Indium-mediated C-allylation of melibiose

• Christian Denner,
• Manuel Gintner,
• Hanspeter Kählig and
• Walther Schmid

Beilstein J. Org. Chem. 2019, 15, 2458–2464, doi:10.3762/bjoc.15.238

• of this post-transition metal for the elongation of carbohydrates [3][4][5]. Additional contributions were reported in the literature by Paquette and co-workers concerning indium-mediated reactions in water and their stereochemistry [6][7]. Based on these findings this elongation method has been

In water multicomponent synthesis of low-molecular-mass 4,7-dihydrotetrazolo[1,5-a]pyrimidines

• Irina G. Tkachenko,
• Sergey A. Komykhov,
• Vladimir I. Musatov,
• Svitlana V. Shishkina,
• Viktoriya V. Dyakonenko,
• Vladimir N. Shvets,
• Mikhail V. Diachkov,
• Valentyn A. Chebanov and
• Sergey M. Desenko

Beilstein J. Org. Chem. 2019, 15, 2390–2397, doi:10.3762/bjoc.15.231

• the final confirmation of the structure and to establish the relative stereochemistry of both stereoisomers. NOESY cross-peaks between signals of NH and OH protons revealed that A and B are in fact stereoisomers, rejecting the regioisomeric structure 14’. The different 3J values between 6-H and 7-H

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• generate a vast number of (poly)cyclic hydrocarbon scaffolds. Remarkably, this complex chemical reaction, comprising changes in bonding, hybridization as well as the introduction of specific stereochemistry, is performed in a single reaction cascade without consumption of a cofactor [11]. In this review we

Perspective isomorphs – a new classification of molecular structures based on artistic and chemical concepts

• Jannis Neumann,
• Ansgar Schnurr and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2019, 15, 2319–2326, doi:10.3762/bjoc.15.224

• substances by transforming their structural information into an explicit character sequence for identification. The information is given in terms of layers around the atoms and their bond connectivity, tautomeric information, isotope information, stereochemistry, and electronic charge information. In

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• substrates was reported by Yu and co-workers (Scheme 13) [50]. Enantioenriched benzyl fluorides were obtained by aid of a chiral α-amino amide transient directing group (TDG). Notably, the condensation of this bulky amino amide with the aldehyde led to control of the stereochemistry of the C–H insertion step

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

• ][172][174][176][183][186][227][229]. There are very few papers reporting the aforementioned reaction occurring in aqueous conditions [175] most likely as a result of the poor solubility of fulvene derivatives in water [175]. Although the stereochemistry of DACs can usually be predicted by the ‘endo

• ] or diphenylfulvene [20][103][114][133][163][180]. In each instance, the endo stereochemistry of the cycloadduct is dominant [91][176][180], indicating that the fulvene substituents in the exocyclic C6 position are too distal to impact the stereoselectivity [76][229]. There are documented cases of

Isolation and characterisation of irinans, androstane-type withanolides from Physalis peruviana L.

• Annika Stein,
• Dave Compera,
• Bianka Karge,
• Mark Brönstrup and
• Jakob Franke

Beilstein J. Org. Chem. 2019, 15, 2003–2012, doi:10.3762/bjoc.15.196

• reported so far [14]. To elucidate the relative stereochemistry of irinans A (2) and B (3), we analysed NOESY data (Figure 2). In the case of irinan A (2), the β configuration of OH-4 was deduced by the NOESY correlation OH-4/CH3-19. OH-14 was assigned as α based on the correlations OH-14/H-12α and H-9/H

• -12α. The 5,6-epoxide was determined as β by a correlation from H-6 to H-3. These assignments are in complete agreement with the relative stereochemistry of 4ß-hydroxywithanolide E (1). In irinan B, the configuration of OH-14 could not be unambiguously inferred from NOE data due to the signal overlap

• of H-15 with H-12 and other protons. As an alternative, OH-14 α configuration was deduced from the chemical shifts of C-12 and C-9, which experience a strong shielding γ-gauche effect for OH-14α configurations [21]. These data indicate a relative stereochemistry of irinan B matching withanolide F (5

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

• the desired stereochemistry of the C-7 benzylic hydroxy group. Compound 46 was converted to triptonide 2 by Alder periodate reaction (NaIO4, 74%), and a sequencing m-CPBA epoxidation and basic hydrogen peroxide oxidation (H2O2/OH−) procedure (two steps, 28%). Finally, sodium borohydride reduction of 2

Archangelolide: A sesquiterpene lactone with immunobiological potential from Laserpitium archangelica

• Silvie Rimpelová,
• Michal Jurášek,
• Lucie Peterková,
• Jiří Bejček,
• Vojtěch Spiwok,
• Miloš Majdl,
• Michal Jirásko,
• Miloš Buděšínský,
• Juraj Harmatha,
• Eva Kmoníčková,
• Pavel Drašar and
• Tomáš Ruml

Beilstein J. Org. Chem. 2019, 15, 1933–1944, doi:10.3762/bjoc.15.189

• takes place remarkably differs from that in compound 2 and thapsigargin. This is very likely due to stereochemistry on the lactone ring connection at C7 and the absence of a hydroxy group at the same position. The steric circumstances and the presence of the α-carbonyl group makes the tertiary C11

Application of chiral 2-isoxazoline for the synthesis of syn-1,3-diol analogs

• Juanjuan Feng,
• Tianyu Li,
• Jiaxin Zhang and
• Peng Jiao

Beilstein J. Org. Chem. 2019, 15, 1840–1847, doi:10.3762/bjoc.15.179

• gave 16 in 87% yield [26][27]. The absolute stereochemistry of 16 was confirmed by crystal structure analysis [72] and the specific rotation [28] of 17. Centimeter-long prismatic single crystals of 17 were obtained by slow evaporation of a petroleum solution. Starting from 9, we tested several

Synthesis of a [6]rotaxane with singly threaded γ-cyclodextrins as a single stereoisomer

• Jason Yin Hei Man and
• Ho Yu Au-Yeung

Beilstein J. Org. Chem. 2019, 15, 1829–1837, doi:10.3762/bjoc.15.177

• synthesis of 6R is stereoselective and only one stereoisomer was formed, probably due to the cooperative interactions between the CB[6] and the γ-CD on the fully occupied axle of 6R. These findings will provide better insight on the use of intercomponent interactions to control the stereochemistry of

The cyclopropylcarbinyl route to γ-silyl carbocations

• Xavier Creary

Beilstein J. Org. Chem. 2019, 15, 1769–1780, doi:10.3762/bjoc.15.170

• isomeric mixture of esters 16. Subsequent reduction with lithium aluminum hydride gave a mixture of alcohols 17 and 18, which could be readily separated by silica gel chromatography. The assignment of stereochemistry of these isomers was based on shielding effects in both 1H and 13C NMR spectra. For

• . Stereochemistry of the alcohol 58 was established by long-range 19F coupling to the cis-trimethylsilyl group hydrogens (JH-F = 0.9 Hz). Long-range 19F coupling to the TMS methyl groups of 58 was also observed in the 13C NMR spectrum (JC-F = 2.1 Hz) [64][65]. This long-range 19F coupling is not observed when the

• borohydride reduction of the ester functionality of 63 gave a separable mixture of alcohols 64 and 65. The stereochemistry of the product 65 was established using nOe studies. Cyano to carbomethoxy conversion in 65 to give alcohol 66 was straightforward. Triflate derivatives 67 and 68 were prepared since

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• stereochemistry, they were synthesized from the aziridine ketone (2S,1'R)-36 readily available from Weinreb amide (2S,1'R)-18 which already contained the required configuration at C2 (Scheme 11) [47]. Introduction of the 3R configuration in xestoaminol C and 3S in its epimer was achieved by stereoselective

• diversified biological activity. From several synthetic approaches to ᴅ-ribo-phytosphingosine [79] application of the aziridine aldehyde (2S,1'R)-6 provided (2S,3S,4R)-110 in four steps with full control of stereochemistry (Scheme 29) [80]. Since the 2S absolute configuration of the final product was already

Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)

• Małgorzata Urbańczyk,
• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Jerzy Góra,
• Rafał Latajka and
• Norbert Sewald

Beilstein J. Org. Chem. 2019, 15, 1581–1591, doi:10.3762/bjoc.15.162

• conformation of the molecule as well an on the stereochemistry of amino acid residues. The desired monoglycosylated analogues with acetylated amino termini and the carboxy termini in form of N-methylamide have been synthesized. Conformational nuclear magnetic resonance (NMR) studies of the designed analogues

• have shown a strong influence of the stereochemistry of amino acid residues on the peptide chain stability, which could be connected to the antifreeze activity of these compounds. A better understanding of the mechanism of action of antifreeze glycopeptides would allow applying these materials, e.g

• the saccharide moiety is conformationally well-defined by the peptide backbone and the whole structure adopts a polyproline II (PP II) helix [17]. Antifreeze activity strongly relies on the stereochemistry of the amino acid residues. Earlier studies have shown that AFGP analogues containing either an

Enantioselective PCCP Brønsted acid-catalyzed aza-Piancatelli rearrangement

• Gabrielle R. Hammersley,
• Meghan F. Nichol,
• Helena C. Steffens,
• Jose M. Delgado,
• Gesine K. Veits and
• Javier Read de Alaniz

Beilstein J. Org. Chem. 2019, 15, 1569–1574, doi:10.3762/bjoc.15.160

• rearrangement (Figure 1). Analogous to the Nazarov cyclization, controlling the absolute stereochemistry can be achieved by governing the direction of the conrotatory electrocyclization, clockwise vs counterclockwise [32][33][34]. Despite the direct relationship to the asymmetric Nazarov cyclization, however

• , it was not until 2016 that the first asymmetric aza-Piancatelli reaction was described. To control the absolute stereochemistry of the aza-Piancatelli rearrangement, Rueping [35], Sun [36], and Patil [37] independently demonstrated that chiral phosphoric acids can be used as an enantioselectivity

• aza-Piancatelli reaction, we sought to identify other asymmetric catalytic systems capable of controlling the absolute stereochemistry. To this end, we envisioned that the chiral pentacarboxycyclopentadiene (PCCP) Brønsted acid catalyst (8) recently developed by the Lambert lab might be suitable

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

• chromatography, for instance, compounds E-11m and Z-11m (Table 3, entry 9 and Supporting Information File 1). The E/Z-stereochemistry of compounds 11 was determined on the basis of the values of spin–spin interaction constants of vinyl protons, which were 13–14 Hz for Z-isomers and 17–18 Hz for E-isomers (see

Synthesis of pyrrolo[1,2-a]quinolines by formal 1,3-dipolar cycloaddition reactions of quinolinium salts

• Anthony Choi,
• Rebecca M. Morley and
• Iain Coldham

Beilstein J. Org. Chem. 2019, 15, 1480–1484, doi:10.3762/bjoc.15.149

• to undergo reaction with the ylides derived from the salts 4 and 5. In both cases, very good yields of the tetracyclic adducts 9 and 10 were obtained after heating for only 1 h (Scheme 3). The relative stereochemistry of the adduct 9 was determined by single crystal X-ray analysis (Figure 2). To

• with N-methylmaleimide in the presence of triethylamine in methanol to give the desired adducts 15a and 15b as single stereoisomers (Scheme 5). The stereochemistry of product 15a was confirmed by single crystal X-ray analysis (see Supporting Information File 1) and matches the relative configuration of

Fluorine-containing substituents: metabolism of the α,α-difluoroethyl thioether motif

• Andrea Rodil,
• Alexandra M. Z. Slawin,
• Nawaf Al-Maharik,
• Ren Tomita and
• David O’Hagan

Beilstein J. Org. Chem. 2019, 15, 1441–1447, doi:10.3762/bjoc.15.144

• we could not determine the absolute stereochemistry of the predominant enantiomer, it was clear from the assay that there was a significant enantiomeric ratio (4:1) of 6 which translates to a 60% enantiomeric excess (ee, see Supporting Information File 1). We note that there have been chemical

• chemical oxidation of thioether 5. The resultant enantiomeric ratio for 11 was determined to be 3.3:1, which translates to a 54% ee (absolute stereochemistry not determined). Again, the sulfoxidation shows a significant stereochemical bias. The stability of the aryl thioethers can be contrasted with the

Introduction of an isoxazoline unit to the β-position of porphyrin via regioselective 1,3-dipolar cycloaddition reaction

• Xiujun Liu,
• Xiang Ma and
• Yaqing Feng

Beilstein J. Org. Chem. 2019, 15, 1434–1440, doi:10.3762/bjoc.15.143

• -dichlorophenyl- or 2,4,6-trimethylphenyl nitrile oxides were used to react with 2 at 110 °C for 12 hours in toluene. Generally, two products with different positions (C4 or C5) of isoxazoline connected to the β-position of porphyrin should be obtained if the stereochemistry was not considered (Scheme 1) [43

Borylation and rearrangement of alkynyloxiranes: a stereospecific route to substituted α-enynes

• Ruben Pomar Fuentespina,
• José Angel Garcia de la Cruz,
• Gabriel Durin,
• Victor Mamane,
• Jean-Marc Weibel and
• Patrick Pale

Beilstein J. Org. Chem. 2019, 15, 1416–1424, doi:10.3762/bjoc.15.141

• rearrangement of the so-formed alkynyloxiranyl borates. This stereospecific process overall transfers the cis or trans-stereochemistry of the starting alkynyloxiranes to the resulting 1,3-enynes. Keywords: boron; enyne; lithium; oxirane; rearrangement; Introduction Lithiated oxiranes are useful intermediates

• isomers. The cis-configured compound cis-1b readily reacted with pinacol phenylboronate 2c under the conditions set up above, providing enyne 4 as the sole product in high yield (Table 2, entry 1). NMR analysis revealed the Z-stereochemistry of this enyne [31]. In contrast, the trans-isomer trans-1b

• also reactive, but longer reaction times were required, probably due to steric hindrance at some stage of the rearrangement (vide infra). Both isomers exclusively afforded the expected E or Z tetrasubstituted alkenes 13 in high yields (Table 3, entries 7 and 8). Stereochemistry and mechanism Based on

Anomeric sugar boronic acid analogues as potential agents for boron neutron capture therapy

• Daniela Imperio,
• Erika Del Grosso,
• Silvia Fallarini,
• Grazia Lombardi and
• Luigi Panza

Beilstein J. Org. Chem. 2019, 15, 1355–1359, doi:10.3762/bjoc.15.135

• moderate yield. Unfortunately, we isolated as main side product the known elimination compound 7a [16], which further confirms the strong tendency of β-alkoxyboronic acids to give rise to elimination. The stereochemistry of the newly formed stereocenter was inferred from the coupling constant between H-3

Genomics-inspired discovery of massiliachelin, an agrochelin epimer from Massilia sp. NR 4-1

• Jan Diettrich,
• Hirokazu Kage and
• Markus Nett

Beilstein J. Org. Chem. 2019, 15, 1298–1303, doi:10.3762/bjoc.15.128

• product, which was named massiliachelin, corresponds to the assembly line encoded by the identified siderophore locus. Keywords: agrochelin; genome mining; Massilia; massiliachelin; siderophore; stereochemistry; Introduction In recent years, chemical investigations as well as genomics led to the

• [23]. An analysis of the analogous enzymes in micacocidin [13], yersiniabactin [16], and enantio-pyochelin [24] biosynthesis confirmed that the presence or absence of this feature allows a reliable prediction of the stereochemistry in this position (Table S1, Supporting Information File 1). In every

• stereochemistry at the C2 position derived from L-cysteine. This is because the MicC homolog from Massilia sp. NR 4-1 features only a single adenylation domain for the activation of L-cysteine, which corresponds to the micacocidin and yersiniabactin assembly lines [13][16]. An inspection of the ketoreductase (KR

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• stepwise Pd(II)-catalyzed cascade process or a [4 + 2] cycloaddition reaction, both providing the cis stereochemistry at C-2 and C-3. When the reaction was carried out with the epimer of substrate 33 (having the 5β-hydroxy group), the cis stereochemistry was also achieved at the newly formed C-2 and C-3

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

• separable 76:24 mixture of alkylated tartrates 17 and 18, respectively. The relative stereochemistry was assigned by analogy with Seebach’s findings for substituted tartrates: that the diastereomer with the ring methine cis to the ester group (i.e., 17) always displays the higher chemical shift (≈5 ppm vs

• alkylating agent, which leads to the improved diastereoselectivity [43]. The trans stereochemistry assignment for the dialkylated products 34 follow from the observed equivalence of the acetonide methyl groups in all their proton and carbon NMR spectra. In Seebach's original studies, which established

• ) and cephalezomine C (44) [51]. In these latter natural products, the monoalkylated tartaric acid residues typically possess 2R,3S stereochemistry (Figure 2); one exception is cephalezomine D [51], which is the 3R-epimer of cephalezomine C (44). Since the chiral (R,R- S,S-) tartrate acetonides undergo

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• -diarylallylidene)oxindoles 132, respectively. Initially [114][115], using arylboronic acids 130 (R = Ar2), a variety of twenty-one diarylmethylene oxindoles 131 were obtained with good yields. When aryl iodide and arylboronic acids bearing different substituents are used, the expected stereochemistry of the

• controlled stereochemistry (Scheme 37). Indeed, they found that the PPh3 ligand promoted the formation of the E-isomer as the main compound while the t-BuXPhos ligand induced the preferential formation of the Z-isomer. As already mentioned before, this transformation is the result of a sequence of three