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

• product is then reacted with unprotected thymine which, in the presence of stoichiometric amounts of sodium hydride, results in the epoxide ring opening and the formation of the glycol backbone. The pre-amidite is then phosphitylated yielding the desired GNA-T amidite (Scheme 3). Recently, this simple

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

Stereoselective syntheses of 3-aminocyclooctanetriols and halocyclooctanetriols

• Emine Salamci and
• Yunus Zozik

Beilstein J. Org. Chem. 2021, 17, 705–710, doi:10.3762/bjoc.17.59

• should have a cis configuration relative to the protons H-3 and H-4. Next, the reduction of azidotriol 10 by hydrogenation afforded the target aminotriol 12 in 95% yield. For the synthesis of the other aminocyclooctanetriol 18, the diol 6a [33] was reacted with m-CPBA to give trans-epoxide isomer 13 [33

• ] (79% yield) as the sole product (Scheme 3). Ring opening of trans-epoxide 13 by HBr(g)–MeOH gave bromotriol 14, which is an ideal substrate for the synthesis of the aminocyclooctanetriol 18. For structural proof, bromotriol 14 was converted into the corresponding acetate 15 using Ac2O in pyridine and

• synthesis of chlorocyclooctanetriol 19 starting from the trans-epoxide 13 (Scheme 4). The hydroxy groups in 19 were acetylated to give 20 for further characterization of the structure. The position of the chlorine atom in 20 was confirmed with the help of the COSY spectra. The resonance signal of H-3

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• cyclizations to lactams of type 10 based on the persistent radical effect (PRE) are unknown and may provide a simple access to 3,4-disubstituted γ-lactams. We report here that tandem nucleophilic epoxide ring-opening/Brook rearrangement/radical oxygenation reactions are indeed very effective for the synthesis

• enantiomerically pure epoxides (S)-7b, (R)-7b, or (S)-7e (Table 2, entries 8–12) at 0 °C. The epoxide opening/Brook rearrangement steps were typically complete after an hour, except for cyclohexene oxide 7f for which the nucleophilic opening and Brook rearrangement steps took 24 h (Table 2, entry 13). Ferrocenium

• hexafluorophosphate (4) and TEMPO (3) were subsequently added to trigger the single electron oxidation of the formed amide enolates and radical oxygenation affording α-(aminoxy)amides 9a–n in good 51–77% isolated yields. Cyclic units in the allylic N-substituent (Table 2, entries 14 and 15) and the epoxide (Table 2

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

• a variety of alkenes as an interesting heterogeneous system. This cobalt oxide mesoporous nanomaterial showed good activity and selectivity to the epoxide product and could be recovered and reused, but the multistep (not straightforward) synthesis of the catalyst and the use of DMF as the solvent

• (Table 1, entries 1–4), only the CoNPs/MgO catalyst gave a modest 28% conversion to the desired epoxide 2a (Table 1, entry 2) together with undesired formamide byproducts, probably coming from DMF decomposition under the reaction conditions. Then, we decided to use acetontrile (MeCN) as the solvent with

• poorer conversions and selectivities (Table 1, entries 11 and 12). Next, we worked on the optimization of the catalyst loading. Thus, when the amount of catalyst was decreased from 50 mg to 20 mg, a higher conversion was observed along with a slight drop in the selectivity towards the epoxide product 2a

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• , was also reported in 1980 [10]. Following a 23-year hiatus, two papers submitted within two weeks of each other reported, respectively: (1) the isolation from Streptomyces sp. UMA-044 and characterization of NP25302, that differs from bohemamine in lacking the 6,7-epoxide functionality [11] and (2

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

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• -workers in 2014 [49] (Scheme 9A). The synthesis began with the conversion of ketone 112 into alcohol 113 in four steps, which involved a hypervalent iodine-mediated ring expansion [60]. A two-step synthesis from 113 gave epoxide 114. Epoxide 114 was converted to the corresponding β-ketoester and

Easy access to a carbohydrate-based template for stimuli-responsive surfactants

• Thomas Holmstrøm,
• Daniel Raydan and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2020, 16, 2788–2794, doi:10.3762/bjoc.16.229

• with high regioselectivity via the Černý epoxide [20]. Results and Discussion Synthesis The synthesis was initiated by a regioselective esterification of levoglucosan (1) with tosyl chloride in pyridine, first presented by Černý and co-workers, in order to afford the 1,6-anhydro-2,4-di-O-tosyl-β-ᴅ

• -glucopyranose as an intermediate. The latter could be used in the next step upon concentration of the reaction mixture under reduced pressure (Scheme 1) [20]. The intermediate was then treated with sodium methoxide in the presence of pyridine in order to generate the Černý epoxide 2 in a 73% yield over two

• steps [20]. Subjecting the Černý epoxide to sodium azide at an elevated temperature in a mixture of DMF and water afforded the diazide 3 in a 76% yield [21][22]. The presence of the azido groups was supported by a band at ≈2100 cm−1 in the FTIR spectrum of the diazide 3. The 1,6-anydro functionality

3-Acetoxy-fatty acid isoprenyl esters from androconia of the ithomiine butterfly Ithomia salapia

• Florian Mann,
• Daiane Szczerbowski,
• Lisa de Silva,
• Melanie McClure,
• Marianne Elias and
• Stefan Schulz

Beilstein J. Org. Chem. 2020, 16, 2776–2787, doi:10.3762/bjoc.16.228

• -enoate (12) was performed to verify the structural proposal and to determine the absolute configuration of the natural product (Scheme 4). The commercially available epoxide (S)-22 served as chiral starting material. 1,9-Nonanediol (19) was monobrominated and oxidized with IBX to yield 9-bromononanal (20

• ). A Wittig reaction with pentylphosphonium bromide resulted in bromoalkene 21 in a 9:1 Z/E-mixture. In the following step, the Grignard reagent of 21 was converted into the respective Gilman cuprate with Cu(I)I for the selective reaction with the epoxide function of (S)-22 [34]. The hydroxyester 23

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

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

• oxidation stereoselectively generated the spirocyclic epoxide 76. A second-protecting group shuffle afforded the primary alcohol 77. A Mitsunobu substitution of 77 with 2-mercaptobenzothiazole, followed by an oxidation with a large excess of mCPBA afforded the sulfone 78. While not producing the identical

• removal of the dithiane protecting group and the cyclic-ketal formation gave 84. The oxidative hydrolysis of the PMB ether and the reaction with mCPBA afforded the epoxide 85. While relatively short (9 steps), the nonstereoselective formation of 81a/b led to a lower overall yield. Syntheses of the C-1–C-6

• exocyclic epoxide prior to the formation of the C-6–C-9 conjugated diene was necessary in order to avoid the unwanted epoxidation of the C-6–C-7 olefin. Koide employed a unique strategy in which the exocyclic epoxide was generated as the initial stereocenter (Scheme 15) [12][13]. The Sharpless asymmetric

One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: theoretical evidence for an asynchronous concerted pathway

• Esra Demir,
• Ozlem Sari,
• Yasin Çetinkaya,
• Ufuk Atmaca,
• Safiye Sağ Erdem and
• Murat Çelik

Beilstein J. Org. Chem. 2020, 16, 1805–1819, doi:10.3762/bjoc.16.148

• natural products ranging from small molecules, such as sugars, lipids and amino acids to huge molecules [56]. Computational results A detailed mechanistic investigation of the synthesis of oxazolidinone and five-membered cyclic carbonate derivatives by the reaction between epoxide 7f and CSI has been

• performed. Formation of oxazolidinone 9f There are two possible channels for the cyclization reaction of epoxide 7f with CSI to form oxazolidinone intermediates 10 and 11 as shown in Figure 1. In both transition states it is found that the ring-opening reaction of the epoxide, a nucleophilic attack of N4

• N4 onto the less sterically encumbered C1 atom of the epoxide 7f forming intermediate 11. Optimized geometries of transition structures are depicted in Figure 1. Our calculated results for the reaction indicate 17.4 kcal/mol (gas phase) and 26.7 kcal/mol (in DCM) preference for the TS1 over the TS1

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• , cyclopentanone, and three carbon ring-expanded 1,3-diones from vinyl spiro epoxides [14]. The reaction is initiated by the addition of a thiyl radical to the vinyl epoxide 24, followed by the epoxide fragmentation to the alkoxy radical 25. Then, the β-cleavage to form the carbon-centered radical 26, the final

Recent synthesis of thietanes

• Jiaxi Xu

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

The charge-assisted hydrogen-bonded organic framework (CAHOF) self-assembled from the conjugated acid of tetrakis(4-aminophenyl)methane and 2,6-naphthalenedisulfonate as a new class of recyclable Brønsted acid catalysts

• Svetlana A. Kuznetsova,
• Alexander S. Gak,
• Yulia V. Nelyubina,
• Vladimir A. Larionov,
• Han Li,
• Michael North,
• Vladimir P. Zhereb,
• Alexander F. Smol'yakov,
• Artem O. Dmitrienko,
• Michael G. Medvedev,
• Igor S. Gerasimov,
• Ashot S. Saghyan and
• Yuri N. Belokon

Beilstein J. Org. Chem. 2020, 16, 1124–1134, doi:10.3762/bjoc.16.99

• , providing some dissolved F-1 as the real catalyst. In all cases, the catalyst could easily be recovered and recycled. Keywords: Brønsted acid catalyst; charge-assisted hydrogen-bonded framework; Diels–Alder; epoxide ring opening; heterogeneous catalyst; Introduction Tremendous successes in homogeneous

• applications of the material. Thus, the catalytic properties of uncrystallized F-1 and F-1 with an F-1a phase were explored in a series of reactions typically promoted by Brønsted acids, such as epoxide ring openings with methanol and water (Scheme 2). The reactions were conducted at room temperature, and

• mixture was catalytically inactive, and after 24 hours, the reaction contained the epoxide 2 and traces of 3 (less than 1% yield, Table 1, run 6). This observation clearly showed that dissolved (leached) parts of F-1, even if present, could not be responsible for the catalytic performance. To investigate

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• cycloaddition, an epoxidation, and a biomimetic epoxide opening. Synthesis of (−)-amphidinolide E (3) using an intermolecular enyne metathesis as the key step. Synthesis of amphidinolide K (4) by an enyne metathesis route. Trost synthesis of des-epoxy-amphidinolide N (5) [72]. Enyne metathesis between the

Synthesis of disparlure and monachalure enantiomers from 2,3-butanediacetals

• Adam Drop,
• Hubert Wojtasek and
• Bożena Frąckowiak-Wojtasek

Beilstein J. Org. Chem. 2020, 16, 616–620, doi:10.3762/bjoc.16.57

• -5,6-dimethyl-1,4-dioxane-2-carboxylate as the starting material. Keywords: 2,3-butanediacetal; cis-epoxide; (−)-disparlure; (+)-disparlure; (−)-monachalure; (+)-monachalure; Introduction Compounds containing chiral epoxides display a wide range of biological activities and a number of them are

• , giving compounds 22 and 23. The butanediacetal groups were then removed with p-toluenesulfonic acid and diols 5 and 6 were obtained with 79% and 64% yield, respectively. They were then used in a well-established three-step, one-pot procedure for epoxide ring closure [26][30][40][41]. Pure (+)-disparlure

Photophysics and photochemistry of NIR absorbers derived from cyanines: key to new technologies based on chemistry 4.0

• Bernd Strehmel,
• Christian Schmitz,
• Ceren Kütahya,
• Yulian Pang,
• Anke Drewitz and
• Heinz Mustroph

Beilstein J. Org. Chem. 2020, 16, 415–444, doi:10.3762/bjoc.16.40

• photopolymerization with cyanine as sensitizers combined with 88 as PF6−-salt. Exposure with a high power NIR LED emitting at 805 nm initiated cationic photopolymerization of the epoxide Epikote 357, Figure 3. Decomposition of the oxidized sensitizer/oxidized photoactive compound PA+• (Equation 7) provided the

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• sesquiterpenes (type I TCs), diterpenes can either be generated by type I TCs or type II TCs [11][55]. Type II TCs initiate carbocation formation by Brønsted acid catalysis to protonate a terminal isoprene double bond or an epoxide ring (Figure 5b) [56]. Thus, cyclization mediated by type II TCs leads to an

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

• -small cell lung cancer with ED50 values of 6.5 and 16.7 µg mL−1, respectively [71]. To obtain this interesting compound isolated from Dictyota dichotoma, C14 has to be modified with a keto function and the double bond between C3 and C4 has to be converted into an epoxide. Additionally, 3,7,18

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

• singlet state oxygen to form similar peroxide, epoxide or epidioxide [16] derivatives, which can be isolated at room temperature (Scheme 4). An interesting physical characteristic of pentafulvene derivatives is their bright colour, which results from their cross conjugation, and varies with substitution

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

• C19H24O5 for the first compound, which was supported by the 13C spectrum (Table 1). By comparing the spectrum to NMR data of other withanolides, we quickly identified the Michael system in ring A based on two olefinic protons (δH 6.94 and 6.22 ppm), a secondary alcohol at C-4 (δH 3.79 ppm), a 5,6-epoxide

• formula of C19H24O3 based on HRESIMS and 13C NMR (Table 1). In contrast to the first compound, no epoxide and no secondary alcohol at C-4 was present, in agreement with the different elemental composition. Instead, 13C NMR indicated a double bond at C5–C6 (δC 135.7 and 124.3 ppm). Otherwise, all spin

• -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

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

• 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

• isomerization of olefin 43, the benzylic oxidation of 8, the use of m-CPBA to introduce the C-9,11 epoxide and the non-stereoselective reduction of the C-14 carbonyl group using sodium borohydride, caused an unacceptable overall yield (1.6%). This pioneering work undoubtedly established the basis for the future

• epoxide as a single diastereomer via in situ-generated methyl(trifluoromethyl)dioxirane and the reduction of the C-14 ketone in the presence of Eu(fod)3 to give triptolide (47%) together with its C-14 α-hydroxy epimer epi-triptolide (47%). In 2014, Li’s group reported a divergent synthesis for triptolide

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

• acids and their cyclic forms (pyrrolidin-2-ones) takes advantage of the stereoselective epoxidation of the aziridine acrylaldehyde 161 to predominantly (98:2) form the aziridine epoxide 162 when (S)-[diphenyl(trimethylsilyloxy)methyl]pyrrolidine was used as a catalyst (Scheme 42) [94]. A key β

• -hydroxyester 163 was produced from the epoxide 162 employing N-heterocyclic carbene catalysis. Openings of the aziridine ring in 163a with azide or in 163b with in acetic acid provided enantiomerically pure methyl (3S,4S)-4,5-di-N-Boc-amino-3-hydroxypentanoate 164 or 4-N-Boc-amino-3,5-dihydroxypentanoate 165

• as components of a variety of plants and exhibit a wide range of biological properties including inhibition of glucosidases [102]. When the aziridine epoxide 162 was treated with acetic acid the aziridine ring cleavage was observed to give the epoxyaldehyde 178 (Scheme 45) [94]. Catalytic

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

• derivatisation method that uses low-boiling epoxide reagents in a high-energy ball mill (HEBM). The simplified preparation and purification of low substitution-degree common (2-hydroxy)propylated β- and γ-cyclodextrins (β/γ-CDs) has been realised. The intelligent use of propylene oxide has also facilitated the

• is that the first step produces CD-propyl chlorohydrin, which is immediately transformed into an epoxide that can either react with other CDs, to form CDP, or with a hydroxy ion, to produce a (2,3-dihydroxy)propyl side chain. The hydrolytic reaction is unavoidable because of the aqueous solution and

• reagent, which can occur either via hydrolysis by the residual water or escape via evaporation, the jar was cooled with liquid N2 below −30 °C after the sodium salt formation of the CDs and before the epoxide was added to the light, electrostatic powder. Liquid N2 not only worked as a cooling medium, but