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

• derivative 17. This was obtained as a mixture of endo- and exo-sulfoxides. Esterification of 17 was carried out with dimethyl sulfate to give methyl ester 18, which was further reduced using dichloroborane and dimethyl sulfide to provide sulfide 19 in 80% yield in THF as solvent. Hydrolysis of compound 19

• nuclear Overhauser effect (NOE) NMR spectroscopy are useful tools to monitor and control the chirality when utilizing a modified 1,3-oxathiolane intermediate 65 obtained via enzyme-catalyzed selective hydrolysis. Hu et al. [61] established a green catalyst, STS, for the asymmetric synthesis of lamivudine

• -catalyzed hydrolysis of protected racemic nucleosides to synthesize the enantiomerically pure oxathiolane nucleoside analogues 1 and 2 (Scheme 41). The protected racemic nucleoside derivatives 95 were synthesized by tin-mediated N-glycosylation of the corresponding acetate precursor 94 with silylated

AlBr₃-Promoted stereoselective anti-hydroarylation of the acetylene bond in 3-arylpropynenitriles by electron-rich arenes: synthesis of 3,3-diarylpropenenitriles

• Yelizaveta Gorbunova,
• Dmitry S. Ryabukhin and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2663–2667, doi:10.3762/bjoc.17.180

• nitriles 1. At the last step of the reaction, a proton substitutes AlBr3, and final hydrolysis of the reaction mixture gives rise to nitriles 2. It should be noted that this AlBr3-promoted hydroarylation of acetylene nitriles 1 (Scheme 1) is a novel transition-metal (Pd, Pt, Rh, etc.)-free stereoselective

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• hydrolysis [8]. It has also been found that degradation of chitosan/dextran cryogels resulted in an average increase in pore size, possibly due to thinning of the pore walls and reduction in crosslinks [32]. In general, mechanical property analysis of degraded cryogels is a topic largely overlooked by

Synthesis of new substituted 7,12-dihydro-6,12-methanodibenzo[c,f]azocine-5-carboxylic acids containing a tetracyclic tetrahydroisoquinoline core structure

• Agnieszka Grajewska,
• Maria Chrzanowska and
• Wiktoria Adamska

Beilstein J. Org. Chem. 2021, 17, 2511–2519, doi:10.3762/bjoc.17.168

• 5a, glyoxylic acid hydrate (4), and O-benzylvanilin-derived aminoacetal 3e (Scheme 4), when treated with 20% HCl or 70% HClO4 gave a colored complex mixture of decomposition products, probably due to the hydrolysis of the benzyl ether. Iwakuma et al. [15] reported the synthesis of 1,2,3,4

• difficult and resulted in a moderate yield of 12 (41%) due to insufficient differences in the Rf values of compound 12 and the by-product 2,3-dimethoxybenzyl alcohol (not shown), formed through the hydrolysis of 13 (Scheme 8). In this situation N-(2,3-dimethoxybenzyl)veratrylamine 10 was chosen as the

• proposed a plausible mechanism for the reaction of 6a with diluted HCl (Scheme 10). The mechanism consists of four major steps: the first step is an acid-catalyzed hydrolysis of the acetal function in 6a to afford aldehyde 15; the second step is the enolization of the aldehyde 15 to form the tautomeric

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

• rapid epimerization during cinnamate hydrolysis. Later, in 2013 Pereda-Miranda and co-workers isolated ten compounds, namely brevipolides A–J (1–10), from the aerial part of Hyptis brevipes Poit. collected in Mexico [12]. The C6’S configuration was then determined by X-ray crystallographic data of the

Isolation and characterization of new phenolic siderophores with antimicrobial properties from Pseudomonas sp. UIAU-6B

• Emmanuel T. Oluwabusola,
• Olusoji O. Adebisi,
• Fernando Reyes,
• Kojo S. Acquah,
• Mercedes De La Cruz,
• Larry L. Mweetwa,
• Joy E. Rajakulendran,
• Digby F. Warner,
• Deng Hai,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2021, 17, 2390–2398, doi:10.3762/bjoc.17.156

• shown in Figure S47 (Supporting Information File 1). Retention times (min) for the derivatized (ʟ-FDAA) threonine standards and for the observed peaks in the HPLC trace of each ʟ-FDAA-derivatized hydrolysis product under the reported conditions were as follows: retention times of standards: ʟ-Thr: 19.62

Allylic alcohols and amines by carbenoid eliminative cross-coupling using epoxides or aziridines

• Matthew J. Fleming and
• David M. Hodgson

Beilstein J. Org. Chem. 2021, 17, 2385–2389, doi:10.3762/bjoc.17.155

• %), which arises from hydrolysis during work-up of the enamine that is formed from trapping of the lithiated epoxide by LTMP [9][10]. Omitting LTMP gave a significantly improved yield of the allylic alcohol 6 (79%, using BuLi and stannane 4 (3 equiv each)). This latter result suggests that

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

• (Figure 2). The locations of the glucose unit and the methoxy group were confirmed from the observed HMBC correlations of H-1′′/C-9′ and 3-OCH3/C-3, respectively (Figure 2). Acid hydrolysis of 1 was conducted to analyze the aglycone and sugar moiety. The structure of the aglycone (1a) was confirmed as

• characteristic J value of the anomeric proton (1.5 Hz) confirmed the rhamnose as α-form (Figure 2) [10]. Acid hydrolysis of compound 2 afforded the aglycone, dihydrodehydrodiconiferyl alcohol (2a) [18], and ʟ-rhamnose ([α]D25 +9.0), which was identified in an identical manner to that of compound 1. The

• obtained by acid hydrolysis of 3 was confirmed based on 1H NMR and MS data [20]. The absolute configuration of 3a was established as 8S (a negative CE at 273 nm) based on the comparison of its ECD spectrum with the reported data [21]. Thus, the structure of compound 3 was determined as 8S

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• The concept of anion-binding catalysis was first penned by Schreiner et al. in 2006, who realized the acetalization of benzaldehyde (1) with a thiourea catalyst (3, Scheme 1) [30][31]. They proposed the reaction to proceed via thiourea-catalyzed orthoester hydrolysis, leading to the formation of a

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

• Luiz Claudio Ferreira Pimentel,
• Lucas Villas Boas Hoelz,
• Henayle Fernandes Canzian,
• Frederico Silva Castelo Branco,
• Andressa Paula de Oliveira,
• Vinicius Rangel Campos,
• Floriano Paes Silva Júnior,
• Rafael Ferreira Dantas,
• Jackson Antônio Lamounier Camargos Resende,
• Anna Claudia Cunha,
• Nubia Boechat and
• Mônica Macedo Bastos

Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144

• the 1,2,3-triazole core strategically in the design of new compounds [18][19]. The explanation for this interest is associated with its resistance towards oxidation, reduction, and acidic or basic hydrolysis reactions that occur in phase I of human metabolism [20][21]. The application of this core

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

• , the developed GA-polyHMPA initially exhibits UCST responsiveness, but can subsequently be slowly biodegraded to a fully water-soluble polymer (polyHMPA) via hydrolysis. Initial in vivo studies of a sustained release of either a hydrophilic model protein or a hydrophobic dye entrapped within the

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

• Buchwald amination led to the 4-amino-substituted compounds 158 or acids 159 after basic hydrolysis (Scheme 21) [108]. Compound 159c had the maximum potency against IDO1 and TDO with IC50 values of 2.72 mM and 3.48 mM, respectively compared to 159a and 159b, which is 15 and 28.5 times higher than that of

• -mediated coupling of N-silylated 6-hydroxyindole 174 with the corresponding boronic acid 173 (Scheme 24) [114]. For further synthetic transformations of 175, N-protection with bromo esters 176 followed by hydrolysis towards acids 177a and 177b were performed. The products 177a and 177b are potent anti-HIV

An initiator- and catalyst-free hydrogel coating process for 3D printed medical-grade poly(ε-caprolactone)

• Jochen Löblein,
• Thomas Lorson,
• Miriam Komma,
• Tobias Kielholz,
• Maike Windbergs,
• Paul D. Dalton and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2021, 17, 2095–2101, doi:10.3762/bjoc.17.136

• improved by a variety of methods like plasma treatment, NaOH hydrolysis treatment or a micro deposition system. This study outlines a potential approach to coat medical-grade PCL with a thin hydrogel that requires no initiator or catalyst – just a deoxygenated aqueous monomer solution and UV light. We

Preparation of mono-substituted malonic acid half oxyesters (SMAHOs)

• Tania Xavier,
• Sylvie Condon,
• Christophe Pichon,
• Erwan Le Gall and
• Marc Presset

Beilstein J. Org. Chem. 2021, 17, 2085–2094, doi:10.3762/bjoc.17.135

• MAHOs [24][25][26][27]; and a Michael addition for 3'-oxoalkyl-substituted MAHOs [28]. As studied by Niwayama [29], the hydrolysis step is generally achieved by saponification using alcoholic KOH (or NaOH) [30][31][32][33][34][35][36], but other selective cleavages of one ester group are possible [37

• led to lower but still useful yields (3ak, 41%; 3bl, 44%; 3bm, 51%). In all these cases, the hydrolysis step delivered the expected SMAHOs in good to excellent yields. However, this reaction should be performed in a water/alcohol mixture, this latter being the same as the ester substituent to avoid

• efficiency, this second strategy required an additional step of hydrolysis of a substituted malonate to prepare the requisite substituted malonic acid. Monoesterification route In order to take advantage of the preparation of substituted malonates 3, we decided to explore a more straightforward strategy, the

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

• only small modifications, hampering the formation of unnatural polymers. Low glycosylation yields and product hydrolysis represent additional hurdles associated with enzymatic synthesis of polysaccharides [23]. With this approach, homopolymers are often obtained as non-uniform samples, because the

• yields (2–5%). This approach circumvented the precipitation of the water-insoluble oligomers and allowed for chain elongation [72][73]. This methodology was improved employing a protic co-catalyst system to yield DP > 120 in a 26% conversion [74]. Generally, an acid catalyst would promote the hydrolysis

• differences in the conformational behavior of the two analogues (β(1–3) vs β(1–4) oligomers), it was observed that the β(1–3)-mimetic was still recognized by wheat germ agglutinin and a chitinase enzyme, and could act as a moderate inhibitor of chitin hydrolysis [268]. Mannose- and rhamnose-based

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• -methoxybenzaldehyde imine derivatives with phenyl Grignard reagents as coupling partners. As the catalyst CrCl2 is used and either 2,3-dichlorobutane (DCB) or 1,2-dichloropropane (DCP) are used as oxidant to give 2,5-diarylbenzaldehyde after imine hydrolysis (Scheme 16B). Although benzaldehyde is a basic structure

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• stability was observed relative to their unmodified ON [113][114]. Interestingly, a difference in hydrolysis rate was noticed: the aminomethyl (69) modification was readily hydrolysed at pH 7 whereas the aminoethyl (70) modification was completely stable under the same conditions [114]. A preliminary cell

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• the faster hydrolysis of the in situ generated imine intermediates, aromatic aldehydes containing electron-withdrawing substituents afforded no product in the reaction. It was proved that a variety of aliphatic primary amines can efficiently produce the triazole products (Scheme 14) [45]. This one-pot

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• hydroalkylation reactions of less activated substrates [31]. Later studies demonstrated that the true reason for the reaction success was not the putative in situ formation of silyl enol ethers but the HCl formation due to TMSCl hydrolysis. The HCl catalyzed the formation of the enolic form responsible for the

• nucleophilic attack on the metal-complexed olefin (see Scheme 3, intermediate A). Taking advantage of HCl as an additive (or generated in situ by silyl chloride hydrolysis), Widenhoefer described the intramolecular hydroalkylation of even less reactive alkenyl ketones 4 under Pd(II) catalysis, with minor

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• pathway involves electrophilic addition para to the phenol to form the ipso-substituted nitro 12 compound. Subsequent rearrangement of the nitro species 12 to the nitrito dienone 13, by homolysis and recombination of the radical pair, is followed by hydrolysis to furnish alcohol 6 [70]. Addition of the

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• hydrolysis using 18% aq HCl furnishing the corresponding aldehyde [21]. Without purification, the resultant aldehyde intermediate was then directly reduced using potassium borohydride to the corresponding primary alcohol 11a in 74% yield starting from 9a. Pd-catalyzed cross-coupling of 11a with pinacol

Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• , followed by hydrolysis with solid K2CO3 and water for 30 min (Scheme 5). The desired aldehyde 18 was recovered in an excellent yield of 99%, and product epimerization was not detected based on 13C NMR spectroscopic analysis. This was confirmed by analysis of the 13C chemical shifts of the acetonide group

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• reaction of 3,5-di-tert-butyl-1,2-benzoquinone with 5′-amino-5′-deoxy-2′,3′-O-isopropylideneuridine (67) and 5′-amino-2′,5′-dideoxyadenosine (70). The unprotected double-headed nucleoside (R)-N1-(4-(4,6-di-tert-butylbenzoxazol-2-yl)-β-ᴅ-erythrofuranosyl)uracil (69) was obtained by acidic hydrolysis of the

• nucleoside 5′-(R)-C-(thymin-1-ylmethyl)-3′-O-(tert-butyldimethylsilyl)thymidine (108) was synthesized by treating the double-headed nucleoside 107 with triflic anhydride followed by basic hydrolysis (Scheme 24) [31]. Subsequently, the double-headed nucleoside 107 was incorporated into oligonucleotides [31

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• amine, affording a 6-aminopyridone, which, after acidic treatment, is turned into the same β,β-disubstituted glutarate formed by hydrolysis of the pyridone from the type-IV Guareschi reaction. This modification of the type-IV Guareschi reaction is the “real” Guareschi–Thorpe reaction, which in many

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

• as a chiral auxiliary which was then removed by hydrolysis in the final step of the overall seven-step synthesis. Deprotonation of 41 using LiHMDS in THF in a primary reactor was performed at −40 °C and telescoped into a second reactor along with a stream containing the trityl-protected aldehyde, 42