
• Tiangang Liu

Beilstein J. Org. Chem. 2019, 15, 2052–2058, doi:10.3762/bjoc.15.202

• 5/6 bicyclic sesquiterpene with the molecular formula C15H26O (Figure 1). Interestingly, compound 1 contained a quaternary carbon with two methyl groups, which is uncommon for the cyclization mechanism of sesquiterpenoids and needs further investigation. Compound 2 was purified as a white powder. 1H

• characterised as a 5/6 bicyclic sesquiterpene compound 1 oxygenated at C-11. Interestingly, esterified compound 1 was isolated during the product extraction process, suggesting an esterification reaction. It contained a quaternary carbon with two methyl groups, which is uncommon of the cyclization mechanism of

Bipolenins K–N: New sesquiterpenoids from the fungal plant pathogen Bipolaris sorokiniana

• Chin-Soon Phan,
• Hang Li,
• Simon Kessler,
• Peter S. Solomon,
• Andrew M. Piggott and
• Yit-Heng Chooi

Beilstein J. Org. Chem. 2019, 15, 2020–2028, doi:10.3762/bjoc.15.198

• , 1.88, 2.65 and 3.77), which are typical resonances for sativene-type sesquiterpenoids. The NMR data for 1 were very similar to those for prehelminthosporol lactone (5) except for the replacement of a methine group (δC 32.1; δH 1.42) at C-9 in 5 with a hydroxylated quaternary carbon (δC 73.1) in 1. This

• quaternary carbon (δC 74.8) in 3. This suggested that 3 was the 6-hydroxy analogue of 5, which was further confirmed by detailed analysis of key 2D NMR correlations (Figure 2). The absolute configurations of the stereocentres in 3 were established to be identical to 1 and 2 based on the analysis of proton

• revealed the absence of ester and alkene resonances and the presence of three hydroxylated methylenes at C-12 (δC 62.2; δH 3.79 and 3.65), C-14 (δC 69.8; δH 3.90 and 3.36) and C-15 (δC 62.9; δH 3.77 and 3.47), and one hydroxylated quaternary carbon at C-2 (δC 88.1). This suggested 4 was related to 5, but

Different reactivity of phosphorylallenes under the action of Brønsted or Lewis acids: a crucial role of involvement of the P=O group in intra- or intermolecular interactions at the formation of cationic intermediates

• Stanislav V. Lozovskiy,
• Alexander Yu. Ivanov and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1491–1504, doi:10.3762/bjoc.15.151

• –8.07 ppm, the signal of vinyl carbon C4 at 166.8–171.9 ppm, and the signal of quaternary carbon C5 at 96.0–116.3 ppm. It is worth noting that 2,2-dichloro (A, B) and 2,2-diarylsulfanyl (F, G)-substituted cations exhibit down field shifted signals in the 31P NMR (δ 87.82–115.37 ppm) in comparison with

• spectrum for species E4. Apart from that, in 13C NMR spectra, the signals of quaternary carbon bearing two methyl groups in E2 and E4 are very close (δ 70.3–70.9 ppm, see Scheme 1). Contrary to that, the signal of this carbon for E2 is very much down field shifted (δ 96.1 ppm). This indicates that in

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• afford polysubstituted cyclopropanols (or cyclopropylamines) potentially bearing several diastereo- and enantiomerically enriched adjacent stereogenic centers, including quaternary carbon stereocenters, as single diastereo- and enantiomer from a simple precursor, it would certainly provide an additional

• when the same sequence of diastereoselective carbometalation/oxidation was performed on cyclopropenyl ester 1, the in situ-formed donor–acceptor cyclopropanol undergoes a selective ring-opening to provide the acyclic product possessing a quaternary carbon stereocenter [57]. As the enantioselective

• the oxidation of the cyclopropylcopper species proceeded equally well and gave the corresponding cyclopropanols possessing two adjacent quaternary carbon stereocenters (7i–r) in good yields and excellent diastereomeric ratios. Here again, the methyl, the alkyl group from the organometallic and the

New sesquiterpenoids from the South China Sea soft corals Clavularia viridis and Lemnalia flava

• Qihao Wu,
• Yuan Gao,
• Meng-Meng Zhang,
• Li Sheng,
• Jia Li,
• Xu-Wen Li,
• Hong Wang and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2019, 15, 695–702, doi:10.3762/bjoc.15.64

• sp3 quaternary carbon, three sp2 methines, and five sp2 quaternary carbons (Table 1). The typical resonances at δC 145.6, δC 113.0, δH/C 7.30/136.8, δC 123.4, δC 153.0, δH/C 6.71/116.8 revealed the presence of a 1,2,4,5-tetrasubstituted benzene ring, and the signals at δH/C 6.08/99.1, δC 154.2

Synthesis of cis-hydrindan-2,4-diones bearing an all-carbon quaternary center by a Danheiser annulation

• Gisela V. Saborit,
• Carlos Cativiela,
• Ana I. Jiménez,
• Josep Bonjoch and
• Ben Bradshaw

Beilstein J. Org. Chem. 2018, 14, 2597–2601, doi:10.3762/bjoc.14.237

• relative configuration of the major epimer of 8 (Figure 3) was established on the basis of a cross peak in the NOESY spectrum that correlated the methyl group at C3 with a methylene proton adjacent to the quaternary carbon of the side chain at C3a. The configuration at C3, adjacent to a carbonyl group, is

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• TAN1251A, TAN1251C and TAN1251D [86]. Wardrop and Burge [87] reported a iodine(III)-mediated oxidative spirocyclization of hydroxamates 50. The azaspirans 51 containing quaternary carbon centers were synthesized in good to excellent yields on treating substrates 50 with PIFA (31) in dichloromethane

Hypervalent iodine(III)-mediated decarboxylative acetoxylation at tertiary and benzylic carbon centers

• Kensuke Kiyokawa,
• Daichi Okumatsu and
• Satoshi Minakata

Beilstein J. Org. Chem. 2018, 14, 1046–1050, doi:10.3762/bjoc.14.92

• applications have not been explored. We recently reported on the decarboxylative Ritter-type amination of carboxylic acids containing an α-quaternary carbon center using a combination of PhI(OAc)2 and I2 to produce the corresponding α-tertiary amine derivatives (Scheme 1) [25]. Mechanistic investigations

• reaction, namely acetoxylation, via the oxidative displacement of an iodine atom of the in situ generated alkyl iodide by PhI(OAc)2 [26]. Herein, we report on the decarboxylative acetoxylation of carboxylic acids that contain an α-quaternary carbon center using PhI(OAc)2 and I2 in a CH2Cl2/AcOH mixed

• containing α-quaternary carbon centers were efficiently converted into the corresponding acetates under mild reaction conditions [27]. Various functional groups, including bromo (2a and 2f), fluoro (2b), carboxyl (2e), nitro (2g), and ester (2h) groups, were all well tolerated, providing the corresponding

Methyl isocyanide as a convertible functional group for the synthesis of spirocyclic oxindole γ-lactams via post-Ugi-4CR/transamidation/cyclization in a one-pot, three-step sequence

• Amarendar Reddy Maddirala and
• Peter R. Andreana

Beilstein J. Org. Chem. 2018, 14, 875–883, doi:10.3762/bjoc.14.74

• spiro[indoline-3,2'-pyrrolidine]-2,5'-diones, via a post-Ugi-domino transamidation/cyclization sequential process, has been achieved in three sequential steps utilizing a one-pot reaction protocol. The variation in carboxylic acid substrates allows for the generation of new chiral racemic quaternary

• carbon centers under basic conditions providing molecular diversity and a small library of spirocyclic oxindoles. Keywords: convertible isocyanides; lactams; molecular diversity; oxindoles; transamidation; Introduction The Ugi-multicomponent coupling reaction [1][2], followed by post-modification

Enantioselective dioxytosylation of styrenes using lactate-based chiral hypervalent iodine(III)

• Morifumi Fujita,
• Koki Miura and
• Takashi Sugimura

Beilstein J. Org. Chem. 2018, 14, 659–663, doi:10.3762/bjoc.14.53

• substituted styrenes. The phenonium cation intermediate I4 contains two reaction sites on the ethylene bridge. Electron donation due to the lone pair on the oxygen atom of the internal tosyloxy group may weaken the bond between the tosyloxy-bonded carbon and the quaternary carbon in I4. The reaction of

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• -catalyzed trifluoromethylation of N-aryl acrylamides using Langlois’ reagent (CF3SO2Na) as a trifluoromethyl source and water as the reaction medium (Scheme 36). A variety of CF3-containing oxindoles bearing a quaternary carbon center were formed under this conditions. Furthermore, more CF3SO2Na (3.0 equiv

A Brønsted base-promoted diastereoselective dimerization of azlactones

• Danielle L. J. Pinheiro,
• Gabriel M. F. Batista,
• Pedro P. de Castro,
• Leonã S. Flores,
• Gustavo F. S. Andrade and
• Giovanni W. Amarante

Beilstein J. Org. Chem. 2017, 13, 2663–2670, doi:10.3762/bjoc.13.264

• analogue of streptopyrrolidine was accomplished in 65% overall yield. Keywords: azlactones; dimerization; diasteoreselective synthesis; kinetics; streptopyrrolidine analogue; Findings Azlactones have been acknowledged as a common nucleophilic reagent to introduce a quaternary carbon stereocenter in the α

Herpetopanone, a diterpene from Herpetosiphon aurantiacus discovered by isotope labeling

• Xinli Pan,
• Nicole Domin,
• Sebastian Schieferdecker,
• Hirokazu Kage,
• Martin Roth and
• Markus Nett

Beilstein J. Org. Chem. 2017, 13, 2458–2465, doi:10.3762/bjoc.13.242

• one occurred with a quaternary carbon (C-12). It was hence evident that the methyl group is attached to the hydroxy-substituted C-12, which itself is further connected with C-11 and C-14. HMBC interactions from H-15a and H-15b to C-12 lend additional support for the placement of the latter. The

• singlets in the 1H NMR spectrum. They were positioned next to the quaternary carbon C-2 on the basis of HMBC interactions. Interpretation of 2D NMR data allowed an extension of this residue with CH-4 and CH2-5. Ultimately, a heteronuclear long-range correlation from H-4 to C-6 linked the two fragments to

Iodoarene-catalyzed cyclizations of N-propargylamides and β-amidoketones: synthesis of 2-oxazolines

• Somaia Kamouka and
• Wesley J. Moran

Beilstein J. Org. Chem. 2017, 13, 1823–1827, doi:10.3762/bjoc.13.177

• tolerated. Alkylketone substrates were also successfully converted to 2-oxazolines. Installation of substituents on the tether led to facile formation of product 6m containing a quaternary carbon and compounds 6n and 6o but without any observed diastereoselectivity. Interestingly, the selectivity for 6o

A speedy route to sterically encumbered, benzene-fused derivatives of privileged, naturally occurring hexahydropyrrolo[1,2-b]isoquinoline

• Olga Bakulina,
• Alexander Ivanov,
• Vitalii Suslonov,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2017, 13, 1413–1424, doi:10.3762/bjoc.13.138

• hexahydropyrrolo[1,2-b]isoquinolone derivatives fused with benzene 10 that have pronounced three-dimensional features and potentially contain several quaternary carbon centers (Figure 2). The first aspect has been recently recognized [29] as a central principle in drug design ensuring effective interaction of

Switchable highly regioselective synthesis of 3,4-dihydroquinoxalin-2(1H)ones from o-phenylenediamines and aroylpyruvates

• Juraj Dobiaš,
• Marek Ondruš,
• Gabriela Addová and
• Andrej Boháč

Beilstein J. Org. Chem. 2017, 13, 1350–1360, doi:10.3762/bjoc.13.132

• , which showed an important four-bonded interaction between the hydrogen of the methylene C(3)=CH- group and the quaternary carbon C(4a) (Figure 2). The carbon C(4a) was interconnected in the HMBC with 2 other three-bonded interactions with hydrogen H-C(8) and H-C(6), whereas for the 16d (SYN) isomer the

Nucleophilic and electrophilic cyclization of N-alkyne-substituted pyrrole derivatives: Synthesis of pyrrolopyrazinone, pyrrolotriazinone, and pyrrolooxazinone moieties

• Işıl Yenice,
• Sinan Basceken and
• Metin Balci

Beilstein J. Org. Chem. 2017, 13, 825–834, doi:10.3762/bjoc.13.83

• broad singlet. The double bond proton in 12c resonating at 6.94 ppm as a singlet shows strong correlation in the HMBC spectrum with the quaternary carbon atoms resonating at 132.3, 130.8, and 123.1 as well as with the tertiary carbon atoms (=CH) at 118.6 ppm (Figure 4). This information clearly shows

• that the double bond (CH=C) is located between the pyrrole nitrogen atom and the benzene ring (Figure 4). On the other hand, the methylene protons in 13c resonating at 4.26 ppm as a singlet shows strong correlation with the quaternary carbon atoms resonating at 137.2 and 135.2 as well as with the

Synthesis of ribavirin 2’-Me-C-nucleoside analogues

• Fanny Cosson,
• Aline Faroux,
• Jean-Pierre Baltaze,
• Jonathan Farjon,
• Régis Guillot,
• Jacques Uziel and
• Nadège Lubin-Germain

Beilstein J. Org. Chem. 2017, 13, 755–761, doi:10.3762/bjoc.13.74

• , France Laboratoire CEISAM, UMR 6230, University of Nantes, 2 rue de la Houssinière, Nantes, France 10.3762/bjoc.13.74 Abstract An efficient synthetic pathway leading to two carbonated analogues of ribavirin is described. The key-steps in the synthesis of these ribosyltriazoles bearing a quaternary

• carbon atom in the 2’-position are an indium-mediated alkynylation and a 1,3-dipolar cyclization. Keywords: alkynylation; antiviral; cancer; C-nucleosides; ribavirin; Introduction The triazole nucleoside ribavirin (RBV, Figure 1) is used for the treatment of a number of viral infections and may be

Secondary metabolome and its defensive role in the aeolidoidean Phyllodesmium longicirrum, (Gastropoda, Heterobranchia, Nudibranchia)

• Alexander Bogdanov,
• Cora Hertzer,
• Stefan Kehraus,
• Samuel Nietzer,
• Sven Rohde,
• Peter J. Schupp,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2017, 13, 502–519, doi:10.3762/bjoc.13.50

• 1H,1H spin system required heteronuclear long range correlations for the elucidation of the remaining structural features and the closure of the cembrane ring. Methylene group CH2-3 exhibited HMBC correlations with resonances of the keto at C-2, sp2 quaternary carbon C-4 and tertiary carbon C-5 and

Methylenelactide: vinyl polymerization and spatial reactivity effects

• Judita Britner and
• Helmut Ritter

Beilstein J. Org. Chem. 2016, 12, 2378–2389, doi:10.3762/bjoc.12.232

• ); Introduction Methylenelactide (MLA) with the IUPAC name (6S)-3-methylene-6-methyl-1,4-dioxane-2,5-dione is a radically polymerizable vinyl-lactide derivative. The molecule’s quaternary carbon atom located at the double bond is substituted with an electron withdrawing (“pulling”) carbonyl group and an electron

• density of the vinyl protons than the electron-pushing substituent (Table S1, Figures S2 and S3, Supporting Information File 1). We further employed 13C NMR spectroscopy to provide a better view on the electron density of the double bond. It turned out that the quaternary carbon atoms of the double bond

New furoisocoumarins and isocoumarins from the mangrove endophytic fungus Aspergillus sp. 085242

• Ze’en Xiao,
• Senhua Chen,
• Runlin Cai,
• Shao’e Lin,
• Kui Hong and
• Zhigang She

Beilstein J. Org. Chem. 2016, 12, 2077–2085, doi:10.3762/bjoc.12.196

• , suggesting a molecular formula of C15H16O3. A careful comparison of its 1H and 13C NMR spectra (Table 1) with those of 2 indicated that compound 3 also shared the same isocoumarin skeleton as compound 2. The main differences were that an additional olefinic methine carbon at δC 99.6 and a quaternary carbon

Solvent-free synthesis of novel para-menthane-3,8-diol ester derivatives from citronellal using a polymer-supported scandium triflate catalyst

• Lubabalo Mafu,
• Ben Zeelie and
• Paul Watts

Beilstein J. Org. Chem. 2016, 12, 2046–2054, doi:10.3762/bjoc.12.193

• C0 = quaternary carbon. Gas chromatography (GC–MS) spectrometry was performed on a HP F5890 series LL plus gas chromatograph coupled to an HP 5972 series mass selective detector. The GC was equipped with a HP-5 MS capillary column (30 mm × 0.25 mm i.d.) and ultra-high purity helium (99.999%) carrier

Enantioconvergent catalysis

• Justin T. Mohr,
• Jared T. Moore and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2016, 12, 2038–2045, doi:10.3762/bjoc.12.192

• reaction was reported by Stoltz for the generation of enantioenriched all-carbon quaternary stereocenters from racemic allyl β-ketoesters (e.g., (±)-20 → (+)-23, Scheme 5) [29]. This particular reaction is especially unusual since the stereoablative step requires scission of a C–C bond at a quaternary

• carbon stereocenter to form achiral enolate intermediate 22. Since no kinetic resolution of the racemic starting material was observed, yields in excess of 90% with up to 92% ee could be obtained. In further studies, it was found that the putative enolate intermediate could also be trapped by a proton

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• ), their unique architecture is characterized by an ester-linked bromopyrrole carboxylic acid and a tetrahydropyrimidine ring in which one of the amino groups is attached to a quaternary carbon center. Due to their intriguing structures in combination with the promising biological properties this class of

Towards the total synthesis of keramaphidin B

• Pavol Jakubec,
• Alistair J. M. Farley and
• Darren J. Dixon

Beilstein J. Org. Chem. 2016, 12, 1096–1100, doi:10.3762/bjoc.12.104

• stereochemical configuration of the quaternary carbon was established by a diastereoselective Michael addition between a chiral, single enantiomer, cyclic β-amido ester and a nitroolefin, and, in the case of nakadomarin A the reaction could be rendered catalytic using a bifunctional cinchonine-derived urea

• hydroxypropyl chain attached to the quaternary stereocentre, poised for further functionalisation. Having established that the cinchonine-derived bifunctional Brønsted base/thiourea organocatalyst 12 was effective for installing two stereocentres including the quaternary carbon in a model system, we next