Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• steric clashes or density effects). Another supporting finding can be seen in the fact that CSB (exhibiting iduronic acid in α-configuration, rather than its epimer, glucuronic acid, in β-configuration) showed virtually no binding to CMA1, further arguing for contacts of the GAG chain with the binding

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• group was introduced following the same method to produce PAF 4.15. By using the same methodology, the epimer of PAF 4.15 was synthesized. The group of Bittman reported in 1995 the synthesis of PAF with a four-step sequence starting from S-glycidol 5.1 in which the acylation of the sn-2 position was

Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr₄/PPh₃ and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

• Christian Schumacher,
• Jas S. Ward,
• Kari Rissanen,
• Carsten Bolm and
• Mohamed Ramadan El Sayed Aly

Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9

• refluxing toluene was reported to proceed with retention of configuration to afford the β-epimer 6 [16]. Another nice application of this chemistry was recently reported by Oestreich and co-workers, who converted 3β-hydroxypregn-5-en-20-one into the corresponding 3-bromo derivative, which also occurred with

• inversion. For note, the 1H NMR spectrum of 5 revealed the presence of ca. 15% of the β-epimer 6, which could result from an incomplete stereospecificity of the substitution opening an alternative reaction path. Also in this case, the NMR data are then in agreement with the reported ones [18]. In light of

• signal is attributed to the H-3 of (15%) byproduct 3β-azidocholest-5-ene; **denotes to two protons of the 3β-azidocholest-5-ene epimer [12]. Chemical structure of three isomeric cholesterols. Selected previously described cholesterol derivatives with interesting antibacterial and cytotoxic activities [9

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• alcohol on the A ring in 75% yield. The C3 epimer was also obtained in 4% yield and confirmed by X-ray diffraction. Hydrogenation of the sterically hindered C1–C2 alkene was accomplished using a combination of Mn(dpm)3 and Ph(iPrO)SiH2, providing grayanotoxin III in 51% yield. The authors also achieved

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• multigram scale, affording (−)-7-amino-7,8-dihydrobisabolene (4) and its C7-epimer as an 83:17 mixture of diastereomers in 87% overall yield. Unfortunately, these diastereomers were not separable by conventional column chromatography. Although this diastereomeric mixture could be converted into a variety of

• , we decided to prepare solid derivatives of 4 (and its C7-epimer) that could be purified by recrystallization. Although the α-bromoacetamide [10] and p-bromobenzamide derivatives of these amines are solids, no change in dr was observed upon recrystallization from a variety of solvents. Fortunately, we

• ultimately found success with the benzamide derivative 5, which could be prepared from the mixture of 4 and its C7-epimer in 93% yield upon treatment with benzoyl chloride. Recrystallization of the resulting mixture of diastereomeric amides from cyclohexane improved the dr from 83:17 to 95:5 (as determined

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• minor diastereoisomeric epimer in the phosphorus atom was also isolated in less than 8% yield (Scheme 23) [48]. The authors further performed detailed mechanistic investigations experimentally and theoretically [49][50]. Dinaphth-1-yl-N-alkyl-N-benzylphosphinamides 134 were also applied to the tandem

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• , respectively. In turn, the Gibbs energies of activation corresponding to the endo approaches indicate that cycloadduct 4 (ΔG‡1+2j->4-endo = 19.3 kcal/mol) is more kinetically favorable than its epimer 4' (ΔG‡1+2j->4'-endo = 20.3 kcal/mol). The small free energy difference (1.0 kcal/mol) between the two

The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban

• Martin Vrbický,
• Karel Macek,
• Jaroslav Pochobradský,
• Jan Svoboda,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2022, 18, 438–445, doi:10.3762/bjoc.18.46

• de were observed and the presence of the major S-enantiomer in the products 1 and 2 was confirmed by chiral HPLC analysis. Moreover, an enhancement of the abundance of the major epimer in the nitroaldols 22, 24, and 26 as well as the amides 27 and 28 was examined. Generally, epimers represent pairs

• ) values (83–90%) than in the previously published study (up to 72% ee) [13]. The introduction of a chiral moiety into the structure of aldehydes 16, 18 and 20 led to the formation of nitroaldols 22, 24, and 26 as pairs of epimers. Unfortunately, the attempts of separating the minor epimer were

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• the mixture of 38 and 39 induced a second α-ketol rearrangement to 40 as a tautomeric mixture. The same research group later utilized the same [3 + 2] cycloaddition and α-ketol rearrangement approach to prepare the 2′′′-epimer of 35, which bears an inverted methyl acetal in the dioxane ring, but this

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• depending on the type of underlying duplex, and these 4'-substituents were able to modulate the binding affinities for the parent 2'-modifed oligonucleotides [209]. siRNA containing inserts of the C4’ α-epimer of 2'-F,4'-OMe-rU, in either the sense or antisense strands, triggered gene silencing with

Fluorine effect in nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-D-hexopyranose

• Danny Lainé,
• Vincent Denavit,
• Olivier Lessard,
• Laurie Carrier,
• Charles-Émile Fecteau,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2020, 16, 2880–2887, doi:10.3762/bjoc.16.237

• reactions were monitored using 19F NMR spectroscopy with 2-fluoro-4-nitrotoluene as internal standard. Fluorodeoxygenation of glucopyranose 2 gave galactose 10 (inversion of configuration), as the only diastereoisomer (Table 1, entry 1). Interestingly, the epimer at C4 (compound 3) provided galactose 10

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• in a high yield and enantioselectivity (Scheme 5) [17][18]. The Rubottom oxidation [28] of 43 gave a separable mixture of the desired 44 and its C-14 epimer (≈7:1 ratio). The reductive deoxygenation of 44 proceeded via the tosylhydrazone to afford 45, which upon desilylation and alkyne isomerization

• 12c gave a separable mixture of the desired 49 (52%) along with the C-14 epimer (8%). More recently, the Ghosh group provided an alternative synthesis from the triacetyl ᴅ-glucal 60 (Scheme 8) [31]. The exhaustive hydrolysis and selective protection as the 4,6-O-di-tert-butylsilylene derivative 61 [32

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

• main product was crystallized and the configuration was determined by X-ray analysis proving the expected syn-configuration (compound 2-syn) [CCDC 1922520] (Figure 1). Epimer 2-syn was applied to Zemplén conditions prior to the ozonolysis. Conventional work-up, neutralization with acidic ion exchange

• further work up. This reaction mixture was cooled to −78 °C, purged with ozone for two minutes followed by reductive work-up employing triphenylphosphine which gave the corresponding glycosylated elongated aldoses 4-syn in full conversion as determined by TLC. Epimer 2-anti was reacted accordingly, after

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

• difficulty in extraction of 40 and 41 from the large quantity of alumina. Dehydration of the mixture of 40 and 41 in benzene quantitatively afforded a 1:2 mixture of 42 and its C-3 epimer 41. Reduction of the epimers with sodium borohydride and subsequent treatment with hydrochloric acid (2 N) gave single

• isomer 43. Treatment of 43 with methoxide ions in methanol at room temperature for 15 min gave the desired C-5 trans-butenolide 8 (40%) along with its C-5 cis-epimer 44 (60%), which is the sole product from the base-catalyzed isomerization of 43. Epoxidation of 43 gave a C-4,5-epoxide intermediate, which

• troublesome work (60% yield) due to the formation of the thermodynamic more stable C-5 cis-epimer 44 [66]. Thus, it may not be possible to obtain the desired triptophenolide methyl ether (8) in a satisfactory yield for a target-oriented synthesis. As the key structure element of various di- and triterpenes

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

• syntheses of this compound the general approach which employs the aziridine ester (2R,1'R)-5b as a starting material allows to also obtain its 5'-epimer and norfuranomycin (2S,2'R)-133 [87]. To construct the 2,5-dihydrofurane ring the aziridine alcohol (2R,1'R,1''R)-134 (Scheme 35) [88] was converted to the

• )-135 instead of the allyl residue opened the way to synthesis of ʟ-(+)-furanomycin and its 5'-epimer. MeBmt (2S,3R,4R,6E)-139 is a nonproteinogenic amino acid found as a constituent of the naturally occurring cyclic peptide cyclosporine currently in medical use as immunosuppressant [89]. Syntheses of

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

• the arabino-configurated epimer from the reaction mixture, which, if present, may therefore be formed in a very small amount. As expected, no regioisomer was detected, due to the contribution of both steric and electronic effects on the hydroboration at C-1 [7]. In order to explain the

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

• production and complexing properties [15]. Therefore, we decided to initially focus our genome mining efforts on the micacocidin-type cluster in Massilia sp. NR 4-1. Here, we report the outcome of this study, which led to the identification of a previously unrecognized agrochelin epimer and, furthermore

• S3, Supporting Information File 1). Conclusion In summary, Massilia sp. NR 4-1 was found to synthesize an epimer of the alkaloid agrochelin under iron-deficient conditions. The structure of massiliachelin is consistent with the architecture of a biosynthetic assembly line, which is encoded in the

Synthesis of non-racemic 4-nitro-2-sulfonylbutan-1-ones via Ni(II)-catalyzed asymmetric Michael reaction of β-ketosulfones

• Alexander N. Reznikov,
• Anastasiya E. Sibiryakova,
• Marat R. Baimuratov,
• Eugene V. Golovin,
• Victor B. Rybakov and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2019, 15, 1289–1297, doi:10.3762/bjoc.15.127

• more rapid than the epimerization of product 8a. After about 60 hours the content of sulfone 5a in solution became almost constant, while the amount of epimer 9a continued to increase. This fact may indicate that the formation of compound 9a may occur not only as a result of keto–enol tautomerism in

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

• , but with the tetrahydropyrane ring having α orientation. A mixture of epimers at position 4' was also obtained when using the C-5 epimer of substrate 33. Asif et al. [36] developed another 3CR for the synthesis of steroidal thiazole derivatives. As shown in Scheme 11, cholestanic ketone 7 was reacted

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

• ) 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

Pd-Catalyzed microwave-assisted synthesis of phosphonated 13α-estrones as potential OATP2B1, 17β-HSD1 and/or STS inhibitors

• Rebeka Jójárt,
• Szabolcs Pécsy,
• György Keglevich,
• Mihály Szécsi,
• Réka Rigó,
• Csilla Özvegy-Laczka,
• Gábor Kecskeméti and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 2838–2845, doi:10.3762/bjoc.14.262

• -sulfate uptake by OATP2B1 [6]. None of the steroidal STS or 17β-HSD1 inhibitors reached the clinical trial, which is mainly due to their retained estrogenic activity. This side-effect could be eliminated by the inhibitor design based on the 13-epimer of natural estrone (13α-estrone, 13αE1OH) [17][18

• ]. Poirier et al. proved that 13α-derivatives of 3,17-estradiols have reduced binding affinity for estrogen receptor alpha and display no uterotropic activity [19]. The conformational change resulting from the inversion at C-13 leads to an epimer unable to bind to its nuclear receptors. We have recently

Synthesis of cis-hydrindan-2,4-diones bearing an all-carbon quaternary center by a Danheiser annulation

• Gisela V. Saborit,
• Carlos Cativiela,
• Ana I. Jiménez,
• Josep Bonjoch and
• Ben Bradshaw

Beilstein J. Org. Chem. 2018, 14, 2597–2601, doi:10.3762/bjoc.14.237

• relative configuration of the major epimer of 8 (Figure 3) was established on the basis of a cross peak in the NOESY spectrum that correlated the methyl group at C3 with a methylene proton adjacent to the quaternary carbon of the side chain at C3a. The configuration at C3, adjacent to a carbonyl group, is

Synthesis of eunicellane-type bicycles embedding a 1,3-cyclohexadiene moiety

• Alex Frichert,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2018, 14, 2461–2467, doi:10.3762/bjoc.14.222

• diastereoselectivity, which means that every single example has to be explored independently. The assignment of the configuration and preferred conformation of product 18 was conducted on the basis of NOESY NMR experiments. Our analysis was aided by the observation that the 2-epimer 19 was accessible by oxidation of

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• performed using “odorless” thioglycoside 155 and 149 as the donor and the acceptor [81]. Even with the combination of “disarmed” 155 and “armed” 149, the reaction gave rise to the desired disaccharide 157 in 87% yield. The same reaction of the corresponding 3-epimer 156 proceeded smoothly to give the