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

• rosaprostol (1), an antiulcer drug, were efficiently synthesized from the enantiomers of 2-(dimethoxyphosphoryl)-3-hexylcyclopentanone (3) as chiral substrates. The latter were obtained by resolution of racemic 3 with (+)-(R)-1-(1-naphthyl)ethylamine. The conversion of (+)-3 into rosaprostol stereoisomer

• (−)-1a was accomplished in four steps in 56% overall yield. According to the same protocol, the second stereoisomer (+)-1c was obtained from (−)-3 in 55% overall yield. A slightly improved procedure of the last two steps of the transformation of (+)-3 into (−)-1a allowed an increase in the overall yield

• atom and step economy. Since a detailed evaluation of the biological activity and preclinical studies requires gram quantities of each stereoisomer of 1, we sought a shorter and more efficient approach to our targets. Herein we disclose a new total synthesis of all enantiomerically pure rosaprostol

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• already exist or followed [32][33][34][35][36][37][38][39]. Starting from the readily available C2-symmetric 1,5-diene 4 the 2,3,4,5-tetra-substituted THF diol 5 was obtained as a single stereoisomer with a yield of 84%, following the type A cyclization. Deprotection led to natural (+)-anhydro-D-glucitol

• prepared from commercially available neryl acetate (15). The auxiliary-controlled, permanganate-promoted oxidation of diene 16 proceeded selectively at low temperatures, affording the corresponding diastereomeric THF diols as an inseparable mixture (dr 7:1, major stereoisomer shown in Scheme 6). Compound

• of dienyne 57 proceeded rapidly and selectively at low temperatures, affording the corresponding diastereomeric THF diols as a separable mixture (dr 6:1, major stereoisomer shown in Scheme 13). Semi hydrogenation of the triple bond using the Lindlar catalyst gave the bis-homoallylic alcohol 58a

Chiral ammonium betaine-catalyzed asymmetric Mannich-type reaction of oxindoles

• Masahiro Torii,
• Kohsuke Kato,
• Daisuke Uraguchi and
• Takashi Ooi

Beilstein J. Org. Chem. 2016, 12, 2099–2103, doi:10.3762/bjoc.12.199

• reduced diastereoselectivity (Table 2, entries 1–4). Sterically demanding 2-tolualdehyde-derived imine 3f served as a good electrophile and the corresponding Mannich adduct 4af was isolated as virtually a single stereoisomer (Table 2, entry 5). 3-Thiophenyl aldimine 3g was also well tolerated, but a

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

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

• , Frost reported that using the same catalyst system, phenyltrimethoxysilane (49a) could be added to dimethyl itaconate (50) with modest enantioselectivity and without defining the absolute configuration of the major stereoisomer (Scheme 11b) [32]. Darses and Genet reported the highly enantioselective Rh

One-pot synthesis of enantiomerically pure N-protected allylic amines from N-protected α-amino esters

• Gastón Silveira-Dorta,
• Sergio J. Álvarez-Méndez,
• Víctor S. Martín and
• José M. Padrón

Beilstein J. Org. Chem. 2016, 12, 957–962, doi:10.3762/bjoc.12.94

• [6] but this is the first time it is described the synthesis of its (dia)stereoisomer (Z)-2b. The olefination with the non-stabilized ylide of pentadecyltriphenylphosphonium bromide led exclusively to (Z)-2c. Likewise, the results obtained for (E)-2a, the use of stabilized ylides (Table 2, entries 3

Enantioselective carbenoid insertion into C(sp³)–H bonds

• J. V. Santiago and
• A. H. L. Machado

Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87

• of 5 mol % of copper chloride salt, 6 mol % of ligand 1c and 6 mol % of sodium tetrakis[(3,5-tri-fluoromethyl)phenyl]borate (NaBARF). The cyclic sulfones 52 were obtained in good yields and excellent enantiomeric excesses (85–98%) favoring the cis-1,2-di-substituted stereoisomer (Table 5). The

• authors also performed the copper carbenoid insertion reaction to yield five-membered cyclic sulfones 54, under similar experimental conditions, in moderate yields and enantiomeric excesses of the trans stereoisomer (Table 6). Independent to the size of the product, the authors emphasize the low

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• be proven that (5'S,6'S)-GlyU 101 is the stereoisomer furnished in this reaction, so that no epimerisation at a later stage of the biosynthetic route is required for the formation of the A-90289 nucleoside antibiotics. Based on the elucidation of the LipK-mediated reaction, Van Lanen et al. then

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

• phosphonate group for the three methylfluorophosphonates do not result in fundamental changes of the dissociation constants. However, the rather slow hydrolysis rate of P(R)-sarin can be explained by the space arrangement of this stereoisomer into the β-CD cavity. Sarin is the smallest of the three

• β-CD cavity could therefore be at the origin of the rather low reaction rate observed for this stereoisomer. Thus, in all the studies of Cabal, the P(R)-stereoisomers of soman, sarin and cyclosarin are faster hydrolyzed than the P(S)-stereoisomers in presence of CDs. Nevertheless, due to the

Organocatalytic and enantioselective Michael reaction between α-nitroesters and nitroalkenes. Syn/anti-selectivity control using catalysts with the same absolute backbone chirality

• Jose I. Martínez,
• Uxue Uria,
• Maria Muñiz,
• Efraím Reyes,
• Luisa Carrillo and
• Jose L. Vicario

Beilstein J. Org. Chem. 2015, 11, 2577–2583, doi:10.3762/bjoc.11.277

• therefore access to any stereoisomer at will from the same set of starting materials with full absolute and relative stereocontrol is not trivial. Previous reports show that the diastereoselection can be directed by different approaches that include the modification of reaction conditions [7][8][9], the

Lewis acid-promoted hydrofluorination of alkynyl sulfides to generate α-fluorovinyl thioethers

• Davide Bello and
• David O'Hagan

Beilstein J. Org. Chem. 2015, 11, 1902–1909, doi:10.3762/bjoc.11.205

• , giving the Z-stereoisomer 2c in 45% and 57% yields, respectively. We then maintained the phenyl moiety on the alkyne side of the sulfide, and replaced the benzyl group with a cyclohexyl fragment directly connected to the sulfur atom (compound 1d). This material allowed too for a stereoselective reaction

• , giving rise to the Z-stereoisomer of 2d in 47% and 68% yields, respectively. At this stage we decided to explore two simple variations of the groups directly connected to the ethynyl moiety, that are, a cyclopropyl group and the bulky tert-butyl group. Thus, we reacted cyclopropylethynyl(phenyl)sulfane

• completely stereoselective, furnished the Z-stereoisomer 2f in 40% and 62% yields, respectively, along with a 2% of difluorinated compound 4f. The formation of this byproduct could not be avoided; in fact lower temperatures or shorter reaction times did not change the outcome, and the contaminant 4f could

Stereochemistry of ring-opening/cross metathesis reactions of exo- and endo-7-oxabicyclo[2.2.1]hept-5-ene-2-carbonitriles with allyl alcohol and allyl acetate

• Piotr Wałejko,
• Michał Dąbrowski,
• Lech Szczepaniak,
• Jacek W. Morzycki and
• Stanisław Witkowski

Beilstein J. Org. Chem. 2015, 11, 1893–1901, doi:10.3762/bjoc.11.204

• allyl alcohol (4). The plausible mechanism of the formation of ROCM and ROMP products from exo- or endo-7-oxabicyclo[2.2.1]hept-5-ene-2-carbonitriles 1 or 2. For simplicity of the scheme, the reaction of only exo-stereoisomer 1 as a substrate is presented. Results of ROCM reactions of nitriles 1 and 2

Electrochemical oxidation of cholesterol

• Jacek W. Morzycki and
• Andrzej Sobkowiak

Beilstein J. Org. Chem. 2015, 11, 392–402, doi:10.3762/bjoc.11.45

• obtained in 32, 31, and 7% yields, respectively (Scheme 4). It is noteworthy that the reaction afforded a single stereoisomer of 11 or 12. Several important observations provided in the paper can give an idea on a plausible mechanism of cholesterol oxidation. First, in the absence of HMP and O2 only

Total synthesis of the proposed structure of astakolactin

• Takayuki Tonoi,
• Keisuke Mameda,
• Moe Fujishiro,
• Yutaka Yoshinaga and
• Isamu Shiina

Beilstein J. Org. Chem. 2014, 10, 2421–2427, doi:10.3762/bjoc.10.252

• stereoisomer (1’), with a Johnson–Claisen rearrangement, an asymmetric Mukaiyama aldol reaction, and our MNBA-mediated lactonization as key steps. It was found that the 1H and 13C NMR data of synthesized 1 and 1’ are not identical with those of the natural compound. Further studies to elucidate the complete

Photochemical approach to functionalized benzobicyclo[3.2.1]octene structures via fused oxazoline derivatives from 4- and 5-(o-vinylstyryl)oxazoles

• Ivana Šagud,
• Simona Božić,
• Željko Marinić and
• Marija Šindler-Kulyk

Beilstein J. Org. Chem. 2014, 10, 2222–2229, doi:10.3762/bjoc.10.230

• spectrum there are 5 signals in the region from 108 to 40 ppm. The doublet at 108 ppm indicates the structure with sp2-hybridized carbon (CH(A)) and the triplet at 44 ppm indicates the existence of one geminal carbon atom. The tetracyclic oxazoline stereoisomer rel-(2S)-10 undergoes spontaneously oxazoline

Synthesis and bioactivity of analogues of the marine antibiotic tropodithietic acid

• Patrick Rabe,
• Tim A. Klapschinski,
• Nelson L. Brock,
• Christian A. Citron,
• Paul D’Alvise,
• Lone Gram and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2014, 10, 1796–1801, doi:10.3762/bjoc.10.188

• product was sufficiently pure for its direct usage in a Diels–Alder reaction with tetrachlorocyclopropene, resulting in the adduct 19 as a single stereoisomer. The formation of only one stereoisomer is explainable by an E/Z isomerisation of 18 and a Diels–Alder reaction that only proceeds from (Z)-18, but

Streptopyridines, volatile pyridine alkaloids produced by Streptomyces sp. FORM5

• Ulrike Groenhagen,
• Michael Maczka,
• Jeroen S. Dickschat and
• Stefan Schulz

Beilstein J. Org. Chem. 2014, 10, 1421–1432, doi:10.3762/bjoc.10.146

• the diastereomeric mixture of Wittig salts. Conclusively, 10 must be the last possible 1Z,3Z-stereoisomer. Both compounds 10 and 11 could not be isolated in pure form, but their mass spectra and retention times were identical to those of the natural products. The mass spectrum of compound 8 indicated

Synthesis of a sucrose dimer with enone tether; a study on its functionalization

• Zbigniew Pakulski,
• Norbert Gajda,
• Magdalena Jawiczuk,
• Jadwiga Frelek,
• Piotr Cmoch and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2014, 10, 1246–1254, doi:10.3762/bjoc.10.124

• of 10. Indeed, treatment of enone 10 with Zn(BH4)2 under the standard conditions afforded allylic alcohol 11 as single stereoisomer in 65% yield. Based on our model, the R-configuration might be safely assigned to the new stereogenic center. This assignment was further verified independently by

• circular dichroism spectroscopy (CD) using the in situ dimolybdenum methodology (see next chapter). Next steps of the synthesis consisted of the protection of the C6–OH as benzyl ether (to 12) and osmylation of the double bond. The cis-dihydroxylation provided, as single stereoisomer, a diol to which

Allenylphosphine oxides as simple scaffolds for phosphinoylindoles and phosphinoylisocoumarins

• G. Gangadhararao,
• Ramesh Kotikalapudi,
• M. Nagarjuna Reddy and
• K. C. Kumara Swamy

Beilstein J. Org. Chem. 2014, 10, 996–1005, doi:10.3762/bjoc.10.99

• compound 7 was further confirmed by X-ray crystallography (Figure 2). The C=CHMe distance of 1.317(2) Å clearly indicates a double bond between these two carbon atoms. The other stereoisomer in which the methyl group is trans to the nitrogen was not observed. Interestingly though, the removal of the acyl

Structure elucidation of female-specific volatiles released by the parasitoid wasp Trichogramma turkestanica (Hymenoptera: Trichogrammatidae)

• Armin Tröger,
• Teris A. van Beek,
• Martinus E. Huigens,
• Isabel M. M. S. Silva,
• Maarten A. Posthumus and
• Wittko Francke

Beilstein J. Org. Chem. 2014, 10, 767–773, doi:10.3762/bjoc.10.72

• -butyldimethylsilyl)]-β-cyclodextrin (50% in OV1701) as the stationary GC phase, operated at 100 °C. Under these conditions, the (2S,4S,6S)-enantiomer [30] is the later eluting stereoisomer, giving an α-value of (tr2:tr1) = 1.019 (see Supporting Information File 1, Figure S4). As a result of our investigations we

Synthesis of complex intermediates for the study of a dehydratase from borrelidin biosynthesis

• Frank Hahn,
• Nadine Kandziora,
• Steffen Friedrich and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 634–640, doi:10.3762/bjoc.10.55

• -unsaturated aldehyde 11 in a pure form. Synthesis of DH substrate surrogate For the synthesis of the DH substrate surrogate 5a we aimed at an anti-selective aldol reaction, which permits efficient access to the desired 2D,3D-stereoisomer followed by a smooth transformation into the SNAc thioester in the

Synthesis of new enantiopure poly(hydroxy)aminooxepanes as building blocks for multivalent carbohydrate mimetics

• Léa Bouché,
• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 213–223, doi:10.3762/bjoc.10.17

• -stereoisomer (with respect to C-3 of the 1,2-oxazine ring) was isolated after column chromatography. A product derived from the minor isomer of nitrone 3 was not detected and was apparently lost during the reaction or the purification. Since the stereogenic center of the 1,3-dioxolane ring is converted into an

The regioselective synthesis of spirooxindolo pyrrolidines and pyrrolizidines via three-component reactions of acrylamides and aroylacrylic acids with isatins and α-amino acids

• Tatyana L. Pavlovskaya,
• Fedor G. Yaremenko,
• Victoria V. Lipson,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Vladimir I. Musatov and
• Alexander S. Karpenko

Beilstein J. Org. Chem. 2014, 10, 117–126, doi:10.3762/bjoc.10.8

• the most reactive sites of the reagents. The reaction proceeds regioselectively with the addition of the most nucleophilic methylene group carbon of the azomethine ylide to the most electrophilic sites of the acrylamide and benzoylacrylic acid, which affords only one stereoisomer of cycloadducts 4 and

Plakilactones G and H from a marine sponge. Stereochemical determination of highly flexible systems by quantitative NMR-derived interproton distances combined with quantum mechanical calculations of ¹³C chemical shifts

• Simone Di Micco,
• Angela Zampella,
• Maria Valeria D’Auria,
• Carmen Festa,
• Simona De Marino,
• Raffaele Riccio,
• Craig P. Butts and
• Giuseppe Bifulco

Beilstein J. Org. Chem. 2013, 9, 2940–2949, doi:10.3762/bjoc.9.331

• coupling between vicinal protons H-15b–H-16 were chosen as the reference NOE for the 1D NOESY data set and the derived distance was adjusted for each stereoisomer in order to get the lowest MAE. To narrow the number of diastereoisomers, we initially analysed the relative configuration of C-7 and C-8, to

• polar and protic solvent such as methanol. Comparison of predicted 13C chemical shifts for 2a,b,e,f with the experimental values (Table 4) suggests the best fit with the experimental data for stereoisomer 2b. In particular, 2a presents a MAE more than twice the value found for 2b. The MAE of 2e is

• observed. The stereoisomer 2b shows all calculated 13C values falling in the proposed error limit of 2 ppm. For 2b, we observed a maximum error of 1.5 ppm. On the other hand, we found a |Δδ| of 2.5 ppm for 2f. Parallel with the MAE and |Δδ| analysis, we compared the calculated 13C chemical shifts with the

Total synthesis of the endogenous inflammation resolving lipid resolvin D2 using a common lynchpin

• John Li,
• May May Leong,
• Alastair Stewart and
• Mark A. Rizzacasa

Beilstein J. Org. Chem. 2013, 9, 2762–2766, doi:10.3762/bjoc.9.310

• stereoisomer analogues of RvD2 (1). Removal of the TIPS group with TBAF gave terminal alkyne 12. Alkyne 12 then underwent smooth hydrozirconation utilizing the procedure reported by Negishi [24] were ZrCp2HCl is generated in situ by reduction of ZrCp2Cl2 with DIBALH in THF. Iodinolysis of the zirconium species