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

Convenient synthesis of the pentasaccharide repeating unit corresponding to the cell wall O-antigen of Escherichia albertii O4

• Tapasi Manna,
• Arin Gucchait and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2020, 16, 106–110, doi:10.3762/bjoc.16.12

• -iodosuccinimide (NIS) and perchloric acid supported over silica (HClO4/SiO2) [28][29] furnished disaccharide derivative 8 in 79% yield, which on de-O-acetylation using sodium methoxide [30] gave the disaccharide acceptor 9 in 95% yield. NMR spectral analysis of compound 9 confirmed its formation with appropriate

• -1C), 5.50 (s, PhCH), 4.79 (d, J = 7.5 Hz, H-1B) in 1H NMR and at δ 103.3 (C-1B), 100.8 (PhCH), 99.0 (C-1A), 97.1 (C-1C) in 13C NMR spectra]. Compound 12 was subjected to a set of reactions consisting of a one-pot [32] de-O-acetylation and benzylation using benzyl bromide and sodium hydroxide in the

• subjected to a sequence of reactions consisting of (i) reductive transformation of the azido group into an acetamido group by the treatment with thioacetic acid [34]; (ii) transformation of the N-phthalimido group into acetamido group using hydrazine hydrate followed by selective N-acetylation [35]; (iii

Starazo triple switches – synthesis of unsymmetrical 1,3,5-tris(arylazo)benzenes

• Andreas H. Heindl and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2020, 16, 22–31, doi:10.3762/bjoc.16.4

• . The azobenzene building block 8, with an unsubstituted phenyl ring and two orthogonal nitrogen substituents in the 3- and 5-position (Scheme 3), was prepared. The synthesis commenced with the acetylation of 3,5-dinitroaniline (4) in 95% yield, followed by the selective reduction of one nitro group

SnCl₄-catalyzed solvent-free acetolysis of 2,7-anhydrosialic acid derivatives

• Kesatebrhan Haile Asressu and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2019, 15, 2990–2999, doi:10.3762/bjoc.15.295

• -protected hydroxymethyl group-substituted compound 11 in order to increase its reactivity by reducing the steric hinderance and destabilizing effect of the electron-withdrawing carboxy group at the anomeric center (Scheme 2) [35]. This included a LiBH4 reduction in MeOH and THF, followed by acetylation of

• as catalyst under neat conditions, which provided the expected β-ring-opened product 12 in a moderate yield (Table 1, entry 5). This acetolysis reaction resulted in regioselective acetylation of positions O-7 and O-2 in line with the principles of green chemistry. It is known that anomeric acetates

Chemical synthesis of the pentasaccharide repeating unit of the O-specific polysaccharide from Escherichia coli O132 in the form of its 2-aminoethyl glycoside

• Debasish Pal and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2019, 15, 2563–2568, doi:10.3762/bjoc.15.249

• rhamnosyl donor 3 ensured the formation of the desired 1,2-trans glycoside. Peaks at 4.52 ppm (s, 1H, H-1′) in the 1H NMR and at 98.1 (C-1′) in the 13C NMR spectra confirmed the stereochemistry of the newly formed glycosidic linkage. Further, Zemplén de-O-acetylation [14] gave the disaccharide acceptor 5 in

• the target molecule. First, the phthalimido group was removed using ethylenediamine [26] followed by acetylation with Ac2O in the presence of pyridine [27] to furnish the desired acetamido functionality. Next, the benzylidene group was hydrolyzed using 80% AcOH at 80 ºC [28]. Further, Zemplén de-O

• -acetylation using NaOMe in MeOH followed by hydrogenolysis in a ThalesNano continuous flow hydrogenation assembly using a 10% Pd-C cartridge [29]. After three cycles of hydrogenation, formation of the target pentasaccharide 1 was evident from the mass spectrum (Scheme 4). Conclusion In conclusion, the

Synthesis of novel sulfide-based cyclic peptidomimetic analogues to solonamides

• José Brango-Vanegas,
• Luan A. Martinho,
• Lucinda J. Bessa,
• Andreanne G. Vasconcelos,
• Alexandra Plácido,
• Alex L. Pereira,
• José R. S. A. Leite and
• Angelo H. L. Machado

Beilstein J. Org. Chem. 2019, 15, 2544–2551, doi:10.3762/bjoc.15.247

• anhydride to yield 7. Despite the good results for the acetylation of peptides 6 with R = Me at room temperature, the reaction of the ones with R = n-hexyl needed to be conducted under heat conditions (50 °C). Acidic treatment of the acetates 7 with trifluoroacetic acid: triisopropylsilane decoupling

Indium-mediated C-allylation of melibiose

• Christian Denner,
• Manuel Gintner,
• Hanspeter Kählig and
• Walther Schmid

Beilstein J. Org. Chem. 2019, 15, 2458–2464, doi:10.3762/bjoc.15.238

• unprotected elongated disaccharides in the equilibrium of the pyranoid as well as furanoid isomers in both anomeric forms, respectively. Per-O-acetylation has been performed to facilitate separation of the isomeric mixture for structural identification. The main product revealed to adopt a β-pyranoid form of

• rate. Additionally, intense stirring of the reaction mixture thereby preventing indium powder cluster formation (Table 1, entry 7) turned out to be of advantage for the progress of the reaction. After the allylation subsequent per-O-acetylation gave a mixture of respective epimeric products at position

• -acetylation was conducted leading to a mixture of all four species, indicated by NMR analysis (Scheme 3). In the case of 2-syn the β-pyranose species 5-syn-β was obtained as the main product, besides α-pyranose (5-syn-α) as well as both anomers of the furanoid form (Scheme 4). The overall yield obtained over

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 same methodology was applied in the preparation of (2S,3S)-148. β-Amino acids: (+)-Isoserine ((R)-152) was synthesized from the aziridine ester (2R,1'R)-5b in three simple steps (Scheme 39) [92]. Treatment of (2R,1'R)-5b with acetyl chloride led to N-acetylation with concomitant opening of the

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• ][60]. They have been employed for a number of organic reactions viz., hydrosilylation of aldehydes and ketones, acetylation reactions, redox reactions, oxidative esterification, etc. [61][62][63]. Thus, in concern with increasing demand for sustainable development, a growing number of catalytic

A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12

• Seema V. Kanojia,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2019, 15, 490–496, doi:10.3762/bjoc.15.42

• [47]. Hence, we screened different lipases for the trans-acetylation of (±)-4 for its effective resolution and the results are summarized in Table 1. Based on our past experience in lipase-catalyzed resolution of homoallylic alcohols [38], initially a Novozym 435®-catalyzed acetylation of (±)-4 with

• vinyl acetate in diisopropyl ether (DIP) was attempted. However, the yield and enantioselectivity of the desired alcohol (S)-4 were very poor (Table 1, entry 1). Also the acetylation of (±)-4 with vinyl acetate in diisopropyl ether using Candida rugosa lipase (CRL) and Pseudomonas fluorescens lipase

• , near the optimum temperature of the enzyme (55 °C). Under these conditions, a 50% conversion was achieved within 48 h to obtain both (R)-5 and (S)-4 in 90% ee (Table 1, entry 5). A second acetylation (12% conversion, 20 h) of the resolved (S)-4 under the same conditions improved its ee to 99% (Table 1

Chemical structure of cichorinotoxin, a cyclic lipodepsipeptide that is produced by Pseudomonas cichorii and causes varnish spots on lettuce

• Hidekazu Komatsu,
• Takashi Shirakawa,
• Takeo Uchiyama and
• Tsutomu Hoshino

Beilstein J. Org. Chem. 2019, 15, 299–309, doi:10.3762/bjoc.15.27

• with the acetyl carbonyl carbon. The δH of H-3 in the tetraacetate was shifted downfield by ca. 1.0 ppm (acetylation shift) relative to that in the monoacetate (δH 4.19 → δH 5.37), confirming that the OH group of the FA was acetylated. Consequently, the complete structure of cichorinotoxin tetraacetate

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

• this imide with a reagent obtained from (R)-binaphthol [(R)-BINAL-H] followed by acetylation furnished the triacetate (3R,4S)-111 as a single diastereoisomer after chromatographic purification (Scheme 27). However, its cyanation as described earlier gave a 38:62 mixture of diacetates (3R,4R,5S)-112 and

Unexpected loss of stereoselectivity in glycosylation reactions during the synthesis of chondroitin sulfate oligosaccharides

• Teresa Mena-Barragán,
• José L. de Paz and
• Pedro M. Nieto

Beilstein J. Org. Chem. 2019, 15, 137–144, doi:10.3762/bjoc.15.14

• envisioned the synthetic approach shown in Scheme 1 for the preparation of CS oligosaccharides. Final molecules would be prepared from fully protected precursors by extensive basic hydrolysis followed by selective N-acetylation. The CS chains would be generated by iterative coupling between the disaccharide

• positions 4 and 6 of GalNAc units favor the formation of 1,2-cis glycosidic bonds, even in the presence of 2-participating groups [43][44]. Treatment with (HF)n·Py complex in THF followed by standard acetylation provided compound 7. This derivative displayed a suitable protecting group distribution for the

• heptadecafluoroundecanoyl chloride in the presence of Et3N and catalytic DMAP in a DMF/CH2Cl2 solvent mixture (Scheme 3). Acetylation of the 4-hydroxy group provided disaccharide 10 after F-SPE purification. We planned to employ the final CS oligosaccharides in binding studies to some of the enzymes participating in the

Selective ring-opening metathesis polymerization (ROMP) of cyclobutenes. Unsymmetrical ladderphane containing polycyclobutene and polynorbornene strands

• Yuan-Zhen Ke,
• Shou-Ling Huang,
• Guoqiao Lai and
• Tien-Yau Luh

Beilstein J. Org. Chem. 2019, 15, 44–51, doi:10.3762/bjoc.15.4

• bonds in 7 might adopt cis configuration. Moreover, no norbornene moiety was detected by NMR on the polymeric backbones in 7 (Scheme 7). Since 18 was insoluble in most organic solvents, acetylation of 18 with excess acetic anhydride and pyridine at 70 °C for 10 h gave the corresponding acetate 19, which

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

• 10.3762/bjoc.14.236 Abstract Multistep syntheses of novel 17β-pyrazol-5'-ones in the Δ5-androstane series were efficiently carried out from pregnenolone acetate. A steroidal 17-carboxylic acid was first synthesized as a norpregnene precursor by the bromoform reaction and subsequent acetylation. Its CDI

• multistep sequence (Scheme 1). First compound 1 was converted to the 17β-carboxylic acid 2b by the bromoform reaction and subsequent acetylation according to well-known literature procedures [21][22][23]. After the activation of 2b with 1,1′-carbonyldiimidazole (CDI) as coupling reagent in THF, the

• , a subsequent derivatization with acetic anhydride in pyridine to afford 8, allowed its structure verification indirectly. This derivatization did not only improve the solubility of the compound, but also eliminated the possibility of prototropic tautomerism through acetylation of both the amino and

Tetrathiafulvalene – a redox-switchable building block to control motion in mechanically interlocked molecules

• Hendrik V. Schröder and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2018, 14, 2163–2185, doi:10.3762/bjoc.14.190

• structurally similar rotaxane in which the ammonium station is blocked by N-acetylation shows that the isoxazole moiety acts as a weak second binding station for the wheel. Oxidation of the TTF unit results in Coulombic repulsion between the wheel and the ammonium station which counteracts the energy of

Preparation and X-ray structure of 2-iodoxybenzenesulfonic acid (IBS) – a powerful hypervalent iodine(V) oxidant

• Irina A. Mironova,
• Pavel S. Postnikov,
• Rosa Y. Yusubova,
• Akira Yoshimura,
• Thomas Wirth,
• Viktor V. Zhdankin,
• Victor N. Nemykin and
• Mekhman S. Yusubov

Beilstein J. Org. Chem. 2018, 14, 1854–1858, doi:10.3762/bjoc.14.159

• product of its acetylation Dess–Martin periodinane (DMP) are the most common oxidants used for selective oxidation of alcohols to carbonyl compounds as well as for a variety of other synthetically useful oxidative transformations [10][11]. IBX and DMP are mild oxidants with a relatively low reactivity

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

• 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

• similar way as 13 by enzymatic deamination of adenosine, acetylation [46] and chlorination. A clean reaction with amino-TEMPO compound 10 then produced 78% of compound 18. Ester hydrolysis (19) and tritylation afforded 20 which was silylated with 1.8 equiv of TBS chloride. Although the 3’-silylated and

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• compound 267. Nitro compound 267 was also hydrogenated to produce 7-amino derivative 264. Diazoketone 265 was prepared from 264 with sodium nitrite in fluoroboric acid (HBF4) and its Wolff rearrangement under reflux conditions in water gave 1-hydroxy-2-naphthoic acid (266). Acetylation of 264 with sodium

Synthesis of a sucrose-based macrocycle with unsymmetrical monosaccharides "arms"

• Karolina Tiara,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2018, 14, 634–641, doi:10.3762/bjoc.14.50

• from the C6’-position gave alcohol 22 in 97% yield. Under the same "Swern oxidation–reductive amination–acetylation" conditions, alcohol 22 was converted into aldehyde 23, which reacted further with amine 18, furnishing diolefin 24 in 64% total yield. Cyclization of precursor 24 induced by the Hoveyda

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

• with pectinase from Aspergillus aculeatus, which has both mannosidase and galactosidase activity, at 50 °C for 48 h in a 50 mM acetate buffer (pH 5.0) resulted in the production of a mixture of compounds, from which the Manβ(1–4)Man disaccharide was readily purified by acetylation (typically in ≈30

• donor 2, removed the 4,6-benzylidene, and then regioselectively glycosylated the free primary OH at position 6 with 2,6-branched trisaccharide trichloroacetimidate donor 3. Following conversion of the Troc groups into acetamides and reduction and acetylation of the azide, all of the acetates were

• biantennary glycans. Originally Wang and co-workers reported [92] the synthesis of this type of oxazoline using a sequence of acetylation, treatment with TMSBr/BF3·Et2O/collidine and deacetylation. However, treatment of the free reducing sugar with DMC allows the production of the truncated complex N-glycan

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

• epibrassinolide (2) into the corresponding Δ2-steroids. The first route comprised the selective protection of the side chain diol in 1 and 2 through exhaustive acetylation followed by saponification of the intermediate tetraacetates under controlled conditions [14]. Next, a Corey–Winter reaction [15] of 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

• acetylation methodology has been developed for the separation of an epimeric mixture of ribo- and xylotrihydroxyfuranosides in quantitative yields. The structure of both the monoacetylated epimers, i.e., 5-O-acetyl-4-C-hydroxymethyl-1,2-O-isopropylidene-α-D-ribo- and xylofuranose obtained by enzymatic

• acetylation, has been confirmed by an X-ray study on their corresponding 4-C-p-toluenesulfonyloxymethyl derivatives. Furthermore, the two separated epimers were used for the convergent synthesis of two different types of bicyclic nucleosides, which confirms their synthetic utility. Keywords

• ), diisopropyl ether (DIPE), toluene and dioxane. We carried out all ten sets of reactions for diastereoselective acetylation of epimeric mixtures of ribo- and xylotrihydroxyfuranosides 3a,b by using vinyl acetate at 30, 35, 40 and 45 °C and at 250 rpm in an incubator shaker to evaluate the appropriate lipase

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• (1→4) glycoside.” Indeed, after sequential glycosylation in the presence of TsOH at 50 oC, methanolysis, and per-acetylation, disaccharide 4 was isolated in 20% yield. The authors then very reasonably concluded that “Consequently, the presence of the ester linkage which kept the two sugar moieties in

• debenzylation followed by global acetylation to afford product 30. The extension of this approach to convergent oligosaccharide synthesis and reiterative sequencing in presented in Scheme 8. Thus, maltose and lactose disaccharide building blocks were linked via the xylylene tether, and the resulting compound 31

• that affected the removal of the template and all benzyl protecting groups followed by acetylation of the resulting hydroxy groups. Peptide tether/template Short peptide chains have also been investigated as templates for glycosylation. The general underpinning idea is to streamline the oligosaccharide

Selective enzymatic esterification of lignin model compounds in the ball mill

• Ulla Weißbach,
• Saumya Dabral,
• Laure Konnert,
• Carsten Bolm and
• José G. Hernández

Beilstein J. Org. Chem. 2017, 13, 1788–1795, doi:10.3762/bjoc.13.173

• reported to be effective in yielding new molecules and materials with higher hydrophobicity. However, controlling the degree of acetylation has not been an easy task, with the esterification process often resulting in a mixture of esters or fully esterified samples. In this regard, enzymatic esterification

• , the latter proved less active at catalyzing the esterification of erythro-1a (Table 1, entry 2). This difference in reactivity between both of the lipases has been documented previously in the literature [31]. Comparably, lipase PS-IM, which has been reported to facilitate the acetylation of secondary

• acyl donor, respectively (Table 2, entries 7 and 8). Having determined the best reaction conditions for the selective enzymatic acetylation of the erythro-1a in the ball mill, the protocol was applied to other β-O-4 model compounds (Scheme 3). In general, all the substrates 1a–h generated the