A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine

• Bettina Riedl and
• Walther Schmid

Beilstein J. Org. Chem. 2018, 14, 856–860, doi:10.3762/bjoc.14.71

• . In contrast to the thoroughly investigated properties of GalNAc, other stereoisomers have not been probed for biological or pharmaceutical activity, yet. Highly flexible synthetic routes are required to access and probe the entire compound class of 2-amino-2-deoxysugars for further structure–activity

• of the four desired stereogenic centers. By extending compound 5 via a Horner–Wadsworth–Emmons (HWE) reaction [15] and subsequent stereoselective introduction of the corresponding nitrogen functionality, a route to four different 2-amino sugar stereoisomers has been elaborated. Results and Discussion

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• Vorbrüggen coupling reaction [66], the synthesis of C-nucleosides typically gives a mixture of stereoisomers (α and β) at the anomeric carbon [48][49][54][62][67][68]. Since the naturally occurring nucleosides (and most biologically active nucleosides) are β-anomers, achieving 100% stereospecificity in C–C

Volatiles from the xylarialean fungus Hypoxylon invadens

• Jeroen S. Dickschat,
• Tao Wang and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 734–746, doi:10.3762/bjoc.14.62

• mass spectrum and the retention index match reported data. The comparison of retention indices is particularly important, if different stereoisomers need to be considered, because stereoisomers may have very similar mass spectra, as observed for the sesquiterpenes α-muurolene (3), α-amorphene (4), and

• ; MS (EI, 70 eV) m/z (%): 218 (81) [M]+, 204 (13), 203 (100), 137 (53), 136 (17), 108 (21), 67 (26), 43 (23), 39 (13). Structures of the widespread fungal volatiles oct-1-en-3-ol (1) and 6-pentyl-2H-pyran-2-one (2), the stereoisomers α-muurolene (3), α-amorphene (4) and α-cadinene (5), and the

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

• Denisa Vargová,
• Rastislav Baran and
• Radovan Šebesta

Beilstein J. Org. Chem. 2018, 14, 553–559, doi:10.3762/bjoc.14.42

• medicines and can be obtained by organocatalytic Michael additions. We show here the stereoselective synthesis of 4-methylpregabalin stereoisomers using a Michael addition of dimethyl malonate to a racemic nitroalkene. The key step of the synthesis operates as a kinetic resolution with a chiral squaramide

• catalyst. Furthermore, specific organocatalysts can provide respective stereoisomers of the key Michael adduct in up to 99:1 er. Keywords: kinetic resolution; Michael addition; organocatalysis; pregabalin; squaramide; Introduction Asymmetric organocatalysis has considerably broadened possibilities for

• have measured specific optical rotation for compound 1 to be [α]D20 −2.6 (c 0.95, MeOH). This value corresponds better with literature data, which for the (3R,4R)-isomer states [α]D20 −5.3 whereas for (3R,4S) [α]D20 +14.9. Conclusion We have shown that 4-methylpregabalin stereoisomers can be

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• compounds a synthesis of references was required. For one of the main compounds, 5-hydroxy-4,6-dimethyloctan-3-one, the relative and absolute configuration was determined by synthesis of all eight stereoisomers and gas chromatographic analysis using a homochiral stationary phase. Another identified new

• –Wadsworth–Emmons reaction with triethyl 2-phosphonopropionate (19) yielded ethyl (E)-2,4-dimethylhex-2-enoate (20) as a separable mixture of E and Z stereoisomers (E/Z = 10:1). The purified E diastereomer was reduced with DIBAl-H to the corresponding alcohol 21. A PCC oxidation and addition of

• from an α-cleavage next to the alcohol function. To verify this structural proposal for 11a, racemic 2-methylbutanal (18) was reacted in an aldol addition with the enolate anion of pentan-3-one (23) which produced a racemic mixture of all four diastereomers 11a–d (Scheme 4). All eight stereoisomers of

Acid-catalyzed ring-opening reactions of a cyclopropanated 3-aza-2-oxabicyclo[2.2.1]hept-5-ene with alcohols

• Katrina Tait,
• Alysia Horvath,
• Nicolas Blanchard and
• William Tam

Beilstein J. Org. Chem. 2017, 13, 2888–2894, doi:10.3762/bjoc.13.281

• the nucleophile attacking from the open top face seen in 30, forming sole product 26a. If a free carbocation was formed as shown in path A, both stereoisomers 26a and 29 should have been observed, which was not evident. Also, if a free carbocation was formed the product likely would have undergone

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• the nucleophilic agents used in these reactions were usually prepared by reaction of sodium hydride or sodium ethoxide with a proper nucleophile, such as diethylamine, piperidine, pyrrole, ethanol, p-toluenesulfonamide, thiophenol and others. Depending on the reactants used, Z- or E-stereoisomers of

• the products 32 were obtained, but most commonly the reactions resulted in a mixture of stereoisomers (Scheme 22). The yield of the reaction was dependent on the kind of substrate and ranged from 14 to 68% [38]. The reaction involving organocopper compounds as carbon nucleophiles (R2CuLi, where R

Regioselective decarboxylative addition of malonic acid and its mono(thio)esters to 4-trifluoromethylpyrimidin-2(1H)-ones

• Sergii V. Melnykov,
• Andrii S. Pataman,
• Yurii V. Dmytriv,
• Svitlana V. Shishkina,
• Mykhailo V. Vovk and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2017, 13, 2617–2625, doi:10.3762/bjoc.13.259

• can be converted into saturated (2-oxohexahydropyrimidin-4-yl)acetic acid derivatives by mild hydrogenation of the endocyclic C=C double bond in the presence of Pd/C as catalyst. The cis-stereoisomers selectively formed upon reduction of the Michael-type products were structurally determined by X-ray

A permutation approach to the assignment of the configuration to diastereomeric tetrads by comparison of experimental and ab initio calculated differences in NMR data

• Przemysław J. Boratyński

Beilstein J. Org. Chem. 2017, 13, 2478–2485, doi:10.3762/bjoc.13.245

• diastereomers were studied and used quite extensively [8][10]. So far, however, assignments of configuration to four diastereomeric compounds, i.e., tetrads, were mostly performed by separately comparing selected pairs against each other. However, the availability of multiple stereoisomers should translate to

Diastereoselective Mannich reactions of pseudo-C₂-symmetric glutarimide with activated imines

• Tatsuya Ishikawa,
• Tomoko Kawasaki-Takasuka,
• Toshio Kubota and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2017, 13, 2473–2477, doi:10.3762/bjoc.13.244

• . Crystallographic analysis of the major diastereomer of 3a (some hydrogen atoms are omitted for clarity). Each color represents the following atoms: gray, carbon; white, hydrogen; blue, nitrogen; red, oxygen; green, fluorine; yellow, sulfur. Explanation of the construction of the main stereoisomers. Optimization of

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