Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99

• reaction of phenacyl bromide, malononitrile, dialkyl but-2-ynedioate, and triphenylphosphine has been already reported, in which diethyl 3-phenyl-5,5-dicyanocyclopent-2-ene-1,2-dicarboxylates were produced by further elimination of a hydroxy group [30]. In the present reaction, the hydroxy group is still

• displayed a singlet at 3.52 ppm for the hydroxy group and two singlets at 3.24, 3.96 ppm with J = 14.8 Hz for the two diastereotopic protons of the cyclic methylene unit. The single crystal structure of compound 3k was successfully determined by X-ray diffraction analysis (Figure 1). From Figure 1, it can

• be seen that the C–C double bond is connected to two methoxycarbonyl groups. Though one hydroxy group exists on the reactive allyl position and benzyl position, it still is present in the molecule and did not give the cyclopentadiene by further elimination of water. In order to obtain the

Synthesis and HDAC inhibitory activity of pyrimidine-based hydroxamic acids

• Virginija Jakubkiene,
• Gabrielius Ernis Valiulis,
• Markus Schweipert,
• Asta Zubriene,
• Daumantas Matulis,
• Franz-Josef Meyer-Almes and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 837–844, doi:10.3762/bjoc.18.84

• gave the corresponding (2-substituted pyrimidin-4-yloxy)acetates 6–9. In order to replace the 2-methylsulfonyl group with a hydroxy group, we tested several techniques. It was found that heating compound 5 with water in dimethyl sulfoxide at 100 °C or boiling for 1 h in water led to hydrolysis of both

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• product. The functional analysis of FtmOx1 indicated that the enzyme accepts fumitremorgin B as a substrate and catalyzes the formation of verruculogen and a C13-oxo product, through the installation of an endoperoxide bridge between C21 and C27 of fumitremorgin B and oxidation of the C13-hydroxy group of

• endoperoxide with a C26 radical intermediate. Finally, the radical is quenched by hydrogen atom donation from Tyr224, to form verruculogen and a tyrosyl radical for the next round of the reaction. The tyrosyl radical at Tyr224 is also involved in the oxidation of the C13-hydroxy group of verruculogen to a C13

• located on the protein surface and solvent-exposed, the distance between C21 of fumitremorgin B and the iron center is 4.6 Å and the hydroxy group of Tyr68 is near C26 of fumitremorgin B (Figure 3C). Moreover, Tyr68 is located close to C13 of fumitremorgin B, at a distance of 3.7 Å. The comparison between

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

• complex mixture of products. At the same time the blocking of ESIPT-processes by the modification of the hydroxy group allows one to direct the photoreaction exclusively to the pathway of 6π-electrocyclization of the 1,3,5-hexatriene system. Thus, the study of the photochemical properties of similar

• we can assume that the key difference of the related pyrazole derivatives considered in this report is the absence of a pathway associated with 6π-electrocyclization. Therefore, we supposed that for the corresponding pyrazoles 12 containing a hydroxy group in the allomaltol fragment only ESIPT

• considered photoprocess. Probably, the DMF molecule forms an intermolecular hydrogen bond with the hydroxy group of the allomaltol fragment leading to complete suppression of the ESIPT process. Finally, AcOH was used as a solvent for the photochemical synthesis of α-hydroxy-1,2-diketone 14a. The starting

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• bromopropargylic alcohols under the reported conditions. The bromopropargylic alcohols are readily available from acetylenic alcohols and hypobromite [22] or N-bromosuccinimide [23]. The presence of the hydroxy group expands the synthetic potential of these bromoacetylenes. Thus, we have recently demonstrated a

Amamistatins isolated from Nocardia altamirensis

• Till Steinmetz,
• Wolf Hiller and
• Markus Nett

Beilstein J. Org. Chem. 2022, 18, 360–367, doi:10.3762/bjoc.18.40

• oxygen atom. A comparison of the NMR data with 3 revealed that the chemical shifts of CH2-24 are significantly shifted upfield. In contrast, all other resonances are highly conserved and no difference in the splitting pattern was observed. This suggests the presence of an electron-donating hydroxy group

Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase

• Peterson de Andrade,
• Sanaz Ahmadipour and
• Robert A. Field

Beilstein J. Org. Chem. 2022, 18, 208–216, doi:10.3762/bjoc.18.24

• hydrophobicity is important to inhibition of neuraminidase as the most potent compounds possess hydrophobic aromatic substituents. Conversely, increase in polarity results in weak inhibition (ca. 5%) as noted for compounds bearing substituents with nitrogen or a hydroxy group (3d–g). In fact, the higher polarity

Glycosylated coumarins, flavonoids, lignans and phenylpropanoids from Wikstroemia nutans and their biological activities

• Meifang Wu,
• Xiangdong Su,
• Yichuang Wu,
• Yuanjing Luo,
• Ying Guo and
• Yongbo Xue

Beilstein J. Org. Chem. 2022, 18, 200–207, doi:10.3762/bjoc.18.23

• absorption bands at 325 and 293 nm indicated the presence of a coumarin-type chromophore. The IR spectrum of 1 demonstrated absorption bands characteristic for an hydroxy group (3266 cm−1), α,β-unsaturated carbonyl group (1739 and 1701 cm−1), and an aromatic ring (1624 and 1457 cm−1). The 1H NMR spectrum of

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• only solvent-ionizing power. Shallow maxima observed when selectivity values (S, indicating the extent of product formation involving replacement of the chloride by the alkoxy group from an alcohol molecule reactive to replacement by the hydroxy group of a water molecule) could be due to two reaction

• or water molecule, leading to four possible reaction pathways, with two leading to replacement of the chloride by an alkoxy group and two to replacement by a hydroxy group. In a 2007 article [49] with “Dual Reaction Channels” in both the title and the “Key Words,” there is extensive dispersal between

Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

• Sandeep Kumar,
• Jyotirmoy Maity,
• Banty Kumar,
• Sumit Kumar and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2022, 18, 95–101, doi:10.3762/bjoc.18.10

• -methyltetrahydrofuran following a chemoenzymatic pathway. Whereas, the protection of the primary hydroxy over the lone secondary hydroxy group in the key azido sugar precursor was achieved using bulky tert-butyldiphenylsilyl chloride (TBDPS-Cl) in pyridine in 92% yield following a chemical synthetic pathway. The

• % overall yield starting from compound 11, respectively (Scheme 2). The use of lipase as biocatalyst was employed for the selective acetylation of the primary hydroxy group present in trihydroxy nucleosides 14a,b. This led to the screening of two different lipases, viz Candida antarctica lipase-B (CAL-B

• temperatures ranging from 25–45 °C in an incubator shaker at 200 rpm. Lipozyme® TL IM (10 wt % of the substrate) in 2-Me-THF at 40 °C was found to be the most suitable solvent for exclusive acetylation of the primary hydroxy group present in compounds 14a,b in quantitative yields (Scheme 3). Further, the

Photophysical, photostability, and ROS generation properties of new trifluoromethylated quinoline-phenol Schiff bases

• Inaiá O. Rocha,
• Yuri G. Kappenberg,
• Wilian C. Rosa,
• Clarissa P. Frizzo,
• Nilo Zanatta,
• Marcos A. P. Martins,
• Isadora Tisoco,
• Bernardo A. Iglesias and
• Helio G. Bonacorso

Beilstein J. Org. Chem. 2021, 17, 2799–2811, doi:10.3762/bjoc.17.191

• supported the structures of the Schiff bases 3. Additionally, the hydrogens of the hydroxy group were observed at 13.12 ppm, on average. The analysis of the 13C NMR spectra in CDCl3 for the new Schiff bases 3 showed chemical shifts in the 162.68–164.71 ppm range for the CH=N moiety, which agrees with

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• isoxazolidine-4,5-diols in the presence of anhydrous cerium chloride [17], which proceeded in a highly syn-diastereoselective manner due to the presence of the unprotected hydroxy group in the α-position. Accordingly, the diol 3 will be examined in the reaction with vinylmagnesium bromide with an emphasis on

• the expected high syn diol diastereoselectivity (Scheme 1). The obtained anti,syn-(hydroxyamino)alkenol 4 will be then subjected to reductive cleavage of the N–O bond. Next, a key intermediate epoxide 5 with the desired syn (threo) configuration between the hydroxy group and the epoxide oxygen could

• be prepared by substrate-directed epoxidation. A subsequent SN2 intramolecular epoxide ring-opening cyclization could provide an N-Cbz-protected pyrrolidine derivative with a hydroxymethyl group at C-5 and with trans configuration relative to the hydroxy group at C-4. Finally, (±)-codonopsinol B (1

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• incorporated into the growing DNA strand. However, the absence of a 3'-hydroxy group prevents further strand elongation. The anticancer and antiviral activity of 2’,3’-dideoxynucleosides is mainly based on inhibition of DNA synthesis, either through the chain termination process or by competitive inhibition [3

• with natural nucleotides for incorporation into the growing HIV DNA chain. The result if the triphosphate is taken up is the termination of the chain elongation because the drug lacks the 3’-hydroxy group on the deoxyribose ring that is necessary for the sugar–phosphate linking as shown in Figure 2

• % aqueous sulfuric acid, the isopropylidene group of 13 was selectively deprotected at 70 °C in dioxane to obtain diol 14. This diol was further cleaved using lead tetraacetate, and further reduction with sodium borohydride produced compound 15. The 5'-hydroxy group of 15 was then treated with tert

Solvent-free synthesis of enantioenriched β-silyl nitroalkanes under organocatalytic conditions

• Akhil K. Dubey and
• Raghunath Chowdhury

Beilstein J. Org. Chem. 2021, 17, 2642–2649, doi:10.3762/bjoc.17.177

• ]. In addition, the C–Si bond can be oxidized to a hydroxy group by Tamao–Fleming oxidation [3][4] or to an alkene unit via protodesilylation [5][6]. Many complex natural products, bioactive molecules, and drug molecules have been synthesized on exploitation of the above-mentioned properties of

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• –91%) with excellent levels of stereocontrol (≈92% ee, >20:1 dr in all cases). The ketone group in the cascade product was reduced asymmetrically to a chiral secondary hydroxy group (Table 1) [26]. In this case, the role of Ph3CCO2H as additive is to furnish the conjugate base Ph3CO2− anion which

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

• features the 1,2-shift of an alkyl or aryl group. In the process, the hydroxy group is converted to a carbonyl and the aldehyde/ketone or imine is converted to an alcohol or amine. Such α-ketol/α-iminol rearrangements are used in a wide variety of synthetic applications including asymmetric synthesis

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

• (−)-DIPT affording ent-85 in 65% yield. A series of functional group transformations involving hydroxy group protection, reduction of the epoxide, protection of the resultant free alcohol as TBS ether, and removal of the acetal protection afforded the expected allylic alcohol 83. Accordingly, cross

Synthesis and antimicrobial activity of 1H-1,2,3-triazole and carboxylate analogues of metronidazole

• Satya Kumar Avula,
• Syed Raza Shah,
• Khdija Al-Hosni,
• Muhammad U. Anwar,
• Rene Csuk,
• Biswanath Das and
• Ahmed Al-Harrasi

Beilstein J. Org. Chem. 2021, 17, 2377–2384, doi:10.3762/bjoc.17.154

• group. The first step was initiated by the protection of the primary hydroxy group of metronidazole (1) with p-toluenesulfonyl chloride in dry DCM in the presence of triethylamine at 0 °C to room temperature. The reaction afforded the desired metronidazole tosylate 2 in high yield (96%) [17]. In the

• 1H-1,2,3-triazole was based on its known activities and its broad range of applications in biochemical, pharmaceutical, biomedicinal and materials sciences [4][5]. Results and Discussion Chemistry: synthesis of 1H-1,2,3-triazole analogues of metronidazole Metronidazole (1) has a free primary hydroxy

Phenolic constituents from twigs of Aleurites fordii and their biological activities

• Kyoung Jin Park,
• Won Se Suh,
• Da Hye Yoon,
• Chung Sub Kim,
• Sun Yeou Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2021, 17, 2329–2339, doi:10.3762/bjoc.17.151

• ][11]. The data for compound 1 were similar to those of glochidioboside isolated from Glochidion obovatum [12], except for the presence of a hydroxy group instead of the methoxy group at C-3′ in 1. The two-dimensional structure of 1 was elucidated via analysis of COSY, HSQC, and HMBC spectroscopic data

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• well as branched β(1–3)-glucans with defined lengths could be prepared by AGA [140][141][142]. The poor nucleophilicity of the C-3 hydroxy group on the glycosyl acceptor required the use of more reactive glycosyl phosphate donors and, in some cases, a double glycosylation cycle [118][143]. Longer

• solubility of β(1–3)-glucans, compared to the β(1–4) analogues, has permitted the chemical or enzymatic synthesis of long polysaccharides. Still, the poor nucleophilicity of the hydroxy group at C-3, in the presence of a C-2 ester PG, could decrease the efficiency of chemical synthesis. Hence, there is scope

• for new strategies to provide anchimeric assistance, without affecting the nucleophilicity of the hydroxy group at C-3. β(1–6)-Glucans The formation of the β(1–6)-glycosidic bond poses less synthetic challenges than the β(1–3) bond. The primary C-6 hydroxy group is more nucleophilic than the secondary

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• , respectively, has proved to be the most effective for the promotion of the conjugate addition of 4-hydroxycoumarins 1 to 2-hydroxycinnamaldehydes 109, leading to chiral bridged bicyclic acetal products 110 with high ee (Scheme 35). The mechanistic study performed showed that possibly the phenolic hydroxy group

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• and the 3-keto group are crucial for its antibacterial activity whereas, acetylation of the C-6 hydroxy group reduces the activity of HA [169]. Previous studies have also shown the antitrypanosomal, antifungal and cilioinhibitory properties of HA [72][83][86][87][88]. For these properties and little

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• the phenol hydroxy group in the transition state. This assumption could also explain the high o-selectivity obtained in the fluorinations of naphthol, phenylurethane, and trimethylsilyl ether of phenol, and the exclusive 6-selectivity observed in the fluorination of conjugated enol triisopropylsilyl

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• C–N3 bond formation to afford 13 via the reaction with Mn(III)/L–N3. The anodic surface oxidizes the radical adjacent to the hydroxy group of the photocatalyst, thereby regenerating it. At the same time, the hydrogen atom abstraction of radical species of photocatalyst by Mn(III)–N3 could not be

Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate

• Eleni Dimitriou and
• Gavin J. Miller

Beilstein J. Org. Chem. 2021, 17, 1527–1532, doi:10.3762/bjoc.17.110

• separable amounts of 2 and 3 in 47% and 44% yields, respectively. Subsequent silyl protection of the C4-hydroxy group in 2 was completed using TBSOTf, furnishing 4 in 80% yield. Attempts to next convert 4 to 5 (via an N-cyanoethyl-protected tetrazole) using PPh3, DIAD and TMSN3 were unsuccessful, despite