Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• involve acetylation/deacetylation of histone proteins by histone deacetylases (HDACs) [1]. HDACs belong to an important family of enzymes consisting of 18 isozymes. They control protein acetylation, which is a change that occurs after translation. In addition, they regulate gene transcription, cell

• differentiation, cell cycle progression and apoptosis by targeting both histone and non-histone proteins. The balance between acetylation and deacetylation is pivotal for typical cell function. Abnormal or increased HDAC expression has been reported in several human tumors and cancer cell lines [2]. As such, the

Targeted photoswitchable imaging of intracellular glutathione by a photochromic glycosheet sensor

• Xianzhi Chai,
• Hai-Hao Han,
• Yi Zang,
• Jia Li,
• Xiao-Peng He,
• Junji Zhang and
• He Tian

Beilstein J. Org. Chem. 2019, 15, 2380–2389, doi:10.3762/bjoc.15.230

• 4 according to reported methods [27]. Then, the photochromic fluorophore intermediate 7 was synthesized by coupling compounds 3 and 6 through amidation. The Glyco-DTE reporter was prepared by click reaction between compound 7 and acetylated β-ᴅ-galactoside, followed by deacetylation. Similarly, a

Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides

• Rosana Ribić,
• Ranko Stojković,
• Lidija Milković,
• Mariastefania Antica,
• Marko Cigler and
• Srđanka Tomić

Beilstein J. Org. Chem. 2019, 15, 1805–1814, doi:10.3762/bjoc.15.174

• performed. Boc deprotection of obtained compound 6 gave the trifluoroacetic salt of peptide 7 which was used in the synthesis of mannoconjugates. The mannose precursor containing the glycolyl linker 11 was prepared in a three-step procedure shown in Scheme 3. The stereoselective α-anomeric deacetylation of

• peptide moieties. The tert-butyl deprotection was accomplished using a selective reagent, trifluoroacetic acid (TFA). Side products derived from deacetylation of compound 10 have not been detected. The synthesis of benzyl-protected α-mannoside containing a (R)-hydroxyisobutyryl linker was previously

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

• the hydroxy group preceded the aziridine ring opening with acetic acid while hydrogenation in the presence of Boc2O led to the formation of (3R,4R)-151. To conclude the synthesis of (2S,3R)-148 the hydroxymethyl group was recovered after basic deacetylation and it was further oxidized and esterified

Mechanochemical amorphization of chitin: impact of apparatus material on performance and contamination

• Thomas Di Nardo and
• Audrey Moores

Beilstein J. Org. Chem. 2019, 15, 1217–1225, doi:10.3762/bjoc.15.119

• is reduced by mechanical forces [17][24][50][51] or otherwise [52] by deforming particles and breaking lattice imperfections [50]. For biomass processing, amorphization has been used in several studies [24][53][54], either as a pretreatment [21] prior to deacetylation [18][55], enzymatic [22][56][57

Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection

• Chelsea L. Rintelmann,
• Tara Grinnage-Pulley,
• Kathleen Ross,
• Daniel E. K. Kabotso,
• Angela Toepp,
• Anne Cowell,
• Christine Petersen,
• Balaji Narasimhan and
• Nicola Pohl

Beilstein J. Org. Chem. 2019, 15, 623–632, doi:10.3762/bjoc.15.58

• of the CbzF-protected aminopentanol 7 afforded the monosaccharide 8 (Scheme 2). The 2-O-position was then deacylated, followed by iterative glycosylation/deacetylation with donor 3 to provide dimannoside acceptor 11. TCA-mannose donor 3 was initially used to cap the dimannoside 11. However

Cyclopropene derivatives of aminosugars for metabolic glycoengineering

• Jessica Hassenrück and
• Valentin Wittmann

Beilstein J. Org. Chem. 2019, 15, 584–601, doi:10.3762/bjoc.15.54

• Scheme 3. Alcohol 4 was activated with 4-nitrophenyl chloroformate, and the obtained carbonate 5 reacted with neutralized mannosamine and peracetylated as described above to give Ac4ManNCyoc(H2) in a yield of 57%. Deacetylation with N,N-ethyldimethylamine in methanol and further aldolase reaction and DMB

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• remained in the acetone washings. This patent also divulges the synthesis of 2,3,5-tri-O-acetyl-D-ribofuranosyl chloride (β/α ratio is 6:4) using an extruder with the aim of developing a continuous production of compound 4a. Deacetylation of 4a to give the desired β-NR+Cl− salt was studied under acidic (aq

• as recommended by Lee et al. [27]), and with subsequent – after the completion of deacetylation – evaporating excessive ammonia at temperatures also below 0 °C [25][39]. Moreover, because of the limitations associated with different stability to different pH ranges, the reduction of NR+ to NRH must

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

• removal of the chiral auxiliary with simultaneous formation of a N-Boc derivative 30. The hydroxymethyl to carboxylate transformation to form the protected diester (2S,3R)-31 required prior basic deacetylation followed by standard oxidation and esterification. Diastereoisomer (2S,3S)-31 was also prepared

Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence

• Gergő Mótyán,
• László Mérai,
• Márton Attila Kiss,
• Zsuzsanna Schelz,
• Izabella Sinka,
• István Zupkó and
• Éva Frank

Beilstein J. Org. Chem. 2018, 14, 2589–2596, doi:10.3762/bjoc.14.236

• heterocyclization. In order to enlarge the compound library available for pharmacological studies, the 3β-OH analogs 7a–j of the primary products 6a–j were also synthesized through simple alkaline deacetylation (Scheme 2, Table 1). The structures of all synthesized compounds were characterized by 1H and 13C NMR

D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• derivative of 10 was prepared. The acetyl groups of 10i can easily be removed by Zemplén deacetylation (Scheme 3) [34]. Instead of the classical protocol with sodium methoxide, ammonia in methanol was applied, because oxazolines are sensitive to acid and with ammonia no acid has to be added to neutralize the

• phosphines can be used as nucleophiles for deacetylation reactions [50][51]. We suppose that the lower yields of 5f–i and 14a can be explained by partial or full deacylation of the protective groups. This explanation is also in good accordance with the fact that the yield of the ester protected PHOX ligand

• different substitution pattern at positions 3, 4 and 5. PG: protective group, X: leaving group. Activation of 7 to oxocarbenium ion 9 in the Ritter reaction. Zemplén deacetylation of 10i. Benzylation of 10j to give 10b. Plausible mechanism of the Ritter reaction. For better clarity C-2 is not shown in

Phosphoramidite building blocks with protected nitroxides for the synthesis of spin-labeled DNA and RNA

• Timo Weinrich,
• Eva A. Jaumann,
• Ute M. Scheffer,
• Thomas F. Prisner and
• Michael W. Göbel

Beilstein J. Org. Chem. 2018, 14, 1563–1569, doi:10.3762/bjoc.14.133

• . Results and Discussion To prepare compound 5, the deoxyuridine derivative 9 [44] was activated by sulfonylation and then treated with the protected TEMPO building block 10 [43] to provide 11 (Scheme 1). After deacetylation, phosphitylation of 12 straightforwardly led to amidite 5 in multigram amounts. In

• 6-chloro derivative 13 as starting material, easily accessible from deoxyadenosine via enzymatic deamination, acetylation [37] and chlorination. This compound reacted cleanly and yielded 67% of the TEMPO conjugate 14. After deacetylation (15) and tritylation (16), amidite building block 7 was

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• in a MBM. Thiolate displacement reactions of nucleoside derivatives in a MBM. Selenocyanate displacement reactions of nucleoside derivatives in a MBM. Nucleobase glycosidation reactions and subsequent deacetylation performed in a MBM. Regioselective phosphorylation of nicotinamide riboside in a MBM

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• regime in which all of the sugar hydroxy groups have been protected with base-labile groups, most commonly acetate esters. Importantly glycosyl oxazolines are completely stable to the typical basic conditions used for ester removal (e.g., Zemplen deacetylation). The generally accepted approach (until

• , BF3·Et2O and 2,4,6-collidine in dichloroethane, and finally deacetylation. Modifications of this basic strategy have allowed the synthesis of a wide variety of truncated and structurally modified glycans [53][54][55][56][57][58][59]. Amongst other synthetic approaches that may be used to access the

• interconversions, and peracetylation were followed by conversion to the oxazoline, using TMSBr, BF3·Et2O and collidine, and finally deacetylation. It was found that the incorporated azide was tolerated by the ENGase enzyme (Endo A), and so a modified glycoprotein (RNase) was made by enzymatic attachment of this

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

Synthesis and supramolecular properties of regioisomers of mononaphthylallyl derivatives of γ-cyclodextrin

• Markéta Bláhová,
• Sergey K. Filippov,
• Lubomír Kováčik,
• Jiří Horský,
• Simona Hybelbauerová,
• Zdenka Syrová,
• Tomáš Křížek and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2017, 13, 2509–2520, doi:10.3762/bjoc.13.248

•  1) in the presence of the Hoveyda–Grubbs 2nd generation catalyst. After deacetylation, column chromatography afforded the naphthylallyl derivatives in yields between 16–25%, which is comparable to the results of other metathesis reactions of allylated CDs [11][25]. In all cases, only the isomer with

• E configuration of the NA double bond was observed by 1H NMR. Reactions were performed in benzene at 75 °C or dichloromethane at 45 °C, the latter giving lower yields. Prior to the isolation, it was necessary to perform deacetylation of the reaction mixture because the product had the same Rf as the

Synthesis of ergostane-type brassinosteroids with modifications in ring A

• Vladimir N. Zhabinskii,
• Darya A. Osiyuk,
• Yuri V. Ermolovich,
• Natalia M. Chaschina,
• Tatsiana S. Dalidovich,
• Miroslav Strnad and
• Vladimir A. Khripach

Beilstein J. Org. Chem. 2017, 13, 2326–2331, doi:10.3762/bjoc.13.229

• cyclic thiocarbonate 15 as a key reaction step gave the expected Δ2-olefin 16 in an excellent yield (Scheme 2). Subsequent deacetylation of 16 then afforded 24-episecasterol (17). An alternative procedure to Δ2-steroids was applied for the preparation of the B-ring lactone derivative 21 (Scheme 3). The

• mesylation of diol 18 produced dimesylate 19, which was treated with zinc dust and sodium iodide in refluxing DMF (Tipson–Cohen reaction [16]) to give, after deacetylation, B-lactone olefin 21 in 96% yield. 2α,3α- and 2β,3β-epoxides of type 4 and 5 Olefins of type 3 are evident intermediates for the

Enzymatic separation of epimeric 4-C-hydroxymethylated furanosugars: Synthesis of bicyclic nucleosides

• Neha Rana,
• Manish Kumar,
• Vinod Khatri,
• Jyotirmoy Maity and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2017, 13, 2078–2086, doi:10.3762/bjoc.13.205

• sulfonate (TMS-triflate) in acetonitrile yielded the triacetylated nucleoside 8 in 94% yield. Subsequently, deacetylation of acetoxy groups in nucleoside 8 with 2 M NaOH solution in water/dioxane (1:1) also led to the concomitant cylization between suitably placed C-3′-OH and C-1′′-tosyl groups to afford 3

• 95% yield, which on Vorbrüggen coupling with uracil under earlier used base-coupling conditions afforded the corresponding acetylated nucleoside 13 in 92% yield. Subsequent deacetylation of nucleosides 13 followed by concomitant cyclization with 2 M NaOH solution in water/dioxane (1:1) afforded 2′-O

Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 675–693, doi:10.3762/bjoc.13.67

• wall of yeast and fungi [57]. Chitin is also the precursor of chitosan, which is formed by N-deacetylation to partially free amino groups, and is notoriously insoluble in water. Despite this fact, Shchipunov et al. demonstrated in 2015, the first hydrothermal synthesis of CDs derived from chitin in a

Symmetry-based approach to oligostilbenoids: Rapid entry to viniferifuran, shoreaphenol, malibatol A, and diptoindonesin G

• Youngeun Jung,
• Dileep Kumar Singh and
• Ikyon Kim

Beilstein J. Org. Chem. 2016, 12, 2689–2693, doi:10.3762/bjoc.12.266

• quantities of 3-iodobenzofuran 11 in hand, our next task was to elaborate the conversion of 11 to 2,3-diarylbenzofurans (Scheme 4). To this end, 11 was first transformed to aldehyde 13 via 12 through a two-step sequence consisting of deacetylation and Dess–Martin oxidation [39]. To our delight, the

New syntheses of (±)-tashiromine and (±)-epitashiromine via enaminone intermediates

• Darren L. Riley,
• Joseph P. Michael and
• Charles B. de Koning

Beilstein J. Org. Chem. 2016, 12, 2609–2613, doi:10.3762/bjoc.12.256

• -halocarbonyl compounds afforded enaminones 7a and 7b in good yields (90–95%), but the reaction with α-bromoacetonitrile gave enaminonitrile 7c in only 44% yield. The deacetylation of 7a–c with potassium carbonate in methanol afforded the corresponding alcohols 8a–c in good yields (82–89%; Table 1). The data

Facile synthesis of a 3-deazaadenosine phosphoramidite for RNA solid-phase synthesis

• Elisabeth Mairhofer,
• Elisabeth Fuchs and
• Ronald Micura

Beilstein J. Org. Chem. 2016, 12, 2556–2562, doi:10.3762/bjoc.12.250

•  2) [23][24]. Treatment of the 2,6-dichloro-3-deazapurine derivative with ammonia was optimized by Bande et al. recently [25], but still required 200 °C reaction temperature and five days reaction time to afford regioselective displacement of the 2-chlorine atom and concomitant deacetylation in high

Tunable microwave-assisted method for the solvent-free and catalyst-free peracetylation of natural products

• Manuela Oliverio,
• Paola Costanzo,
• Monica Nardi,
• Carla Calandruccio,
• Raffaele Salerno and
• Antonio Procopio

Beilstein J. Org. Chem. 2016, 12, 2222–2233, doi:10.3762/bjoc.12.214

• hydroxy groups are unstable in neutral, slight alkaline or oxidative environments [4]. Furthermore, acetylation is a chemical modification well accepted in a biological environment, being the N-acetylation, N,O-acyl transfer and the deacetylation some of the metabolic processes mediated by cytosolic and

Three-component synthesis of highly functionalized aziridines containing a peptide side chain and their one-step transformation into β-functionalized α-ketoamides

• Lena Huck,
• Juan F. González,
• Elena de la Cuesta and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2016, 12, 1772–1777, doi:10.3762/bjoc.12.166

• of 1,4-diacetyl-2,5-piperazinedione with aldehydes in the presence of potassium tert-butoxide, followed by deacetylation with hydrazine hydrate (see the Supporting Information File 1 for further details). As shown in Scheme 2, treatment of these materials with N-bromosuccinimide and methanol in

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1170–1177, doi:10.3762/bjoc.12.112

• available in excellent yields from the 1,3-diketones 1a and 1b employing aqueous ammonia in the presence of silica gel [21]. Compound 2c was prepared from 1c in 87% yield with ammonium formate [22][23]. Interestingly, treatment of 1c with aqueous ammonia/silica gel failed to give 2c, deacetylation to 1

• -phenylpropan-2-one (76% yield) was observed instead. For the amination of benzyl-substituted diketone 1d both of the above utilized methods failed to provide the desired compound 2d. While treatment with ammonium formate exclusively leads to deacetylation of the starting material to 4-phenylbutan-2-one, the

• reaction with aqueous ammonia/silica gel provided a mixture of the desired compound 2d and the deacetylation product. In both methods slightly acidic reagents are employed, in contrast strictly basic conditions provided by the reaction of 1d with a 7 M solution of ammonia in methanol allowed preparing the