Fluorination of some highly functionalized cycloalkanes: chemoselectivity and substrate dependence

• Attila Márió Remete,
• Melinda Nonn,
• Santos Fustero,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2017, 13, 2364–2371, doi:10.3762/bjoc.13.233

• dependence, neighboring group assistance and chemodifferentiation. Keywords: amino acids; chemoselectivity; fluorine; functionalization; stereoisomers; Introduction Fluorinated molecules exert an ever-increasing impact in medicinal chemistry thanks to their valuable biological properties. Numerous drugs

• -membered diol stereoisomers (±)-1 and (±)-4 proved to be highly substrate dependent and on the basis of our earlier findings on substrate determinant fluorinations [37], we next investigated the effect of the nature of the N-protecting group on this reaction. The treatment of N-Cbz-protected dihydroxylated

Synthesis of ergostane-type brassinosteroids with modifications in ring A

• Vladimir N. Zhabinskii,
• Darya A. Osiyuk,
• Yuri V. Ermolovich,
• Natalia M. Chaschina,
• Tatsiana S. Dalidovich,
• Miroslav Strnad and
• Vladimir A. Khripach

Beilstein J. Org. Chem. 2017, 13, 2326–2331, doi:10.3762/bjoc.13.229

• revealed the existence of all possible configurations of vicinal hydroxy groups among the 2,3-stereoisomers of castasterone [20]. Minor BS constituents with structural fragments of types 6–8 (Scheme 1) showed reduced growth promoting biological activity when compared to castasterone, thus indicating that

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• tetracyanoethylene (TCNE) with numerous applications [1][2][3], and its role in cycloaddition reactions is of special interest. Dialkyl dicyanofumarates E-1 and dicyanomaleates Z-1 ((E)- and (Z)-butenedioates 1, Figure 1) are less known, but the availability of both stereoisomers is of great advantage for the

• reagent yielded 1-azabicyclo[2.1.1]hexanes 60 as products of an intramolecular cyclization of the intermediate zwitterion 57. In all cases, these products were obtained as mixtures of cis-and trans-stereoisomers in favor of the trans-isomer [59][61]. Another class of nucleophilic reagents used for

• as single stereoisomers (79% yield) [63]. The same reaction pathway was observed in reactions with aromatic 1,2-diamines. For example, starting with benzene-1,2-diamine, the corresponding 2-oxo-1,2,3,4-tetrahydroquinoxaline derivatives, analogous to 73, were obtained in high yields as Z-isomers

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• corresponding adduct 44 in 93% yield. Importantly, both stereoisomers obtained were oxime E,Z-isomers with the C-7 relative configuration being the same as in myrioneurinol. Subsequent deoxygenation and reduction of aldoxime followed by transformation of the malonate unit to the formyl group furnished

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

• chirality transmission (CT) on the basis of the chiral HPLC analysis (Table 4, entries 1, 4, and 5). Unanimous formation of (R)-stereoisomers at the 3 position of 7 from (R,E)-6 led to confirmation that the proton attached to C1 was migrated to C3 from its si face, thus from the same back side if (R,E)-6

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

• desired (Z,E,Z)-configured triene 19. Again, we did not encounter formation of stereoisomers in the triene unit. The configuration of the triene was unequivocally assigned by analysis of coupling constants (J) and by measuring nuclear Overhauser effects (nOe). Finally, desilylation and global

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

• of this chemistry is its ability to provide 1,2-cis glycosides with good stereoselectivity, as these glycosides still remain among the most challenging stereoisomers to synthesize as C2 neighboring group participation is not possible [40]. In fact, the access to 1,2-cis glycosides is considered a

From chemical metabolism to life: the origin of the genetic coding process

• Antoine Danchin

Beilstein J. Org. Chem. 2017, 13, 1119–1135, doi:10.3762/bjoc.13.111

• either on the right or on the left to prevent collisions or traffic jams. Any accidental local enrichment of a particular shape would be symmetry-breaking. This contingent pick is a straightforward explanation of the ubiquitous presence of one family of stereoisomers, L-amino acids, in proteins

• structure but diverse 3D structures, selecting only a very limited panel of stereoisomers among those possible (for example, there are four isomers of the amino acid isoleucine, but only L-isoleucine is proteinogenic, while D-isoleucine and L- and D-allo-isoleucine are not). This ubiquitous dissymmetry is

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

• carried out on two possible stereoisomers, (4R,6R,αS)-1 and (4R,6R,αR)-1. MMFF conformational search and subsequent geometry optimization using the DFT-D3 method at the B3LYP-D3/6-31G(d) level followed by a higher level of energy calculations at the B3LYP-D3/def2-TZVP level afforded 14 and 11 distinctive

• conformers of both stereoisomers were subjected to TDDFT calculations of the electronic circular dichroism (ECD) spectra. As shown in Figure 3, the calculated ECD spectra of (4R,6R,αS)-1 and (4R,6R,αR)-1 were similar to one another and both in good agreement with the measured spectrum of 1, which indicated a

Conformational study of L-methionine and L-cysteine derivatives through quantum chemical calculations and ³J_HH coupling constant analyses

• Weslley G. D. P. Silva,
• Carolyne B. Braga and
• Roberto Rittner

Beilstein J. Org. Chem. 2017, 13, 925–937, doi:10.3762/bjoc.13.94

• linkage. Each structure of the N-acetylated derivatives presented two possible stereoisomers, i.e., where the dihedral angle θ [C−N−C(O)−C] (Figure 6) can be both 0° and 180°. Thus, the resulting 22 and 16 possible geometries of 3 and 4, respectively, were optimized. The optimization calculations gave

Fluorinated cyclohexanes: Synthesis of amine building blocks of the all-cis 2,3,5,6-tetrafluorocyclohexylamine motif

• Tetiana Bykova,
• Nawaf Al-Maharik,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2017, 13, 728–733, doi:10.3762/bjoc.13.72

• Tetiana Bykova Nawaf Al-Maharik Alexandra M. Z. Slawin David O'Hagan School of Chemistry, University of St Andrews, North Haugh, St Andrews, KY16 9ST, UK 10.3762/bjoc.13.72 Abstract This paper reports the synthesis of three amine stereoisomers 5a–c of the tetrafluorocyclohexyl ring system, as

• moieties were then converted to different stereoisomers of the tetrafluorocyclohexyl ring system, and then reductive hydrogenation of the nitrile delivered three amine stereoisomers. It proved necessary to place a methyl group on the cyclohexane ring in order to stabilise the compound against subsequent HF

Studies directed toward the exploitation of vicinal diols in the synthesis of (+)-nebivolol intermediates

• Runjun Devi and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2017, 13, 571–578, doi:10.3762/bjoc.13.56

• chromans have become attractive synthetic targets in academia and pharmaceutical industry [1]. Nebivolol (1, Figure 1) is a chroman-based antihypertensive drug that was first reported in the racemic form [2][3]. Chiral HPLC was subsequently employed to access various stereoisomers of 1 in enantiomerically

• pure form [4][5]. Out of the ten possible stereoisomers of 1, (S,R,R,R)-nebivolol or (+)-nebivolol (1a, Figure 1) was found to be a potent β1-adrenergic receptor blocker [2][3]. On the other hand, the corresponding enantiomeric form, (R,S,S,S)-nebivolol or (−)-nebivolol (1b, Figure 1) was found to be

• first use of the Sharpless asymmetric dihydroxylation as the sole source of chirality for the synthesis of nebivolol intermediates. The chroman-based antihypertensive drug nebivolol, its biologically active stereoisomers and late-stage intermediates for its synthesis. Synthetic strategies toward late

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

• the 1H and 13C NMR data (Supporting Information File 1, Table S3) compounds 8 and 9 were supposed to be stereoisomers. NMR spectral data of compound 8 were identical with those of (+)-isosarcophine ([α]D20 +235.3) reported by Kusumi et al. [32], so 8 is established as (+)-isosarcophine. The

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

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

• so in principle, 1024 (210) different stereoisomers are possible. Yet, nature reliably assembles only one stereoisomer (at least at detectable levels), at once revealing the strict stereocontrol underpinning the pathway and the importance of synthesizing this particular version. Indeed, the crystal

• increased access to the chain extension intermediates. How the KRs were shown to participate in epimerization will be detailed below. Ketoreductases KR domains catalyze the stereospecific reduction of the C-3-ketone groups arising from the chain extension reaction, to give both possible stereoisomers of the

Synthesis of structurally diverse 3,4-dihydropyrimidin-2(1H)-ones via sequential Biginelli and Passerini reactions

• Andreas C. Boukis,
• Baptiste Monney and
• Michael A. R. Meier

Beilstein J. Org. Chem. 2017, 13, 54–62, doi:10.3762/bjoc.13.7

• Passerini reactions, four different stereoisomers (RR, RS, SR, SS) are thus obtained. The homo (RR, SS) and hetero pairs (RS, SR) are diastereomers with slightly different physical properties. In the context of our experimental NMR data, it is thus fair to assume that the peak splitting is caused by these

• identified. Stereoisomers formed in the Biginelli–Passerini tandem reaction. The homo (RR, SS) and hetero pairs (RS, SR) are diastereomers. a) Proposed mechanism of the Biginelli reaction according to [6]. b) Proposed mechanism of the Passerini reaction. Biginelli reactions for the preparation of DHMP

Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

• Salvatore V. Giofrè,
• Santa Cirmi,
• Raffaella Mancuso,
• Francesco Nicolò,
• Giuseppe Lanza,
• Laura Legnani,
• Agata Campisi,
• Maria A. Chiacchio,
• Michele Navarra,
• Bartolo Gabriele and
• Roberto Romeo

Beilstein J. Org. Chem. 2016, 12, 2793–2807, doi:10.3762/bjoc.12.278

• derivatives and that the Z compounds give only cycloadducts 6, while E lead only to adducts 7. The 1H NMR spectrum of the crude reaction mixture shows the stereoisomers 6a–f as the main products, while stereoisomers 7a–f are present as minor components or only in traces. The cycloaddition reaction showed

Computational methods in drug discovery

• Sumudu P. Leelananda and
• Steffen Lindert

Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267

• identifying the most native-like docking poses. SPORES is one program that is used for the prepossessing of proteins for protein–ligand docking. It can generate different protonated states, tautomeric states and stereoisomers for protein structures [152]. LigPrep from the Schrodinger Suite [153] allows to

Biomimetic synthesis and HPLC–ECD analysis of the isomers of dracocephins A and B

• Viktor Ilkei,
• András Spaits,
• Anita Prechl,
• Áron Szigetvári,
• Zoltán Béni,
• Miklós Dékány,
• Csaba Szántay Jr,
• Judit Müller,
• Árpád Könczöl,
• Ádám Szappanos,
• Attila Mándi,
• Sándor Antus,
• Ana Martins,
• Attila Hunyadi,
• György Tibor Balogh,
• György Kalaus (†),
• Hedvig Bölcskei,
• László Hazai and
• Tibor Kurtán

Beilstein J. Org. Chem. 2016, 12, 2523–2534, doi:10.3762/bjoc.12.247

• , Eötvös utca 6, H-6720 Szeged, Hungary 10.3762/bjoc.12.247 Abstract Starting from racemic naringenin ((±)-1), a mixture of dracocephin A stereoisomers 6-(2”-pyrrolidinone-5”-yl)naringenin (±)-2a–d and its regioisomer, dracocephin B 8-(2”-pyrrolidinone-5”-yl)naringenin (±)-3a–d originally isolated from

• Dracocephalum rupestre, have been synthesized in a one-pot reaction. The separation of 2a–d and 3a–d was achieved by preparative HPLC. The four stereoisomers of each natural product were separated by analytical chiral HPLC and their absolute configuration was studied by the combination of HPLC–ECD measurements

• stereoisomers by Ren et al. in 2008 from Dracocephalum rupestre [2], which is an herb widely distributed throughout western China and used in folk medicine for the treatment of various conditions including cold, cough, icterohepatitis and laryngalgia. Dracocephins A (±)-2a–d and B (±)-3a–d have been found to be

Construction of bis-, tris- and tetrahydrazones by addition of azoalkenes to amines and ammonia

• Artem N. Semakin,
• Aleksandr O. Kokuev,
• Yulia V. Nelyubina,
• Alexey Yu. Sukhorukov,
• Petr A. Zhmurov,
• Sema L. Ioffe and
• Vladimir A. Tartakovsky

Beilstein J. Org. Chem. 2016, 12, 2471–2477, doi:10.3762/bjoc.12.241

• isomers depends on the substitution pattern and solvent. For example, the E,E-isomer was predominant for 2a in DMSO-d6, while in CDCl3 E,Z-2a was the major isomer. The assignment of stereoisomers was performed using known correlations between the configuration of the C=N bond and the chemical shift of

Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides

• Ilya V. Efimov,
• Marsel Z. Shafikov,
• Nikolai A. Beliaev,
• Natalia N. Volkova,
• Tetyana V. Beryozkina,
• Wim Dehaen,
• Zhijin Fan,
• Viktoria V. Grishko,
• Gert Lubec,
• Pavel A. Slepukhin and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2016, 12, 2390–2401, doi:10.3762/bjoc.12.233

• . The isoxazolines transform to aromatic isoxazoles 4 during purification. Fortunately, we were able to isolate the products of the reaction of β-imidazolyl enamines 1a,b with hydroxamoyl chlorides 2a,d,g, and the novel imidazolylisoxazolines 3a–c as pure stereoisomers in 67, 65 and 21% yields

β-Amino functionalization of cinnamic Weinreb amides in ionic liquid

• Yi-Ning Wang,
• Guo-Xiang Sun and
• Gang Qi

Beilstein J. Org. Chem. 2016, 12, 2372–2377, doi:10.3762/bjoc.12.231

• interesting phenomenon can be seen; namely, the difference of the proton chemical shifts of the hydrogen atoms of the nitrobenzenesulfonylamines. Compared with the chemical shifts of these protons belonging to the syn-stereoisomers, the signals of the same kind of protons of the anti-stereoisomers move to

• addition, because of the resonance structures (Scheme 4), the hydrogen bonding can be further strengthened by the oxygen which is more electronegative. As a result, the chemical shifts of these protons belonging to the anti-stereoisomers can move to much lower fields than those of the similar hydrogen

• atoms of not only the syn-stereoisomers but also the β-amino compounds derived from α,β-unsaturated ketones. This hypothesis can be supported by an unexpected transformation. When aziridine 7-B was purified by flash column chromatography, part of the aziridine ring was opened by a chlorine anion to form

Useful access to enantiomerically pure protected inositols from carbohydrates: the aldohexos-5-uloses route

• Felicia D’Andrea,
• Giorgio Catelani,
• Lorenzo Guazzelli and
• Venerando Pistarà

Beilstein J. Org. Chem. 2016, 12, 2343–2350, doi:10.3762/bjoc.12.227

• level is required. For this reason, many research efforts were directed toward the investigation of the structure–activity relationship (SAR) between inositol phosphates and biomacromolecules. These studies require various regio- and stereoisomers of inositol phosphates [6][7] and have prompted the

• material but differs from previous work in that it is metal-free. The first application of this approach was described by Kiely [31][32] who obtained a sample of myo-inositol in a mixture with other non characterised stereoisomers by treating D-xylo-hexos-5-ulose [31] and its 6-phosphate [32] with 0.1 N

A detailed view on 1,8-cineol biosynthesis by Streptomyces clavuligerus

• Jan Rinkel,
• Patrick Rabe,
• Laura zur Horst and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 2317–2324, doi:10.3762/bjoc.12.225

• representing various stereoisomers and constitutional isomers with different positioning of olefinic double bonds or alcohol functions are known just for sesquiterpenes [11]. The structural diversity of terpenoids can be further increased by the action of tailoring enzymes such as cytochrome P450

A new and expeditious synthesis of all enantiomerically pure stereoisomers of rosaprostol, an antiulcer drug

• Wiesława Perlikowska,
• Remigiusz Żurawiński and
• Marian Mikołajczyk

Beilstein J. Org. Chem. 2016, 12, 2234–2239, doi:10.3762/bjoc.12.215

• Wieslawa Perlikowska Remigiusz Zurawinski Marian Mikolajczyk Department of Heteroorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland 10.3762/bjoc.12.215 Abstract Four enantiomerically pure stereoisomers of

• to 64%. The remaining two stereoisomers, (−)-1b and (+)-1d, were obtained from (−)-1a and (+)-1c in 71 and 68% yield, respectively, by a two-reaction sequence, in which a Mitsunobu inversion of configuration at C-5 was the key step. Keywords: antiulcer drug; chiral resolution; rosaprostol

• stereostructure–bioactivity relationship in biologically active compounds [18][19], including selected prostanoids [20][21][22], we decided to synthesize all four rosaprostol stereoisomers 1a–d in enantiomerically pure form (Figure 2). The two rosaprostol stereoisomers 1c and 1d have an absolute configuration at