Harnessing enzyme plasticity for the synthesis of oxygenated sesquiterpenoids

• Melodi Demiray,
• David J. Miller and
• Rudolf K. Allemann

Beilstein J. Org. Chem. 2019, 15, 2184–2190, doi:10.3762/bjoc.15.215

• engineering; terpenes; Introduction Amorphadiene synthase (ADS) from Artemisia annua is a key enzyme involved in the biosynthesis of the antimalarial sesquiterpene drug artemisinin (1) [1][2][3][4]. ADS catalyses the Mg2+-dependent conversion of farnesyl diphosphate (FDP, 2) to amorpha-4,11-diene (3) with

• closure to form the bisabolyl cation (6). A [1,3]-hydride shift to form carbocation 7 and 1,10-ring closure yield the amorphyl cation (8). Finally, deprotonation generates amorpha-4,11-diene (3) [8][9]. Several sesquiterpene synthases including ADS accept FDP analogues containing a variety of heteroatoms

• : Mass spectra of 26 and 27. 1H NMR spectrum (400 MHz, CDCl3) of 12-methoxy-β-sesquiphellandrene (26) and 12-methoxyzingiberene (27) produced by ADS from 12-methoxy-FDP (12). Mechanism of the ADS-catalysed conversion of FDP (2) to amorpha-4,11-diene (3), a biosynthetic precursor of artemisinin (1

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

• reported as intermolecular cycloaddition reactions, there are some interesting reports regarding the intramolecular cycloaddition of fulvenes, summarised in Table 1. For the intramolecular cycloadditions of pentafulvenes, the fulvene has been reported to react as both diene and dienophile depending on the

• length of the extended pentafulvene chain, and the role of the fulvene in the reaction (diene or dienophile) [127]. In these examples, kigelinol and neoamphilectane are of great interest in biomimetic and natural product chemistry, as they exhibit antitrypanosomal [128][129] and antimalarial [130

• function as 2π, 4π, 6π or 10π components (Table 2). This functionality is dependent both on the other reactant partner, and the electronic effects of the fulvene substituents [96][97][98][99][153][156]. As an example, in [4 + 2] cycloadditions, fulvenes will participate as 4π components (diene), provided

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

• two new alkane derivatives colisiderin A and (7E,9E)-undeca-7,9-diene-2,4,5-triol [35] and from the organic extract of the red alga Laurencia obtusa [36]. However, to the best of our knowledge, ours is the first report of these brasilane-type sesquiterpenes obtained via biosynthetic genes. Metal ion

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• was isomerized in the presence of base and dehydrated to give diene 45. Reduction of 45 with 10% Pd/C afforded 8 in good yield (60%) after recrystallization. Benzylic oxidation of 8 (CrO3/HOAc, 45%), followed by C-14 ether cleavage (BBr3) and subsequent sodium borohydride reduction afforded 46 with

Analysis of sesquiterpene hydrocarbons in grape berry exocarp (Vitis vinifera L.) using in vivo-labeling and comprehensive two-dimensional gas chromatography–mass spectrometry (GC×GC–MS)

• Philipp P. Könen and
• Matthias Wüst

Beilstein J. Org. Chem. 2019, 15, 1945–1961, doi:10.3762/bjoc.15.190

• selina-3,7(11)-diene and γ-elemene via (E,E)-germacrene B are consistent with our results (Scheme 6) [9]. In Figure 9 the recorded mass spectra of d0-γ-elemene and d9-γ-elemene are shown as examples. Biosynthesis of guaiazulene, δ-elemene, guaia-6,9-diene and δ-selinene The formation of the aromatic

• described by Steele et al. for the formation of guaia-6,9-diene and δ-selinene via germacrene C could also be confirmed by feeding experiments (Scheme 7) [9]. Biosynthesis of (E)-β-caryophyllene and α-humulene The biosynthetic pathway postulated by Boland and Garms for the formation of (E)-β-caryophyllene

• A. *An incorporation of deuterium atoms into (+)-valencene could be detected, but due to coeluting substances no characteristic mass spectrum of d9-(+)-valencene could be obtained. Mechanistic rationale for the generation of the sesquiterpene hydrocarbons γ-elemene and selina-3,7(11)-diene via (E,E

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

•  2). This compound in reaction with AlCl3 without benzene afforded a mixture of allyl alcohol Z-9 and diene E-10a after aqueous work-up (Table 2, entries 1 and 2). The amount of 2.1 equivalents of AlCl3 is sufficient for activation of this transformation (compared to the amount of AlCl3 in entries 1

• and 2, Table 2). On the other hand, 1 equivalent of AlCl3 is not enough to activate allene 1a; thus, under these conditions, only acid 2 was obtained as a product of the hydrolysis of starting compound 1a (Table 2, entry 3). Methanolysis of the reaction mixture gave diene E-10b (Table 2, entry 7). The

• 1 equivalent of AlCl3 (see Table 2, entry 3). Addition of more than 1 equivalent of AlCl3 (2–5 equivalents) to a solution of 1a in CD2Cl2 in an NMR tube resulted in an immediate formation of diene E-14 as a part of a complex mixture (Scheme 8, see Supporting Information File 1 for NMR). Compare with

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

• system, where the corresponding diene 39 was isolated in up to 36% yield. In our earlier studies, typically approximately equimolar quantities of tartrate and alkylating agent were used, but with the halide now being synthetically more valuable, efforts focused on conditions which gave the best yields

• temperature before slow addition of the pre-cooled LDA minimised diene formation, with the excess residual unreacted tartrate being most conveniently removed by distillation on large-scale. Our second synthesis of DDSQ (2) introduced the full side-chain through alkylation with iodide 40 to give the alkylated

Catalytic asymmetric oxo-Diels–Alder reactions with chiral atropisomeric biphenyl diols

• Chi-Tung Yeung,
• Wesley Ting Kwok Chan,
• Wai-Sum Lo,
• Ga-Lai Law and
• Wing-Tak Wong

Beilstein J. Org. Chem. 2019, 15, 955–962, doi:10.3762/bjoc.15.92

• : asymmetric organocatalysis; axial chirality; biaryls; hydrogen bond; oxo-Diels–Alder reaction; Introduction The Diels–Alder (DA) reaction is a useful and easy-to-perform method for the synthesis of six-membered rings through the direct formation of C–C bonds between a diene and a dienophile (a substituted

• hydrogen bonding organocatalyst for the reaction between 1-dimethylamino-3-tert-butyldimethylsilyloxy-1,3-butadiene (Rawal’s diene) and aldehydes with excellent enantioselectivities (aromatic aldehyde: up to 86–98% ee) in 2003 [27]. Activation via a single-point hydrogen bond between one of the hydroxy

• form strong hydrogen bonds could perform the same catalytic role in oxo-DA reactions as reported in the literature. Inspired by Rawal’s work on TADDOL and BAMOL organocatalysts, we, in this work, have adopted a similar reaction of Rawal’s diene with benzaldehyde as a starting point of our study and

Hoveyda–Grubbs catalysts with an N→Ru coordinate bond in a six-membered ring. Synthesis of stable, industrially scalable, highly efficient ruthenium metathesis catalysts and 2-vinylbenzylamine ligands as their precursors

• Kirill B. Polyanskii,
• Kseniia A. Alekseeva,
• Pavel V. Raspertov,
• Pavel A. Kumandin,
• Eugeniya V. Nikitina,
• Atash V. Gurbanov and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2019, 15, 769–779, doi:10.3762/bjoc.15.73

• , ring-opening metathesis polymerization – ROMP and acyclic diene metathesis – ADMET. This motivates the investigations into the development of new, efficient, stable, and highly selective catalytic systems based on ruthenium complexes. However, in reality, a limited set of commercially available

Efficient synthesis of 4-substituted-ortho-phthalaldehyde analogues: toward the emergence of new building blocks

• Clémence Moitessier,
• Ahmad Rifai,
• Pierre-Edouard Danjou,
• Isabelle Mallard and
• Francine Cazier-Dennin

Beilstein J. Org. Chem. 2019, 15, 721–726, doi:10.3762/bjoc.15.67

• -methoxy-ortho-xylene in only 5% yield [14]. 4-HO-OPA was also described in 1997 by Taylor et al. as a crude product (via a Diels–Alder reaction of commercially available Danishefsky diene with 4,4-diethoxybut-2-ynal) for the synthesis of an antitumor analogue [15]. This aforementioned strategy was applied

Dirhodium(II)-catalyzed [3 + 2] cycloaddition of N-arylaminocyclopropane with alkyne derivatives

• Wentong Liu,
• Yi Kuang,
• Zhifan Wang,
• Jin Zhu and
• Yuanhua Wang

Beilstein J. Org. Chem. 2019, 15, 542–550, doi:10.3762/bjoc.15.48

• due to cycloaddition with an olefin group in 2j (Table 3, entry 9). When 2k was applied in the reaction, the addition product was obtained with a yield of 44% with the alkyne group being involved in the reaction (Table 3, entry 10). The reaction with 2l mainly produced 1,3-diene product 4l with a

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• tags. c) PEG-tethered catalysts. Chemical structure and components of amphiphilic molecule PTS and derivatives. In vivo metathesis with an artificial metalloenzyme based on the biotin–streptavidin technology. Most common metathesis reactions. Ring-opening metathesis polymerization (ROMP), acyclic diene

Application of olefin metathesis in the synthesis of functionalized polyhedral oligomeric silsesquioxanes (POSS) and POSS-containing polymeric materials

• Patrycja Żak and
• Cezary Pietraszuk

Beilstein J. Org. Chem. 2019, 15, 310–332, doi:10.3762/bjoc.15.28

• silsesquioxanes (POSS) and POSS-containing polymeric materials. Three types of processes, i.e., cross metathesis (CM) of vinyl-substituted POSS with terminal olefins, acyclic diene metathesis (ADMET) copolymerization of divinyl-substituted POSS with α,ω-dienes and ring-opening metathesis polymerization (ROMP) of

• metathesis in chemistry of unsaturated derivatives of POSS is limited to three types of processes, i.e., cross metathesis (CM) of vinyl-substituted POSS with terminal olefins, acyclic diene metathesis (ADMET) copolymerization of divinyl-substituted POSS with α,ω-dienes and ring-opening metathesis

• catalyst permits selective CM. Another metathetic transformation – acyclic diene metathesis copolymerization – permits introduction of a POSS group to the copolymer main chain. This methodology has not been thoroughly studied so far. In turn, ring-opening metathesis (co)polymerization is a convenient tool

Synthesis of 1,2-divinylcyclopropanes by metal-catalyzed cyclopropanation of 1,3-dienes with cyclopropenes as vinyl carbene precursors

• Jesús González,
• Alba de la Fuente,
• María J. González,
• Laura Díez de Tejada,
• Luis A. López and
• Rubén Vicente

Beilstein J. Org. Chem. 2019, 15, 285–290, doi:10.3762/bjoc.15.25

• proceeded in reasonable yields while the diastereoselectivity strongly depends on the structure of the diene. An example of an intramolecular process as well as the use of furan and 1,4-cyclohexadiene as dienes are also reported. Keywords: cyclopropanation; cyclopropenes; dienes; divinylcyclopropanes

• substituted alkene, allowing the synthesis of 1,2-divinylcyclopropane 3k within the typical range of yields and cis/trans selectivities. Finally, 1,2,3-trisubstituted divinylcyclopropane 3l was prepared in 50% (cis/trans = 2.5:1) from cyclopropene 1a and (1E,3E)-1,4-diphenylbuta-1,3-diene through a

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• -derived precursors When Garner’s aldehyde (R)-5 prepared from D-serine was subjected to ZnCl2-catalyzed cyclocondensation with Danishefsky's diene a (>9:1) mixture of diastereoisomeric pyranones 6 was formed with the threo isomer 6a prevailing. Oxidative removal of two carbon atoms was followed by formate

Olefin metathesis in multiblock copolymer synthesis

• Maria L. Gringolts,
• Yulia I. Denisova,
• Eugene Sh. Finkelshtein and
• Yaroslav V. Kudryavtsev

Beilstein J. Org. Chem. 2019, 15, 218–235, doi:10.3762/bjoc.15.21

• -telechelic poly(1,4-butadiene) bearing alkoxyamine termini was obtained by ROMP of trans,trans,cis-1,5,9-cyclododecatriene in the presence of a symmetric acyclic olefin CTA (Scheme 2). This telechelic polybutadiene was used as the macroinitiator for the NMP of styrene and diene monomers to yield unimodal SBS

• multiple click reactions of the diazido-telechelic PBD with a dialkynyl-containing azobenzene chromophore. The newly formed triazole moieties can tune and improve the photoresponsive properties of PBD. α,ω-Functional telechelic polymers also can be synthesized by acyclic diene metathesis (ADMET

Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

• Pierre-Antoine Nocquet,
• Aurélie Macé,
• Frédéric Legros,
• Jacques Lebreton,
• Gilles Dujardin,
• Sylvain Collet,
• Arnaud Martel,
• Bertrand Carboni and
• François Carreaux

Beilstein J. Org. Chem. 2018, 14, 2949–2955, doi:10.3762/bjoc.14.274

• the syn diastereomer 18 in high stereoselectivity (93:7). After silylation of the free hydroxy group, the cleavage of the PMB ether with DDQ led to alcohol 20 in 77% yield for the two steps. Ring-closing metathesis of diene 21, obtained by O-vinylation of 20, gave the dihydropyran 22 in 53% overall

Domino ring-opening–ring-closing enyne metathesis vs enyne metathesis of norbornene derivatives with alkynyl side chains. Construction of condensed polycarbocycles

• Ritabrata Datta and
• Subrata Ghosh

Beilstein J. Org. Chem. 2018, 14, 2708–2714, doi:10.3762/bjoc.14.248

• functional group and the substrate structure and may follow a different reaction course than what is usually observed. In cases where ROM–RCEYM occurred, the resulting 1,3-diene reacts in situ with the dienophile to provide condensed tetracyclic systems. Keywords: Diels–Alder reaction; domino process; enyne

• derivative 2 would provide the tricyclic 1,3-diene 3 which on Diels–Alder reaction with a dienophile would enable access to condensed polycyclic structures 4 (Scheme 2). Thus an appropriately chosen norbornene derivative and a dienophile may provide the B/C/D/E ring system of retigeranic acids. Herein we

• diene. Thus unlike metathesis of 7a, metathesis of its acetate analogue 7b occurred through a domino ROM–RCEYM process. Addition of the Ru-carbene 10 arising from ring opening of norbornene unit in 7b could add to the acetylenic unit of another molecule of 7b leading to copolymerization. However, this

Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• substrates 11g and 11h containing ester and ketone moieties, respectively, which are generally more reactive toward nucleophiles than CO2. Notably, the Co-catalyst system was found to be applicable for the carboxylation of 1,3-diene derivatives 14 with CO2 (Scheme 12), which afforded various hexa-3,5-dienoic

• acid derivatives. Diene 14a was converted into the corresponding carboxylic acid 15a in good yield. In addition, 1,4-dienes having cyclohexenyl and geminal diphenyl substituents (14b and 14c) produced their corresponding linear carboxylic acids 15b and 15c in 78% and 57% yields, respectively. Substrate

• -catalyzed carboxylation of 11a. Scope of the carboxylation of allylarenes 11. Scope of the carboxylation of 1,4-diene derivatives 14. Plausible reaction mechanism for the Co-catalyzed C(sp3)–H carboxylation of allylarenes. Optimization of the Co-catalyzed carboxyzincation of 16a. Derivatization of the

Cobalt-catalyzed nucleophilic addition of the allylic C(sp³)–H bond of simple alkenes to ketones

• Tsuyoshi Mita,
• Masashi Uchiyama,
• Kenichi Michigami and
• Yoshihiro Sato

Beilstein J. Org. Chem. 2018, 14, 2012–2017, doi:10.3762/bjoc.14.176

• species (Figure 1). However, the substrates employed have been restricted to allylarenes and 1,4-enyne, and 1,4-diene derivatives and α-olefins were totally unexplored. Therefore, the next challenge would be to use less reactive α-olefins (pKa value of 1-propene = 43). In this paper, we describe an

Synthesis of pyrimido[1,6-a]quinoxalines via intermolecular trapping of thermally generated acyl(quinoxalin-2-yl)ketenes by Schiff bases

• Svetlana O. Kasatkina,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev,
• Ivan G. Mokrushin and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2018, 14, 1734–1742, doi:10.3762/bjoc.14.147

• results in the formation of a peculiar system of conjugated double bonds, which can potentially act as either oxo-diene or aza-diene (Figure 3). To the best of our knowledge, there is no example of the involvement of the aza-diene fragment of acyl(quinoxalin-2-yl)ketenes into intermolecular trapping by

• ]quinoxaline-1,2,4(5H)-triones III [23][56] (Scheme 1). According to the literature data, precursors I and II are unsuitable for achieving the proposed goal as the generated ketene IV reacts only at its oxo-diene fragment in intermolecular trapping reactions with various dienophiles [57][58][59][60][61][62

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• , the PMB-protected epoxide 121 was converted to diene 122. The dihydropyran ring of 123 was constructed by RCM of 122 catalyzed by a Grubbs 1st generation catalyst. The isomerization of the double bond in 123 by treatment with a Wilkinson catalyst under basic conditions afforded glycal 124 (Scheme 16

Lanyamycin, a macrolide antibiotic from Sorangium cellulosum, strain Soce 481 (Myxobacteria)

• Lucky S. Mulwa,
• Rolf Jansen,
• Dimas F. Praditya,
• Kathrin I. Mohr,
• Patrick W. Okanya,
• Joachim Wink,
• Eike Steinmann and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 1554–1562, doi:10.3762/bjoc.14.132

• . The only remaining NH group finally filled the gap between the amide C-27 (δC 171 ppm) and C-26 (δC 75 ppm) based on the HMBC correlation H-26/C-27 thus forming the unusual and unstable N-acyl hemiaminal that explains the interconversion of lanyamycin isomers 1 and 2. The E configuration of the diene

• double bonds Δ10,11 and Δ12,13 was recognized from their large coupling constants of about 15 Hz while 1H,1H-ROESY correlations between H-3 and H-5 as well as between methyl-37 and both methyl-38 and methoxy-36 suggested the E configuration of the substituted Δ2,3,Δ4,5-diene. Likewise, the E

• difference is the missing methyl group of the unsubstituted diene in 1/2. Further comparison of the NMR data revealed a significant lower 13C-shift of C-7 of about 5–6 ppm. Together with the missing vicinal coupling between H-7 and H-8 this indicated an inverted configuration of the secondary alcohol at C-7

Three-component coupling of aryl iodides, allenes, and aldehydes catalyzed by a Co/Cr-hybrid catalyst

• Kimihiro Komeyama,
• Shunsuke Sakiyama,
• Kento Iwashita,
• Itaru Osaka and
• Ken Takaki

Beilstein J. Org. Chem. 2018, 14, 1413–1420, doi:10.3762/bjoc.14.118

• coupling reaction between iodobenzene (1a), 5-phenylpenta-1,2-diene (2a), and 4-methylbenzaldehyde (3a) in the presence of CoBr2 (10 mol %), CrCl3 (20 mol %), and manganese powder (2.0 equiv), using trimethylsilyl chloride (TMSCl, 1.2 equiv) as a trapping reagent [7]. These results are summarized in Table

• good yields (Scheme 8). During the investigation of allenes, it was observed that, when oxygen substituents were present at the allenyl position, coupling products with reversed diastereoselectivity were obtained (Scheme 9). Thus, treatment of 4-benzyloxybuta-1,2-diene (5) with 1 and 3a under identical

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• methyl ester 120 in four steps (Scheme 39) [73]. The organocatalytic properties of this inherently chiral calixarene Brønsted acid was firstly examined in the aza-Diels–Alder reaction of imines bearing electron-withdrawing or electron-donating substituents 122 with Danishefsky’s diene (123, Scheme 40