Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• the steroidal family of spirostans and three-membered spiro heterocyclic steroids, as oxirane derivatives are typically prepared to expand into four- or more membered rings rather than being the final target. The described methodologies are presented to facilitate the identification of the atoms or

• ]oxazinan)-6'-one derivatives with two types of molecular diversity as part of their efforts to produce inhibitors of 17β-HSDs [61]. The first type of diversity was achieved by introducing different amino acids through the opening of the oxirane ring on compound 127. After lactonization of compounds 128

• as a 17β-HSD3 inhibitor [42]. The same research group reported a new family of 3-spiromorpholinones derived from ADT bearing hydrophobic substituents [43][62]. The synthetic key step involved a regioselective aminolysis of the oxirane 131 with different ʟ- or ᴅ-amino acids (53–99% yields) to obtain

(E,Z)-1,1,1,4,4,4-Hexafluorobut-2-enes: hydrofluoroolefins halogenation/dehydrohalogenation cascade to reach new fluorinated allene

• Nataliia V. Kirij,
• Andrey A. Filatov,
• Yurii L. Yagupolskii,
• Sheng Peng and
• Lee Sprague

Beilstein J. Org. Chem. 2024, 20, 452–459, doi:10.3762/bjoc.20.40

• oxirane [14]. A related study has demonstrated that (E)-butene 1a reacts with potassium persulfate to form 4,5-bistrifluoromethyl)-1,3,2-dioxathiolane 2,2-dioxide [15]. In 2021 Petrov published an article on the interaction of fluorinated olefins with fluorinated thioketones. In this publication it was

A study of the photochemical behavior of terarylenes containing allomaltol and pyrazole fragments

• Constantine V. Milyutin,
• Andrey N. Komogortsev,
• Boris V. Lichitsky and
• Valeriya G. Melekhina

Beilstein J. Org. Chem. 2022, 18, 588–596, doi:10.3762/bjoc.18.61

• proton transfer (ESIPT) [34][35][36]. At first, compound 12a under UV irradiation undergoes rapid proton transfer from the excited state A* resulting in the formation of photoisomer B* followed by the conversion to intermediate C. Further transformation of zwitter-ion C to bicyclic oxirane D and its

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

• İlknur Polat,
• Selçuk Eşsiz,
• Uğur Bozkaya and
• Emine Salamci

Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7

• cyclic β-amino acid derivative, was achieved by oxirane ring opening in epoxide 7 with HCl(g)–MeOH, NaHSO4, or NH4Cl–DMF. The regioselectivity of oxirane ring-opening in 7 was attributed to the conformational effects. The mechanism for the formation of compound 10 was elucidated with DFT computations

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• compound 82. This molecule is expected to be available from cross metathesis of olefins 83 and 84. These two intermediates can then be readily prepared from optically active oxirane 85 and its enantiomer which can be derived through the Sharpless epoxidation of penta-1,4-dien-3-ol (86). In the synthesis

• epoxidation protocol was applied to the double bond using (−)-DET to afford chiral oxirane 100 in 85% yield. The free primary alcohol was then protected as tosyl ester 101 and treated with p-TSA to induce intramolecular cyclization. The anticipated furan 95 was successfully isolated in 85% accompanied with

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• opening attempt of chiral oxirane 153 in the presence of BF3.Et2O (Scheme 20) [104]. The synthetic route to the desired product was smoothly brought to its course by employing CuCN in the medium. Amines The enzymes indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) are responsible

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

A new and efficient methodology for olefin epoxidation catalyzed by supported cobalt nanoparticles

• Lucía Rossi-Fernández,
• Viviana Dorn and
• Gabriel Radivoy

Beilstein J. Org. Chem. 2021, 17, 519–526, doi:10.3762/bjoc.17.46

• because they are present in many important (bio)organic compounds and also allow access to more functionalized or complex structures through different chemical transformations on the reactive oxirane ring [2][3][4][5][6][7][8][9][10][11][12]. Despite many methodologies for the synthesis of epoxides have

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• yields were best in the reactions with electron-rich alkenes and when a low concentration of the base was used to minimize the destruction of difluorocarbene. The use of oxirane or epichlorohydrin as hydrogen halide scavengers avoided the need for a stoichiometric amount of the strong base [16][17]. The

• opening of the oxirane ring by bromide ions under homogeneous conditions generated a bromoalkoxide ion which then acted as the base, leading to cyclopropanes 4 and 6 (Scheme 2). However, the harsh conditions needed (high temperatures, autoclave) limited the approach. In the case of electron-rich alkenes

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

• (the C2–F2 bond is antiperiplanar to the C3–C4 bond) [37]. As a result, the oxiranium ion could be stabilized in the presence of triethylamine. A lone pair of electrons on the nitrogen atom from triethylamine overlaps with the antibonding σ* orbital of the O5–C4 bond of the oxirane, favoring the

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

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

• 100 was relatively inefficient (31%) and was the main factor in diminishing the overall yield. The transformation of the silyl-protected 1° alcohol group of 100 into an ester afforded 101. Finally, the C-3 spirocyclic oxirane was introduced stereoselectively by a VO(acac)2-directed epoxidation. While

• 110. In a fashion similar to that used by Ghosh’s group, the VO(acac)2-catalyzed epoxidation of 110 afforded the spirocyclic oxirane 111. A subsequent ring opening with LiCl gave 112, which was used in the synthesis of thailanstatin B (5). Nicolaou’s route to 111 (9 steps, 29.9% yield) is shorter and

• , followed by a transmetalation provided a vinylzinc reagent that was coupled with 48 to afford 128, for which only the E-stereoisomer was observed. Notably, the Negishi conditions were tolerant to the azide present in 48 and the oxirane and 1° iodoalkane present in 91. The subsequent reduction of the azide

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• was first converted to the oxirane-fused derivative 98 through an intramolecular substitution. After hydrolysis, the thiolate underwent an intramolecular nucleophilic displacement to generate the final thietane-fused α-D-gulopyranoside 100 [50] (Scheme 21). In 2004, Schulze and co-workers synthesized

• converted into 3,5-anhydro-3-thiopentofuranosides 135 through a Mitsunobu reaction with thiolacetic acid and hydrolysis followed by an intramolecular nucleophilic ring-opening of the oxirane ring. The newly generated thiolate underwent a nucleophilic ring-opening of the oxirane to generate the thietane ring

• in the presence of Ba(OH)2 to give the corresponding thietane-3-ols 145. In this reaction H2S first was deprotonated to the hydrogensulfide anion (−SH) by Ba(OH)2. The obtained anion nucleophilically attacked the less steric or benzylic ring carbon atom of the oxirane ring, giving mercaptoalkanolates

Reaction of oxiranes with cyclodextrins under high-energy ball-milling conditions

• László Jicsinszky,
• Federica Calsolaro,
• Katia Martina,
• Fabio Bucciol,
• Maela Manzoli and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2019, 15, 1448–1459, doi:10.3762/bjoc.15.145

• , depending on the molar ratio of the CD and epichlorohydrin [40][41][42][43]. As in the HPCD preparations, the aqueous basic solution can crosslink the macrocycles, while the relatively large OH− excess can hydrolyse both the reagent and the simultaneously formed oxirane. In order to prepare bead CDPs

• were found between the products that were prepared from the dried and hydrated CDs. (3-Glycidyloxypropyl)trimethoxysilane (GPTS) The hydrolysis of GPTS occurs at two sites; on the oxirane ring and on the silyl ether moiety. The cleavage of trimethoxysilyl ether is unavoidable in the aqueous phase under

• basic conditions, while the oxirane ring seems to be more stable than in propylene oxide or epichlorohydrin. This is partially the consequence of its considerably lower aqueous solubility. It was found that the substitution reaction does not proceed, or at least does so very slow at temperatures below

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

• -coupling reactions. Herein, stereodefined 1,3-enynes, including tetrasubstituted ones, were straightforwardly synthesized from cis or trans-alkynylated oxiranes in good to excellent yields by a one-pot cascade process. The procedure relies on oxirane deprotonation, borylation and a stereospecific

• 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

• relationship between the starting oxirane and the enyne product was always obtained, whatever the group transferred from boron to the oxirane carbon. These results revealed the stereospecificity of the reaction and suggested that no epimerization of the oxiranyllithium intermediate occurred. The present

Synthesis of acylglycerol derivatives by mechanochemistry

• Karen J. Ardila-Fierro,
• Andrij Pich,
• Marc Spehr,
• José G. Hernández and
• Carsten Bolm

Beilstein J. Org. Chem. 2019, 15, 811–817, doi:10.3762/bjoc.15.78

• stearic acid (3a) in the presence of amines such as pyridine or tributylamine. However, the analysis of the reaction mixture only showed unreacted starting materials. In previous work, an acceleration of the oxirane ring-opening reaction with carboxylic acids [34] or alcohols [35] by using Lewis acid

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• (Scheme 11) [60]. Sharpless epoxidation of the allylic alcohol 48 gave a 46:11:33 mixture of (S)-48, (3R,4S)-49 and (2R,3R)-50. While (S)-48 is a product of kinetic resolution, the formation of (2R,3R)-50 results from the intramolecular opening of the oxirane ring in (3R,4S)-49. After chromatographic

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

• fluorination conditions. In a former investigation on oxirane opening reactions of various epoxycycloalkane β-aminocarboxylates [27], a high substrate dependence and directing effect of the functional groups has been observed. These results led us to perform similar investigations with the above mentioned

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

• aromatic systems. Miscellaneous reactions The oxidation of E-1a with H2O2 in acetonitrile gave oxirane 101, which subsequently was used for reactions with diverse nucleophiles [80] (Scheme 32). Upon treatment with diheptyl sulfide, 101 was transformed into ethoxalyl cyanide (102) [81]. The aziridination of

• ). Formation of disulfides through reaction of thiols with E-1a. Formation of CT salts of E-1 with Mn2+ and Cr2+ metallocenes through one-electron transfer. Oxidation of diethyl dicyanofumarate (E-1a) with H2O2 to give oxirane 101. The aziridination of E-1b through nitrene addition. Acknowledgements The

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

• diastereoisomeric lactone 52 in 76% yield. This lactone (52) was converted to enediol 53 in a further few steps. The second THF ring was then established using an epoxidation–cyclization sequence. Thus, asymmetric Sharpless epoxidation (SAE) [103][104] yielded an intermediary oxirane (not shown in Scheme 12) which

Synthesis of the C8’-epimeric thymine pyranosyl amino acid core of amipurimycin

• Pramod R. Markad,
• Navanath Kumbhar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2016, 12, 1765–1771, doi:10.3762/bjoc.12.165

• -glucose derived alcohol 3 in 13 steps and 14% overall yield. Thus, the Sharpless asymmetric epoxidation of allyl alcohol 7 followed by trimethyl borate mediated regio-selective oxirane ring opening with azide, afforded azido diol 10. The acid-catalyzed 1,2-acetonide ring opening in 10 concomitantly led to

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

• Štěpán Horník,
• Lucie Červenková Šťastná,
• Petra Cuřínová,
• Jan Sýkora,
• Kateřina Káňová,
• Roman Hrstka,
• Ivana Císařová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2016, 12, 750–759, doi:10.3762/bjoc.12.75

• ] of 14 followed by azidolysis [41] furnished 15. 2-Azido-3,4-epoxide 18 was prepared from readily available [42] 2,3-isopropylidene-D-mannosan (16) in five steps (Scheme 2). Tosylation of 16 [43], followed by hydrolysis of the benzylidene acetal [44] and oxirane ring closure [45] at C-4 delivered 1,6

• inversion at C-4 giving 3,4-difluoro analog 22. The D-galacto configuration of 22 was manifested by the values of the vicinal coupling constants 3JH2,H3 = 1.6 Hz and 3JH3,H4 = 4.5 Hz, and the large value of 2JC5,F4 = 27.2 Hz confirmed the equatorial position of fluorine at C-4. Cleavage of the oxirane ring

• ]. Azidolysis of the oxirane ring in the reaction with lithium azide furnished 2-azido derivative 31. Although nucleophilic cleavage of a three-membered ring annulated to the 1,6-anhydrohexopyranose skeleton usually occurs solely in trans-diaxial fashion [50], formation of the trans-diequatorial side-product 32

Highly stable and reusable immobilized formate dehydrogenases: Promising biocatalysts for in situ regeneration of NADH

• Barış Binay,
• Dilek Alagöz,
• Deniz Yildirim,
• Ayhan Çelik and
• S. Seyhan Tükel

Beilstein J. Org. Chem. 2016, 12, 271–277, doi:10.3762/bjoc.12.29

• Jersey, USA). Sodium formate, Immobead 150 (Polyacrylic matrix, particle size 250 μm, oxirane content ≥200 μmol/g dry support), ethylenediamine (EDA), glutaraldehyde and sodium metaperiodate were obtained from Sigma-Aldrich (St. Louis, MO, USA). All other chemicals used in this study were of analytical

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• . This surprising result contradicts an elimination mechanism in the formation of 70 and demands for a new mechanistic proposal. Alternatively, an intramolecular attack at C-3 by the neighbouring hydroxy group at C-4 to cleave the activated pyruvate via an oxirane intermediate can be thought of. To test

• this hypothesis, chorismate with an 18O label in its hydroxy function was prepared enzymatically starting from isochorismate. This label was retained during the reaction supporting the oxirane intermediate. The mechanism was also proposed for the XanB2-subfamily, which shows an unselective opening of

• the oxirane ring to produce both 70 and 4-hydroxybenzoate (71). This study created an interesting example of 18O usage to distinguish two different mechanisms of action within the same family of enzymes. Due to the poor availability of isotopically labeled sulfur compounds, corresponding labeling

The chemical behavior of terminally tert-butylated polyolefins

• Dagmar Klein,
• Henning Hopf,
• Peter G. Jones,
• Ina Dix and
• Ralf Hänel

Beilstein J. Org. Chem. 2015, 11, 1246–1258, doi:10.3762/bjoc.11.139

• rearrangement followed by deprotonation. Under non-acidic conditions, this process would not be expected; and indeed, when 7 was oxidized with dimethyldioxirane (DMDO) in acetone at room temperature, epoxide 32 with a central oxirane ring is produced in acceptable yield (59%). Since we were unable to obtain

• δ = 161 ppm, whereas the –CH= carbon atoms absorb at 122 ppm. The oxirane carbon atoms appear at 59 ppm. When the double bond chain is extended by one –CH=CH– group, results were obtained comparable to those observed for 7 (Scheme 8). Thus, tetraene 19 yielded mono-epoxide 33 with MCPBA in

Indolizines and pyrrolo[1,2-c]pyrimidines decorated with a pyrimidine and a pyridine unit respectively

• Marcel Mirel Popa,
• Emilian Georgescu,
• Mino R. Caira,
• Florentina Georgescu,
• Constantin Draghici,
• Raluca Stan,
• Calin Deleanu and
• Florea Dumitrascu

Beilstein J. Org. Chem. 2015, 11, 1079–1088, doi:10.3762/bjoc.11.121

• 17 on the oxirane ring in the 1,2-epoxybutane (Scheme 4). The reactive intermediate obtained by the ring opening of the 1,2-epoxybutane abstracts a methylene proton from the salt, generating the corresponding N-ylide (18) in situ. The N-ylide reacts further with the acetylenic dipolarophile to give a