Remarkable functions of sn-3 hydroxy and phosphocholine groups in 1,2-diacyl-sn-glycerolipids to induce clockwise (+)-helicity around the 1,2-diacyl moiety: Evidence from conformation analysis by ¹H NMR spectroscopy

• Yoshihiro Nishida,
• Mengfei Yuan,
• Kazuo Fukuda,
• Kaito Fujisawa,
• Hirofumi Dohi and
• Hirotaka Uzawa

Beilstein J. Org. Chem. 2017, 13, 1999–2009, doi:10.3762/bjoc.13.196

• the 1H NMR spectra in Figure 2, a part of 3 is isomerized to 1,3-isomer during storage in solutions. To examine the possible effects from this isomer, the isomerization is promoted up to 50%, and the 1H NMR spectrum of the isomeric mixture is analyzed. This experiment indicates that the presence of

• conformational equilibrium among three staggered conformers, namely gt(+), gg(−) and tg around the 1,2-diacyl moiety. 1H NMR spectra of 1,2-dipalmitin (3) in CDCl3 after partial isomerization into the 1,3-isomer. (a) The expanded spectrum of 3 in CDCl3, (b) 3 in a mixed solvent with ca. 10% methanol-d4 in CDCl3

Are boat transition states likely to occur in Cope rearrangements? A DFT study of the biogenesis of germacranes

• José Enrique Barquera-Lozada and
• Gabriel Cuevas

Beilstein J. Org. Chem. 2017, 13, 1969–1976, doi:10.3762/bjoc.13.192

• [64]. The stability of the wave functions of all the transition states was checked. An unrestricted wave function was used to calculate the activation energy of the cis/trans isomerization of the (Z,E)-germacranolide. All energies were reported with zero-point energy corrections and all TS geometries

• the Cope rearrangement can proceed, the (Z,E)-germacranolide 1, must isomerize to the corresponding (E,E)-germacranolide 4. This process is highly unfavorable, its energetic barrier is about 55.7 kcal/mol, which is very close to the reported activation energies for the ethylene thermal isomerization

• (≈65 kcal/mol) [65][66][67][68]. Therefore, this high energy TS makes path N and path P unlikely. It is important to point out that in nature this isomerization of germacranes can be catalyzed by different mechanism. For example, other cis/trans transformations have been biomimetically catalyzed by

Synthesis of benzothiophene and indole derivatives through metal-free propargyl–allene rearrangement and allyl migration

• Jinzhong Yao,
• Yajie Xie,
• Lianpeng Zhang,
• Yujin Li and
• Hongwei Zhou

Beilstein J. Org. Chem. 2017, 13, 1866–1870, doi:10.3762/bjoc.13.181

• unstable or reactive polyfunctionalized allene substrates [17][18][19][20][21][22][23][24][25][26][27]. Although transition metal (e.g., Au, Pd)-catalysed propargyl–allenyl isomerization and cyclization reactions have been established [28][29], such transformations promoted by a base to construct

NHC-catalyzed cleavage of vicinal diketones and triketones followed by insertion of enones and ynones

• Ken Takaki,
• Makoto Hino,
• Akira Ohno,
• Kimihiro Komeyama,
• Hiroto Yoshida and
• Hiroshi Fukuoka

Beilstein J. Org. Chem. 2017, 13, 1816–1822, doi:10.3762/bjoc.13.176

• should be delivered to the ynones 2 from the same side to yield E-products 4 exclusively. However, 4 were obtained as a mixture of E- and Z-isomer in the most cases. Since pure Z-isomer of the product 4ai was exceptionally isolated, its isomerization was tested in order to explain the stereochemistry

• salts. ORTEP drawing of Z-4ai. ORTEP drawing of 10. Reaction process. Reaction mechanism. Isomerization of the stereochemistry of 4ai. Reaction of cycloalkane-1,2-diones with phenyl vinyl ketone (6a). Preparation and reactivity of the bisacylated Breslow intermediate 10. Preparation of the iminium salt

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Base-promoted isomerization of CF₃-containing allylic alcohols to the corresponding saturated ketones under metal-free conditions

• Yoko Hamada,
• Tomoko Kawasaki-Takasuka and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2017, 13, 1507–1512, doi:10.3762/bjoc.13.149

• We have previously reported [1][2][3] an extremely efficient isomerization process of γ-trifluoromethylated propargylic alcohols 1F to the corresponding α,β-unsaturated ketones (E)-5 by the action of a weak base like Et3N under THF reflux conditions (Scheme 1). From the mechanistic point of view

• equally) preferable to 4F-Ob. This result allowed us to similarly anticipate the successful isomerization of CF3-containing allylic alcohols 2F to the corresponding saturated ketones 7 when the substrates possessed appropriate aromatic substituents as R. With reference to these computational results, we

• decided to employ the CF3-containing allylic alcohols (E)-6 at the γ-position as substrates for the amine-promoted isomerization, instead of the corresponding propargylic alcohols 1F. Although a similar Ru- [8][9][10][11][12] or Fe-catalyzed processes [13] have been previously demonstrated, our present

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

• formed as a 0.8:1 mixture of anti/syn diastereomers (Table 1). However, it was promptly noted that this mixture converges to thermodynamically more stable anti-10e (the isomerization occurs on heating to 80 °C or, more slowly, even at room temperature). Esterification of anti/syn-10e in the presence of

• potassium carbonate led to the formation of anti-10e' as a sole product, presumably, via a base-promoted enolization and subsequent isomerization of the syn-10e (10e', Scheme 2). Enolization is thought to be a key event in the formation of the CCR products which can occur via two alternative mechanisms: (a

• group between syn- and anti-diastereomers of 11a-Me in compounds 10h–k, 10m,n. Criteria for stereochemistry assignment of anti-10o. Formation of unwanted products 11 and 12 in lieu of the CCR with 9p–t. Syn/anti isomerization of compound 10e. Alternative mechanistic pathways for the CCR. Formation and

An improved preparation of phorbol from croton oil

• Alberto Pagani,
• Simone Gaeta,
• Andrei I. Savchenko,
• Craig M. Williams and
• Giovanni Appendino

Beilstein J. Org. Chem. 2017, 13, 1361–1367, doi:10.3762/bjoc.13.133

• cancer prevention and treatment remains high [13]. Phorbol occurs in croton oil as a mixture of di- and triesters, generally in a ca. 1:2 ratio [6], and therefore isolation involves a deacylation step, critical because of the sensitivity of phorbol to isomerization to 4α-phorbol (2) by a base-induced

Total synthesis of elansolids B1 and B2

• Liang-Liang Wang and
• Andreas Kirschning

Beilstein J. Org. Chem. 2017, 13, 1280–1287, doi:10.3762/bjoc.13.124

• functionalized alkene 14 which is suited for a sequential cross-coupling strategy (Scheme 2). Under the catalytic conditions, we did not encounter isomerization of the alkene and diene configurations in vinyl boronate 13. The preparation of the newly modified western fragment started from known IMDA product 9 [7

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• saccharides. The interest in hexofuranoses is based on the arabinogalactan-rich membrane of Mycobacterium tuberculosis and other harmful microorganisms which consists of primarily Araf and Galf subunits [44]. One key step in the biosynthesis of these hexofuranoses is the isomerization of uridine 5′-diphospho

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• three dimensional conformation of the archazolids by NMR methods, molecular modelling and chemical derivatizations [59][60]. During these studies, they became aware that C2–C5 diene of acyclic analogs would be very labile towards isomerization. However, such processes would be suppressed in the

• any traces of water which were shown to lead to unfavourable isomerization pathways. Finally, an oxazaborolidine-assisted borane reduction [78] set the stereogenic center at C15 and global deprotection gave synthetic archazolid A, which proved to be fully identical with a natural sample, thus

• to synthesize archazolid B (2) in only 19 steps from (S)-Roche ester 41 (longest linear sequence). O'Neil’s retrosynthetic analysis and strategy As discussed above one of the main difficulties of any archazolid synthesis involves the labile C1 to C5-dienoate system, which is prone to isomerization

Cycloheximide congeners produced by Streptomyces sp. SC0581 and photoinduced interconversion between (E)- and (Z)-2,3-dehydroanhydrocycloheximides

• Li Yang,
• Ping Wu,
• Jinghua Xue,
• Huitong Tan,
• Zheng Zhang and
• Xiaoyi Wei

Beilstein J. Org. Chem. 2017, 13, 1039–1049, doi:10.3762/bjoc.13.103

• intensities) at 36 h (Figure 5), whereas no changes were detected for the solutions kept in the dark (Figure 5), confirming the interconversion is a photoinduced geometrical isomerization. Compounds 2 and 3 possess a chiral 6-ethylidene-2-cyclohexenone chromophore. To the best of our knowledge, Z/E

• Φ of these geometries are presented in Table 2. Compound 4 has a structure similar to 2 except for replacement of the C2–C3 double bond by a single bond. Its geometrical isomerization was not observed in the present study, but (E)-2-ethylidenecyclohexanone, which has a similar chromophore to that of

• of C6–Cα bond (Table 2). In respect to the photoreaction path, it is predicted that the Z/E isomerization of 2a/3a is impossible to take place along the S1 surface due to the presence of large rotational barrier (>25 kcal/mol) in accessing the twisted intermediates (Figure 6). Instead, radiationless

A strategic approach to [6,6]-bicyclic lactones: application towards the CD fragment of DHβE

• Tue Heesgaard Jepsen,
• Emil Glibstrup,
• François Crestey,
• Anders A. Jensen and
• Jesper Langgaard Kristensen

Beilstein J. Org. Chem. 2017, 13, 988–994, doi:10.3762/bjoc.13.98

• % isolated yield with only 13% formation of the elimination product 22, and no trace of the undesired (Z)-6-exo product. The subsequent hydrolysis of the ethyl ester 24 at room temperature smoothly provided carboxylic acid 25 in 81% yield with retention of the E-configuration, whereas isomerization of the

Total synthesis of TMG-chitotriomycin based on an automated electrochemical assembly of a disaccharide building block

• Yuta Isoda,
• Norihiko Sasaki,
• Kei Kitamura,
• Shuji Takahashi,
• Sujit Manmode,
• Naoko Takeda-Okuda,
• Jun-ichi Tamura,
• Toshiki Nokami and
• Toshiyuki Itoh

Beilstein J. Org. Chem. 2017, 13, 919–924, doi:10.3762/bjoc.13.93

• chemical species [28][29]. Taking the stability of the glycosyl triflate α-isomer 3aα into consideration, we propose a reaction mechanism involving α/β isomerization of glycosyl triflate 3a as shown in Figure 2. The more reactive β-isomer 3aβ might give the disaccharide α-isomer 5aα exclusively if there is

• an equilibrium between the α-isomer and the β-isomer of 3a. To the contrary, glycosyl triflate 3b, derived from thioglycoside 2b, might be more reactive and affords the β-product 5bβ before isomerization from the α-isomer 3bα to the β-isomer 3bβ. In this case, glycosylation via 3bα becomes the major

Continuous-flow processes for the catalytic partial hydrogenation reaction of alkynes

• Carmen Moreno-Marrodan,
• Francesca Liguori and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2017, 13, 734–754, doi:10.3762/bjoc.13.73

• issues owing to many potential side reactions, particularly in relation to chemoselectivity, i.e., over-hydrogenation of alkenes to alkanes [44][45], resistance of other functional groups (ketones [46][47], amines [48][49], azides [50]), regioselectivity [51][52] , isomerization [53][54] and

• . Selectivity in partial hydrogenation is ruled by the relative rates of the first and second hydrogenation steps, as well as by the adsorption strengths of alkyne and alkene over the metal catalyst surface. Other side-products may include those due to dimerization and isomerization reactions, depending on the

N-Propargylamines: versatile building blocks in the construction of thiazole cores

• S. Arshadi,
• E. Vessally,
• L. Edjlali,
• R. Hosseinzadeh-Khanmiri and
• E. Ghorbani-Kalhor

Beilstein J. Org. Chem. 2017, 13, 625–638, doi:10.3762/bjoc.13.61

• proposed by Balova et al. In their approach, a sequential cyclocondensation/5-exo-dig cyclization process between 2-amino-N-propargylanilines 4 and CS2 afforded heterocyclic systems of type 5. Isomerization of the latter compounds upon heating in the presence of KOH in ethanol gave the corresponding 2

• ) electrophilic addition of I2 to the alkyne moiety of this intermediate produces the iodonium intermediate B, (iii) isomerization of iodonium B gives intermediate C and (iv) a sequential intramolecular cyclization and HI elimination of C finally affords thiazolidines 27 [88]. Seeking for a greener approach

• the intermediate C. Finally, the isomerization of C affords the observed products 49 (Scheme 14) [96]. In 2011, X. Meng and S. Kim reported an example of thiazolidine preparation through a Mo-catalyzed 5-exo-dig cyclization of the N-propargylthiocarbamate 50 in toluene under irradiation at 350 nm. As

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• sustainable base [43][44]. The concept of flash chemistry has been successfully employed for outpacing fast isomerization reactions. The accurate control of the residence time, realized in a microreactor, could suppress or avoid isomerization of unstable intermediates. This is often unavoidable when the same

• reactions are run in batch mode [45][46][47]. Yoshida and Kim recently provided an astonishing example on the potential of flash chemistry in controlling fast isomerization of organolithiums [48]. The authors designed a chip microreactor (CMR), able to deliver a reaction time in the range of submilliseconds

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• with alkynes 94, followed by intramolecular nucleophilic vinylpalladation to give indenol derivatives 95 [54]. Further heating of 95 led to isomerization of the double bond to give the corresponding 1-indanones 96 (Scheme 30). 3-Hydroxy-1-indanones 99a–j have been applied in the synthesis of human

• % enantiomeric excess (Scheme 33). 2-Methylbenzil (108) has been converted to 2-hydroxy-2-phenylindan-1-one (109) as a result of photochemical isomerization, in 90% yield (Scheme 34) [59]. Wagner et al. have reported that hexaisopropyl-, hexaethyl- and hexamethylbenzils 110a–c photocyclized to the corresponding

• -indanones 159a–g by a rhodium-catalyzed isomerization of racemic α-arylpropargyl alcohols 158 has been developed by Shintani, Okamoto and Hayashi (Scheme 46) [76]. By the mechanistic investigations using deuterium-labeled substrates, the authors have disclosed that the methine proton of the alcohol goes to

Decarboxylative and dehydrative coupling of dienoic acids and pentadienyl alcohols to form 1,3,6,8-tetraenes

• Ghina’a I. Abu Deiab,
• Mohammed H. Al-Huniti,
• I. F. Dempsey Hyatt,
• Emma E. Nagy,
• Kristen E. Gettys,
• Sommayah S. Sayed,
• Christine M. Joliat,
• Paige E. Daniel,
• Rupa M. Vummalaneni,
• Andrew T. Morehead Jr,
• Andrew L. Sargent and
• Mitchell P. Croatt

Beilstein J. Org. Chem. 2017, 13, 384–392, doi:10.3762/bjoc.13.41

• quantitative isomerization of the bis-allylic group into a linear pentadienyl system. Increasing the reaction time did not result in greater conversion to tetraene 8a, which indicates that the products may be competitively ligating and poisoning the Pd(0) catalyst (see Supporting Information File 1 for

• additional evidence of product inhibition). The isomerization reaction to form 22 was presumably occurring via ionization of the allylic system using Pd(0), followed by recombination of the carboxylate at the terminal position of the pentadienyl system. Based on these data, we hypothesized that a two

• -component reaction using a dienoic acid and bis-allylic acetate might be possible, however, the presence of both water and a carboxylic acid would increase the possibility for isomerization of the 1,3,6,8-tetraenes into the fully conjugated 1,3,5,7-tetraenes, or possibly polymerization. Despite the low

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

• double bonds [105]. In any case, the obtained data failed to shed light on the origin of this cis double bond in the final rifamycin structure, although clearly it arises from isomerization of an initially formed trans alkene. Indeed, further studies on the Rif PKS and a handful of other systems have

• revealed that at least a subset of cis double bonds in the products arise from mechanisms other than direct DH-catalyzed dehydration. These include isomerization by either integral enoyl isomerase domains (present in trans-AT PKSs only) [21][22][106] or by post-PKS domains [107][108][109], and TE-mediated

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• second part of their work, they developed adequate conditions to carry out the decyanation reaction without olefin isomerization [18]. They explored several methods for the preparation of 12-butyltricosa-1,22-diene 3 (R = n-C4H9). The reaction was carried out in a slurry of K/Al2O3 in hexane, hexane

• /toluene (1:1) and toluene giving 20%, 63% and 75% of olefin isomerization (from NMR and GC), respectively, for each solvent [34]. This isomerization was attributed to the translocation of the tertiary radical intermediate to a more stable allyl radical leading to the double bond migration. This

• rearrangement was avoided using K/Ph3CH in hexane/ether (3 R = n-C4H9, 41% yield) or K/HMPA/t-BuOH in ether (3 R = n-C4H9, 99% yield). The latter optimized conditions allow the decyanation of alkylcyano α,ω-dienes 2 in quantitative yields with no detection of olefin isomerization (Scheme 3). Radical

Diels–Alder reactions of myrcene using intensified continuous-flow reactors

• Christian H. Hornung,
• Miguel Á. Álvarez-Diéguez,
• Thomas M. Kohl and
• John Tsanaktsidis

Beilstein J. Org. Chem. 2017, 13, 120–126, doi:10.3762/bjoc.13.15

• thermal isomerization at temperatures between 400 and 600 °C. This was first described by Goldblatt and Palkin in 1947 [11]. Myrcene is a very versatile molecule that can act as the starting material for several valuable compounds. The industrial production of a series of top-selling flavors and

Benzothiadiazole oligoene fatty acids: fluorescent dyes with large Stokes shifts

• Lukas J. Patalag and
• Daniel B. Werz

Beilstein J. Org. Chem. 2016, 12, 2739–2747, doi:10.3762/bjoc.12.270

• isomerization are presented. The absorption properties are modulated by the number of conjugated C=C double bonds of the oligoene chain ranging from one to three. Large Stokes shifts of about 4900–5700 cm−1 and fluorescence quantum yields of up to 0.44 were observed. Keywords: fatty acid; fluorescence; lipid

• isomerization has to take place. To access the benzothiadiazole (BTD) fatty acid 3 with just one conjugated double bond we made use of the Wittig reaction starting with commercially available aldehyde 1. As expected, the (Z)-isomer was the major product; thus, we performed a subsequent cis–trans isomerization

• with traces of iodine as catalyst (Scheme 1). It proved to be crucial to employ degassed hexane and to ensure a strict exclusion of oxygen. Considering both, the isomerization was finished just by removing the solvent while the yield of compound 3 was not hampered. For a BTD fatty acid analogue of the

Identification, synthesis and mass spectrometry of a macrolide from the African reed frog Hyperolius cinnamomeoventris

• Markus Menke,
• Pardha Saradhi Peram,
• Iris Starnberger,
• Walter Hödl,
• Gregory F.M. Jongsma,
• David C. Blackburn,
• Mark-Oliver Rödel,
• Miguel Vences and
• Stefan Schulz

Beilstein J. Org. Chem. 2016, 12, 2731–2738, doi:10.3762/bjoc.12.269

• , followed by esterification with 9-decenoic acid (8) using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and 4-(dimethylamino)pyridine (DMAP) [24][25]. The following RCM was performed using Grubbs–Hoveyda II catalyst (11) and hexafluorobenzene as an additive [26]. During the reaction isomerization

• -trimethylphenyl)-2-imidazolidinylidene)dichloro(phenylmethylene)(tricyclohexylphosphine)ruthenium reduced the isomerization, leading to an (E/Z)-mixture of 2. Finally, the (Z)-selective Grubbs catalyst 12 furnished the best results [29][30]. This catalyst yielded only the desired product (R)-2 with a (Z

• material. After copper-catalyzed opening of the epoxide with 6-heptenylmagnesium bromide obtained from 7-bromo-1-heptene (14) and Steglich esterification with 5-hexenoic acid (16), RCM using (Z)-selective Grubbs catalyst 12 was used to synthesize macrolide (R)-1 without any isomerization. Comparison of the

Formose reaction controlled by boronic acid compounds

• Toru Imai,
• Tomohiro Michitaka and
• Akihito Hashidzume

Beilstein J. Org. Chem. 2016, 12, 2668–2672, doi:10.3762/bjoc.12.263

• formose reaction consists of several elemental reaction steps, e.g., acyloin condensation, aldol reaction, retro-aldol reaction, aldose–ketose isomerization, and Cannizzaro reaction, and the product, formose, is a complicated mixture of more than thirty species of sugars and sugar alcohols including non