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

Diels–Alder reactions in confined spaces: the influence of catalyst structure and the nature of active sites for the retro-Diels–Alder reaction

• Ángel Cantín,
• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2016, 12, 2181–2188, doi:10.3762/bjoc.12.208

• ] in where different stereoisomers could be obtained. Lewis-acid centers contained within the framework of zeolite beta (Zr-β, Sn-β) are useful catalysts in the Diels–Alder reaction for the production of bio-based terephthalic acid precursors, one of the monomers for the synthesis of polyethylene

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• stabilize the carbanion intermediate, also increases the stereocenter’s susceptibility to racemization under the reaction conditions. Moreover, enolate intermediates can adopt E- or Z-geometries that, upon protonation, generally lead to opposite stereoisomers. Because enantioselective protonation is a

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

• addition in more general terms and analyzed the addition reactions of allylmagnesium bromide both to 29 and 30. Notably, this route would allow to access all possible stereoisomers of the manzacidins, in agreement with the stereochemical diversity of this class of natural products. In detail, the synthesis

• urea-type cyclization precursor 19. Stereodivergent synthesis of 1,3-syn- and anti-tetrahydropyrimidinones [31]. Stereoselective synthesis of all possible stereoisomers of the manzacidin core amine by asymmetric addition to chiral tert-butanesulfinyl ketimines. Synthesis of the authentic cyclization

Efficient syntheses of climate relevant isoprene nitrates and (1R,5S)-(−)-myrtenol nitrate

• Sean P. Bew,
• Glyn D. Hiatt-Gipson,
• Graham P. Mills and
• Claire E. Reeves

Beilstein J. Org. Chem. 2016, 12, 1081–1095, doi:10.3762/bjoc.12.103

• ]. Evidently, to comprehensively investigate the role of individual IPNs within climate chemistry it is important that any synthetic protocol employed to generate IPNs affords either individual C=C stereoisomers or generates readily separable stereoisomers of the IPNs. Thus although the lack of synthetic

• purification afforded stereoisomers (E)-58 and (Z)-59 in a 2:1 ratio, respectively, and combined, unoptimized, 71% yield. Separation of the stereoisomers via flash column chromatography was straightforward. Pure (E)-58 and (Z)-59 were afforded with physicochemical properties essentially identical to those

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• haliangicin stereoisomers, which differed in the configuration of the three terminal double bonds in the tetraene moiety. Each of the isomers haliangicin, haliangicin B, haliangicin C and haliangicin D happened to be present with two different configurations around the epoxy group. The NOESY spectra showed

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• - and galacto-configured dialdehydes 66 were promoted by the triazolium carbene precatalyst 22 to produce single inosose stereoisomers 67 in high yields (Scheme 40) [57]. Stereospecific reduction and deprotection of the inosose derivatives furnished allo- and epi-inositol in good yields. The camphor

Aluminacyclopentanes in the synthesis of 3-substituted phospholanes and α,ω-bisphospholanes

• Vladimir A. D’yakonov,
• Alevtina L. Makhamatkhanova,
• Rina A. Agliullina,
• Leisan K. Dilmukhametova,
• Tat’yana V. Tyumkina and
• Usein M. Dzhemilev

Beilstein J. Org. Chem. 2016, 12, 406–412, doi:10.3762/bjoc.12.43

• BuPCl2, the reaction with 3-benzyl-1-ethylaluminacyclopentane 1f affords the corresponding phospholanes 2g,h with one of the isomers predominating (Table 1). In the case of 3-cyclohexyl- and 3-(сyclohex-3-en-1-yl)-1-phenylphospholanes (2d and 2e), the number of stereoisomers increases owing to the

• /methanol = 5:3:1) and characterized in a separate fraction (Scheme 4). It should be noted that the phosphorus signals of major intensity of 2-aryl phospholane oxides 8a, 8b, 8d, 8e, 8f, corresponding to one of the stereoisomers, are shifted upfield by ca. 5–7 ppm with respect to those of 3-aryl-substituted

• the proximate asymmetric centres at C-3 and С-3′. Ratios of stereoisomers were determined by HPLC method as 2:1 (see Supporting Information File 2, Figure S1). Organophosphorus compounds, including cyclic ones, are known to readily form complexes with transition metals, which are extensively studied

Diastereoselective synthesis of new O-alkylated and C-branched inositols and their corresponding fluoro analogues

• Charlotte Collet,
• Françoise Chrétien,
• Yves Chapleur and
• Sandrine Lamandé-Langle

Beilstein J. Org. Chem. 2016, 12, 353–361, doi:10.3762/bjoc.12.39

• ; Introduction Inositol is a trivial name used to describe cyclohexanehexol compounds. Nine stereoisomers exist differing in the relative orientation of the hydroxy groups, the most naturally abounding and biologically important is myo-inositol [1][2]. The chemistry of inositols has been the theme of several

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

• Sophie Letort,
• Sébastien Balieu,
• William Erb,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2016, 12, 204–228, doi:10.3762/bjoc.12.23

• organophosphates is to be considered important insofar as the individual stereoisomers of a neurotoxic agent do not share the same level of toxicity [20]. Sarin (compounds 14a and 14b, Figure 5), cyclosarin (compounds 15a and 15b, Figure 5) and tabun (compounds 16a and 16b, Figure 5) consist of a mixture of two

• enantiomers. Due to the presence of two chiral centers (the phosphorus atom and the carbon atom of the 1,2,2-trimethylpropyloxy group), soman presents four stereoisomers: C(S)P(S), C(R)P(S), C(S)P(R) and C(R)P(R) (compounds 17a–d, Figure 5). CDs can tune a reaction mechanism in two ways: (a) by creating a

• agent stereoisomers’ absolute configuration of the phosphorus atom was not firmly established. Thus, the van Hooidonk and Breebaart’s work dating from 1970, it is highly probable that they did not attributed the correct absolute configurations to the enantiomers of sarin, which means that the (S