Chiral isothiourea-catalyzed kinetic resolution of 4-hydroxy[2.2]paracyclophane

• David Weinzierl and
• Mario Waser

Beilstein J. Org. Chem. 2021, 17, 800–804, doi:10.3762/bjoc.17.68

• transformation into diastereomers by esterification with chiral acid chlorides [19][20] as well as the kinetic resolution (KR) of racemic esters of 2 via an enzymatic hydrolysis [25][26][27] were very successfully used to access enantioenriched 2. Recently, Akiyama and co-workers reported the kinetic resolution

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• ; moreover, 53 and 54 can be mutually transformed. Excited state 53 reacts with diene 49, forming a double radical intermediate 55 that subsequently evolves to cyclobutyliminium ion 56, and then product 50 is provided after hydrolysis, along with the release of diamine 51. In 2020, Zhang and colleagues [25

Synthesis of dibenzosuberenone-based novel polycyclic π-conjugated dihydropyridazines, pyridazines and pyrroles

• Ramazan Koçak and
• Arif Daştan

Beilstein J. Org. Chem. 2021, 17, 719–729, doi:10.3762/bjoc.17.61

• pyrrole and acetate structures. The acetate is formed by reducing the carbonyl group to alcohol and then reacting this alcohol with acetic acid. After hydrolysis of the acetate group with sodium hydroxide, alcohol derivate 10bb was formed. Oxidation of alcohol 10bb with MnO2 led to the formation of the

β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes

• Zafar Iqbal,
• Lijuan Zhai,
• Yuanyu Gao,
• Dong Tang,
• Xueqin Ma,
• Jinbo Ji,
• Jian Sun,
• Jingwen Ji,
• Yuanbai Liu,
• Rui Jiang,
• Yangxiu Mu,
• Lili He,
• Haikang Yang and
• Zhixiang Yang

Beilstein J. Org. Chem. 2021, 17, 711–718, doi:10.3762/bjoc.17.60

• compounds 11 and 12, respectively, in two steps. In the first step, the ester derivatives were N-acylated by acetic anhydride in CH2Cl2 followed by hydrolysis using aqueous NaOH in THF to afford the required intermediates 3 and 4 in overall good yields. Compound 5 was obtained by direct acylation of the

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

• prepared by epoxidation of the cyclooctenediol with m-chloroperbenzoic acid followed by hydrolysis with HBr(g) in methanol. Treatment of bromotriol with NaN3 and the reduction of the azide group yielded the other desired 3-aminocyclooctanetriol. Hydrolysis of the epoxides with HCl(g) in methanol gave

• cyclic sulfate 9 in 95% yield. The cyclic sulfate moiety in 9 was reacted with sodium azide in DMF at 80 °C followed by acidic hydrolysis of the resulting acyclic sulfate ester to give azidotriol 10 as a single stereoisomer in 97% yield (Scheme 2). For further structural proof, the azidotriol 10 was

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• with a covalently attached fullerene molecule [86]. To this end, adduct 13 was obtained from 4-(tert-butoxycarbonyl)phenyldiazomethane and fullerene. Subsequent acid hydrolysis of the protective ester group quantitatively gave a derivative of carboxylic acid 14, a versatile synthon for the synthesis of

• formed. In fact, a series of spirocyclopentalydenemethanofullerenes 190–193 were obtained by the reaction of C60 with lithium salts of tosylhydrazone (Scheme 34) [154]. Spiromethanofullerene 194 was prepared on the basis of monoethylene glycol tosylhydrazone. Hydrolysis of the former resulted in 6,6

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• (a solvent is the reagent and solvolyses include hydrolysis, glycolysis, alcoholysis and aminolysis) and hydrogenolysis reactions (H2 as reagent). Hydrolysis (sometimes called hydrocracking) is in between thermochemical and chemolytic processing, basically consisting of depolymerisation by the

• developed, using a solvent or molecular hydrogen as cleaving agents [81]. The main solvolytic process include: hydrolysis (water) alcoholysis (methanol, ethanol, 1-butanol, 2-ethyl-1-hexanol, phenol) glycolysis (ethylene glycol (EG), 1,2-propanediol (PD), 1,3- and 1,4-butanediol (BD)), diethylene glycol

• (DEG), dipropylene glycol (DPG)) aminolysis (2-aminoethanol, 3-amino-1-propanol, ethylenediamine). Advantages of catalytic processes are obvious and can be witnessed in the hydrolysis and the glycolysis reactions of poly(ethylene terephthalate) (PET) [82][83]. Representative data are reported in

Breakdown of 3-(allylsulfonio)propanoates in bacteria from the Roseobacter group yields garlic oil constituents

• Anuj Kumar Chhalodia and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 569–580, doi:10.3762/bjoc.17.51

• from 9, followed by a series of proposed spontaneous reactions [5][8]. Through these transformations, acid 10 can undergo a dimerization with elimination of water to allicin (5). The hydrolysis of 5 results in allylsulfinic acid (12) and allyl thiol (13), the latter of which can react with another

• giving another example for the complex interactions between marine bacteria and algae. Known DMSP degradation pathways include its hydrolysis to dimethyl sulfide (DMS) and 3-hydroxypropanoic acid (15) by the enzyme DddD [19], or the lysis to DMS and acrylic acid (16) for which various enzymes including

• collapses to methanethiol (MeSH) and malonyl-CoA semialdehyde (21). This compound further degrades to acetaldehyde (22) through the thioester hydrolysis and decarboxylation [27]. Feeding of (methyl-2H6)DMSP to Phaeobacter inhibens DSM 17395 and Ruegeria pomeroyi DSM 15171 resulted in the efficient uptake of

Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs

• Kenji Morokuma,
• Shuntaro Tsukamoto,
• Kyosuke Mori,
• Kei Miyako,
• Ryuichi Sakai,
• Raku Irie and
• Masato Oikawa

Beilstein J. Org. Chem. 2021, 17, 540–550, doi:10.3762/bjoc.17.48

• ], the heterotricyclic framework was constructed over a five-step sequence including the domino metathesis reaction as a key step to give (rac)-7. The subsequent three steps from (rac)-7 (esterification with CH2N2, PMB removal, and ester hydrolysis) had been proven to be promising for the preparation of

• in small molecules and biomacromolecule due to intermolecular or intramolecular H-bonds and/or hydrophobic interactions [13]. Hydrolytic deprotections were finally examined to complete the synthesis. The previously employed alkaline hydrolysis (1 M aq LiOH, MeOH or THF, rt→45 °C) [4], however, gave

• hand, (2S)-MC-27 (4*) was synthesized in a reasonable yield (62%) by acidic hydrolysis (Scheme 4). The chromatographic behavior and the spectroscopic data (1H and 13C NMR) of (2S)-MC-27 (4*) thus synthesized were identical to those of the antipode 4 (see above as well as Scheme 3 and Scheme 4

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• and selective hydrolysis. Synthesis of α-phosphonodepsipeptides In 1987, a series of phosphonodepsidipeptides 10 was synthesized as phosphorus analogues of peptides and evaluated as inhibitors of leucine aminopeptidase from porcine kidney and two compounds, i.e., 10e and 10h (R = isobutyl, benzyl

• ) were modest inhibitors. The synthesis started from diphenyl N-Cbz-1-aminoalkylphosphonates 11 (Scheme 1). They were transformed to dimethyl esters via transesterification and further to monomethyl esters 12 via basic hydrolysis. After chlorination with thionyl chloride, the monomethyl esters 12 were

• methyl N-Cbz-protected 1-aminoethylphosphonochloridate 13b with methyl ᴅ-lactate (22a) and methyl mercaptoacetate (22b), respectively, followed by a basic hydrolysis and hydrogenolysis. The bioassay results indicated that the phosphonothiodepsidipeptide 20b did not inhibit VanX (Scheme 3) [21]. It was

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• (Figure 10B). If the mRNA codon matches the anticodon of the tRNAPro, GTP undergoes hydrolysis, allowing the elongation factor Tu to leave the complex. This event is followed by the peptidyl transfer reaction, which forms a new peptide bond. Subsequently, the ribosome binds the elongation factor G

• carrying a molecule of GTP, the hydrolysis of which leads to a translocation event in which the empty tRNA leaves and peptidyl-tRNA moves to the P-site. The A-site remains empty, allowing the next ternary complexes to bind in response to the next codon in the mRNA sequence [84]. The translational

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• examined [46]. Trifluoromethyl ketones (TFMKs) are valuable fluorine-containing synthetic targets of bioactive compounds [55][56] that behave as mimics of the tetrahedral transition-state intermediate of enzymatic hydrolysis of esters and amides by stabilizing their hydrates (Figure 1a) [57]. In fact, the

• . Trifluoromethyl ketones. a) Hydrolysis of trifluoromethyl ketones. b) Selected examples of biologically active trifluoromethyl ketones. Chemistry of the CF3 anion generated from HCF3. a) Decomposition of the trifluoromethyl anion to difluorocarbene and fluoride. b) A hemiaminaloate adduct of CF3 anion to DMF. c

Identification of volatiles from six marine Celeribacter strains

• Anuj Kumar Chhalodia,
• Jan Rinkel,
• Dorota Konvalinkova,
• Jörn Petersen and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 420–430, doi:10.3762/bjoc.17.38

• mass spectra of A) unlabeled 2-(methyldisulfanyl)benzothiazole (41) and of labeled 41 after feeding of B) (methyl-2H3)methionine, C) (methyl-13C)methionine and D) (34S)DMSP. Sulfur metabolism in bacteria from the roseobacter group. A) DMSP demethylation by DmdABCD, B) DMSP hydrolysis by DddP and lysis

1,2,3-Triazoles as leaving groups: S_NAr reactions of 2,6-bistriazolylpurines with O- and C-nucleophiles

• Dace Cīrule,
• Irina Novosjolova,
• Ērika Bizdēna and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 410–419, doi:10.3762/bjoc.17.37

• 4a. Also hydrolysis of 2c into 4b proceeded under mild conditions and only gentle warming to 50 °C was required. 2,6-Bistriazolylpurine derivatives in SNAr reactions with C-nucleophiles Next, SNAr reactions between 2,6-bistriazolylpurine 2c and C-nucleophiles offered an easy way for the C–N bond

• yield of compound 5d was obtained due to the ethyl ester hydrolysis and subsequent decarboxylation. Such side reactions were also observed for similar compounds in literature [79][80]. As a limitation of the method we have found that 2,6-bistriazolylpurine 2c was inert to SNAr reactions with

Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives

• Alexander Leslie,
• Thomas S. Moody,
• Megan Smyth,
• Scott Wharry and
• Marcus Baumann

Beilstein J. Org. Chem. 2021, 17, 379–384, doi:10.3762/bjoc.17.33

• furthermore allowed the ester/nitrile moieties to be unaffected. Indeed, it was established subsequently that alkaline hydrolysis of the ester group requires a prolonged reaction time at an elevated temperature (Scheme 6). Importantly this can be achieved selectively without a concomitant cleavage of the

• . Batch hydrolysis of the ester group in the presence of the carbamate. Supporting Information Supporting Information File 4: Experimental details and spectroscopic data. Funding We gratefully acknowledge support from Science Foundation Ireland through the SFI Industry Fellowship Program for the project

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

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

• operations overall from methyl N-Boc-prolinate. The key step proceeds in each case via N,O-diacylation, then selective oxidative hydrolysis of the intermediate bicyclic pyrrole and establishes a precedent for the synthesis of related C(7a)-hydroxylated pyrrolizidines. Keywords: acyloxypyrroles; bacterial

• Baeyer–Villiger-type ring expansion, hydrolysis and decarboxylation, cyclization and dehydration, and finally hydroxylation at C(7a). Just one month later, Bode reported the identification of an unknown gene cluster in the symbiotic bacterium Xenorhabdus stockiae [23]. Cloning and expression of this

• spectrum) and a shift in the C(7a) resonance. The complication of solvent incorporation was avoided by running both the acylation and oxidative hydrolysis steps in acetonitrile, with water added in the second step. The oxidation step could be carried out either with a stoichiometric amount of I2, or just

Regioselective chemoenzymatic syntheses of ferulate conjugates as chromogenic substrates for feruloyl esterases

• Olga Gherbovet,
• Fernando Ferreira,
• Apolline Clément,
• Mélanie Ragon,
• Julien Durand,
• Sophie Bozonnet,
• Michael J. O'Donohue and
• Régis Fauré

Beilstein J. Org. Chem. 2021, 17, 325–333, doi:10.3762/bjoc.17.30

• , France 10.3762/bjoc.17.30 Abstract Generally, carbohydrate-active enzymes are studied using chromogenic substrates that provide quick and easy color-based detection of enzyme-mediated hydrolysis. For feruloyl esterases, commercially available chromogenic ferulate derivatives are both costly and limited

• ; hydrolysis; lipase; transesterification; Introduction The development of “white biotechnology” is underpinned by advances in enzyme discovery and engineering, areas that are being driven by metagenomics and in vitro-directed enzyme evolution. These techniques procure massive discovery or the creation of new

• preparation of bioactive compounds with potential antioxidant properties [2][3][4][5]. Operating via a two-step serine protease mechanism involving a conserved Ser-His-Asp/Glu catalytic triad [6][7], Faes catalyze the hydrolysis of ester bonds linking hydroxycinnamoyl groups to the glycosyl moieties of plant

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• inhibitors in situ using 19F NMR spectroscopy (Figure 6). For this, the activity of the membrane-bound FAAH enzyme was evaluated by monitoring the hydrolysis of a fluorinated anandamide analogue ARN1203, a previously reported FAAH substrate, to arachidonic acid and 1-amino-3-fluoropropanol in the presence

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

• organic phase, making hydrolysis the dominant reaction pathway. However, the reaction of chlorodifluoromethane with concentrated KOH in dioxane in the presence of tetraphenylarsonium chloride as the catalyst, provided low yields (<30%) of the cyclopropanation products [9]. Therefore, another modified

• was found to be superior to both CsF and KF as an initiator. Difluorocarbene generated from TFDA (25) also readily reacted with propargyl esters 27 at the triple bond (Scheme 13). The difluorocyclopropenes 28 were further converted into the difluorocyclopropyl ketones 29 by alkaline hydrolysis and

• hydrogenolysis of benzyl ethers (H2, Pd) [72], DIBAL-H reduction of esters to form alcohols [73], oxidative cleavage of vinyl groups to form carboxylic acids (KMnO4) [74], and the conversion of the acids into amines using the Curtius rearrangement (SOCl2, followed by Me3SiN3, thermolysis, and acid hydrolysis of

Selective synthesis of α-organylthio esters and α-organylthio ketones from β-keto esters and sodium S-organyl sulfurothioates under basic conditions

• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Thiago Barcellos,
• Claudio C. Silveira and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2021, 17, 234–244, doi:10.3762/bjoc.17.24

• role in the selective formation of 3, but the exact operation of O2 during this process remains unclear at this stage. A tentative pathway for the formation of compound 4 is proposed in Scheme 5. It is well documented that with a dilute amount of base, ester hydrolysis followed by saponification takes

• place in β-keto esters, which is followed by CO2 displacement under heating [61][62][63][64]. We assume that in our case, when only 2 equiv of base are used, the keto–enol tautomer intermediates undergo a hydrolysis–decarboxylation process preferentially to a retro-Claisen reaction. This process forms

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• desired triazole derivatives were not obtained. Furthermore, the hydrolysis of the dialkyl ester groups were performed with TMSI [29][30], and phosphonic acid 10 was obtained. The latter was inert to the SNAr reaction with NaN3 at C2 (Scheme 4). SNAr–Arbuzov reaction between 2,6-bistriazolylpurines and P

Multiswitchable photoacid–hydroxyflavylium–polyelectrolyte nano-assemblies

• Alexander Zika and
• Franziska Gröhn

Beilstein J. Org. Chem. 2021, 17, 166–185, doi:10.3762/bjoc.17.17

• spectrum shows a small transformation to form B. The relatively weak intensity suggests that this was not due to the irradiation but the well-known hydrolysis. In case of form B, the 13C NMR data show that the irradiation leads to form Cc, which can be seen from the new peaks at 127 ppm, 134 ppm, and 175

• nm (state A) to RH = 163 nm (state C). The size of RH = 163 nm for state C of cycle II is the same size as at the end of cycle I. This leads to the conclusion that cycle I is reversible. This further is supported with the same sphere-like structure. The next step in cycle II is the hydrolysis of the

Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature

• Romain Pierre,
• Anne Brethon,
• Sylvain A. Jacques,
• Aurélie Blond,
• Sandrine Chambon,
• Sandrine Talano,
• Catherine Raffin,
• Branislav Musicki,
• Claire Bouix-Peter,
• Loic Tomas,
• Gilles Ouvry,
• Rémy Morgentin,
• Laurent F. Hennequin and
• Craig S. Harris

Beilstein J. Org. Chem. 2021, 17, 156–165, doi:10.3762/bjoc.17.16

• library building block acid chloride 2. The libraries were prepared in a 3-step manner: 1) amide coupling; 2) deprotection of the 2-methoxypyridine through hydrolysis at elevated temperatures; and 3) the final SNAr or Ullman step to introduce the amine vector with variable yields and chromatographic

• ). No product was observed via direct SNAr using KOH (Table 1, entry 1) [3]. Acidic conditions (Table 1, entries 2–5) [4], where we can expect protonation thus activation of the pyridine ring towards nucleophilic attack, resulted in only traces of product along with hydrolysis of the amide moiety at C-3

• pyridine ring toward SNAr with the −OAt anion in an intermolecular or intramolecular fashion (Scheme 3). We saw this observation as having the potential to solve our hydrolysis issues and decided to explore it further. Inspection of the literature revealed that activated ethers (e.g., OBt) have been

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

• Michał M. Więcław and
• Bartłomiej Furman

Beilstein J. Org. Chem. 2021, 17, 115–123, doi:10.3762/bjoc.17.12

• proton donor in the reaction mixture. Intriguingly, this behavior is inconsistent with the generally accepted mechanism of this transformation, which assumes the hydrolysis of TMSN3 to HN3 and activation of the imine species by protonation. Scheme 7 presents our proposal for the possible course of the

• undergoes a subsequent addition of an isocyanide moiety (intermediate V), followed by an azide anion addition. Intermediate VI undergoes a cyclization, producing VII, a silylated derivative of the expected product. The hydrolysis of VII most likely occurs during the reaction’s work-up. Preliminary DTF