Design, automated synthesis and immunological evaluation of NOD2-ligand–antigen conjugates

• Marian M. J. H. P. Willems,
• Gijs G. Zom,
• Nico Meeuwenoord,
• Ferry A. Ossendorp,
• Herman S. Overkleeft,
• Gijsbert A. van der Marel,
• Jeroen D. C. Codée and
• Dmitri V. Filippov

Beilstein J. Org. Chem. 2014, 10, 1445–1453, doi:10.3762/bjoc.10.148

• attached to the anomeric center of the glucosamine moiety using oxazoline 6 [37][38][39]. Deacetylation and subsequent installation of the benzylidene protective group then gave alcohol 9. Coupling of 9 with (S)-2-chloropropanoic acid in the presence of sodium hydride resulted in the formation of protected

• was removed with Bu3SnH and Pd(PPh3)4 under acidic conditions yielding compound 16 in 72% [42]. For the immunological evaluation of conjugates 2–5 relevant reference compounds are needed, and to this end we assembled MDP derivative 20. On paper, acidic removal of the Boc and benzylidene protecting

• groups in 14 could lead to reference compound 20 in a single step. However, treatment of 14 with a solution of 20% TFA in DCM was accompanied by hydrolysis of the glycosidic linkage. To suppress acid-mediated hydrolysis a stepwise deprotection procedure was followed in which the benzylidene group was

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

• Bernd Schmidt and
• Sylvia Hauke

Beilstein J. Org. Chem. 2014, 10, 1023–1031, doi:10.3762/bjoc.10.102

• better results were obtained with two different phosphine free catalysts comprising a hemilabile alkoxy substituted benzylidene ligand, even at only moderately elevated temperatures. The acrolein cross metathesis product can be converted into the 4-benzoate of L-amicetose via benzoylation, Pd-catalyzed

N-Alkylated dinitrones from isosorbide as cross-linkers for unsaturated bio-based polyesters

• Oliver Goerz and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 902–909, doi:10.3762/bjoc.10.88

• study the course of this cycloaddition the two low molecular model nitrones methyl 3-[benzylidene(oxido)amino]propanoate (3a) and methyl 3-[benzylidene(oxido)amino]butanoate (3b), were prepared from methyl acrylate (2a) and methyl crotonate (2b) with E-benzaldoxime (1) (Scheme 1), respectively. The

• methyl 3-[benzylidene(oxido)amino]propanoate (3a): Methyl acrylate (2a, 0.86 g, 10 mmol) and benzaldoxime (1, 2.42 g, 20 mmol) were placed in a 100 mL round bottom flask and dissolved in 20 mL toluene. Zinc iodide (0.32 g, 1 mmol) and boron triflouride diethyl etherate (0.30 g, 1 mmol) were added. The

• ]. Synthesis of methyl 3-[benzylidene(oxido)amino]butanoate (3b): Methyl crotonate (2b, 1 g, 10 mmol) and benzaldoxime (1, 2.42 g, 20 mmol) were placed in a 100 mL round bottom flask and dissolved in 40 mL toluene. Zinc iodide (0.48 g, 1.5 mmol) and boron triflouride diethyl etherate (0.44 g, 1.5 mmol) were

Efficient carbon-Ferrier rearrangement on glycals mediated by ceric ammonium nitrate: Application to the synthesis of 2-deoxy-2-amino-C-glycoside

• Alafia A. Ansari,
• Y. Suman Reddy and
• Yashwant D. Vankar

Beilstein J. Org. Chem. 2014, 10, 300–306, doi:10.3762/bjoc.10.27

• same reaction with benzylidene or isopropylidene glucals resulted in a complex mixture of products and the desired product was not isolated. Furthermore, the scope of this reaction was extended by subjecting glycals to reactions with other nucleophiles. Thus, glycals 1a and 1b subjected to treatment

A unified approach to the important protein kinase inhibitor balanol and a proposed analogue

• Tapan Saha,
• Ratnava Maitra and
• Shital K. Chattopadhyay

Beilstein J. Org. Chem. 2013, 9, 2910–2915, doi:10.3762/bjoc.9.327

• generation catalyst, benzylidene[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene]dichloro-(tricyclohexylphosphine)ruthenium (25). Pleasingly, the desired cycloalkene 26 was obtained in a gratifying yield of 89%. The sequential removal of the O-acetyl group leading to 27 followed by removal of the N-Boc

IBD-mediated oxidative cyclization of pyrimidinylhydrazones and concurrent Dimroth rearrangement: Synthesis of [1,2,4]triazolo[1,5-c]pyrimidine derivatives

• Caifei Tang,
• Zhiming Li and
• Quanrui Wang

Beilstein J. Org. Chem. 2013, 9, 2629–2634, doi:10.3762/bjoc.9.298

• synthesis of novel [1,2,4]triazolo[1,5-a]pyrimidine derivatives by iodobenzenediacetate (IBD)-mediated oxidative cyclization of suitable N-benzylidene-N′-pyrimidin-2-yl hydrazine precursors, followed by a Dimroth rearrangement [20]. We envisioned that our aldehyde chloropyrimidinylhydrazones 4 would undergo

The total synthesis of D-chalcose and its C-3 epimer

• Jun Sun,
• Song Fan,
• Zhan Wang,
• Guoning Zhang,
• Kai Bao and
• Weige Zhang

Beilstein J. Org. Chem. 2013, 9, 2620–2624, doi:10.3762/bjoc.9.296

• deprotected and oxidized to yield the corresponding aldehyde. Our first step toward this goal was to select appropriate protective groups. Diol 6 was initially converted into benzylidene derivative 8 (α,α-dimethoxytoluene/PPTS/CH2Cl2); 8 was subjected to a regioselective reductive ring-opening reaction [23

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• crude material in the subsequent Knoevenagel condensation with thiazolidinedione 1.68. In order to reduce the intermediate benzylidene double bond in this example sodium borohydride is used in the presence of cobalt chloride efficiently delivering pioglitazone in high purity. Other syntheses of

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• 25); Si: SiMe2Ph, SiMe2Bn (2.0 equiv of 25). Silyl ether synthesis and domino carbopalladation reaction. R,R (Glc): isopropylidene. R,R (Gal): benzylidene. aThe respective equivalents of alkynes 16, glycals 15 and bromine as well as reaction times are given in the Experimental. bThe reaction was

• performed according to entry 5 of Table 1. Derivatisation of anthracycline derivatives. aR,R (Glc): isopropylidene. R,R (Gal): benzylidene. Reactions times: b1.5 h (Glc), 3.5 h (Gal). c1.0 h (Glc), 4.0 h (Gal). d38 h (Glc), 86 h (Gal). e4.0 h (Glc), 3.0 h (Gal). f14 h (Glc), 17 h (Gal). Optimization study

Synthesis of mucin-type O-glycan probes as aminopropyl glycosides

• David Benito-Alifonso,
• Rachel A. Jones,
• Anh-Tuan Tran,
• Hannah Woodward,
• Nichola Smith and
• M. Carmen Galan

Beilstein J. Org. Chem. 2013, 9, 1867–1872, doi:10.3762/bjoc.9.218

• %) to yield final targets 2 and 3 in 60% and 70% yield, respectively (Scheme 1). Access to branched core 2 trisaccharide 4 was accomplished by 4,6-O-benzylidene acetal cleavage from disaccharide 15 using a modified procedure from Chang et al. [21] whereby reaction with p-TsOH in MeOH under sonication

• peracetylated trichloroacetimidate donor 13 in the presence of catalytic TMSOTf. Disaccharide 24 was obtained in 62% yield and without any further protecting-group manipulations, the thioglycoside disaccharide was subsequently activated as a glycosyl donor using NIS/TMSOTf and coupled to 4,6-O-benzylidene

• cleavage of the 4,6-O-benzylidene acetals using p-TsOH in MeOH under sonication followed by removal of the N-Troc groups in the presence of LiOH and subsequent acetylation with pyridine and acetic anhydride formed the desired acetamido functionalities, removal of the ester groups under basic conditions was

Raman spectroscopy as a tool for monitoring mesoscale continuous-flow organic synthesis: Equipment interface and assessment in four medicinally-relevant reactions

• Trevor A. Hamlin and
• Nicholas E. Leadbeater

Beilstein J. Org. Chem. 2013, 9, 1843–1852, doi:10.3762/bjoc.9.215

• )-ethyl 2-benzylidene-3-oxobutanoate (2a, 1.3095 g, 60%) as a clear yellow oil. 1H NMR (CDCl3, 400 MHz) δ ppm 1.26 (t, J = 7.21 Hz, 3H), 2.41 (s, 3H), 4.32 (q, J = 7.09 Hz, 2H), 7.33–7.41 (m, 3H), 7.42–7.47 (m, 2H), 7.56 (s, 1H); 13C NMR (CDCl3, 100 MHz) δ ppm 14.08 (CH3), 26.74 (CH3), 61.92 (CH2), 129.06

• 1608 cm-1 vs concentration of 3-acetyl coumarin (1), yielding a straight line, y = mx + b; m = Raman intensity·M−1 of 1. Monitoring the conversion of benzaldehyde and ethyl acetoacetate to (Z)-ethyl 2-benzylidene-3-oxobutanoate (2a) across a range of reaction conditions (scan time = 15 s, integration

• )-one (4a) across a range of reaction conditions (scan time = 15 s, integration = 10 s). The reaction between salicylaldehyde and ethyl acetoacetate to form 3-acetyl coumarin (1). The Knoevenagel condensation of benzaldehyde and ethyl acetoacetate to yield (Z)-ethyl 2-benzylidene-3-oxobutanoate (2a

Straightforward synthesis of a tetrasaccharide repeating unit corresponding to the O-antigen of Escherichia coli O16

• Manas Jana and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2013, 9, 1757–1762, doi:10.3762/bjoc.9.203

• -benzylidene-2-deoxy-α-D-glucopyranoside (6): Similar as described in [21]. To a solution of compounds 2 (2 g, 5.00 mmol) and 3 (2.5 g, 5.42 mmol) in anhydrous CH2Cl2 (10 mL) was added MS 4 Å (2 g), and the reaction mixture was stirred under an argon atmosphere at room temperature for 30 min. The reaction

• -Methoxyphenyl (6-O-acetyl-2,3,4-tri-O-benzyl-α-D-glucopyranosyl)-(1→3)-(2-O-acetyl-4-O-benzyl-α-L-rhamnopyranosyl)-(1→3)-2-azido-4,6-O-benzylidene-2-deoxy-α-D-glucopyranoside (7): Similar as described in [21]. To a solution of compounds 6 (2 g, 2.95 mmol) and 4 (1.7 g, 3.16 mmol) in anhydrous CH2Cl2/Et2O (10 mL

• ), 62.4 (C-6C), 55.5 (OCH3), 20.8, 20.7 (2 COCH3), 17.3 (CCH3); ESI–MS: 1174.4 [M + Na]+; Anal. calcd for C64H69N3O17: C, 66.71; H, 6.04%; found: C, 66.54; H, 6.20%. p-Methoxyphenyl (2,3,4-tri-O-benzyl-α-D-glucopyranosyl)-(1→3)-(4-O-benzyl-α-L-rhamnopyranosyl)-(1→3)-2-azido-4,6-O-benzylidene-2-deoxy-α-D

Short synthesis of the common trisaccharide core of kankanose and kankanoside isolated from Cistanche tubulosa

• Goutam Guchhait and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2013, 9, 705–709, doi:10.3762/bjoc.9.80

• the presence of borontrifluoride diethyl etherate furnished 2-phenylethyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside (2) in 84% yield [10]. Saponification of compound 2 by using 0.1 M sodium methoxide in methanol followed by benzylidene acetal formation by using benzaldehyde dimethylacetal in the

• = 7.5 Hz, H-1A in the 1H NMR and at δ 101.9 (PhCH), 101.3 (C-1A), 97.4 (C-1B) in the 13C NMR spectra]. Removal of the benzylidene acetal group under neutral conditions by using triethylsilane and Pd/C [15] resulted in the formation of disaccharide diol 7 in 80% yield. NOBF4 catalyzed regio- and

• solvents of adequate purity were used in all reactions. 2-Phenylethyl 4,6-O-benzylidene-β-D-glucopyranoside (5): A solution of compound 2 (5.0 g, 11.05 mmol) in 0.1 M CH3ONa in CH3OH (70 mL) was stirred at room temperature for 3 h and was neutralized with Amberlite IR-120 (H+) resin. The reaction mixture

New simple synthesis of ring-fused 4-alkyl-4H-3,1-benzothiazine-2-thiones: Direct formation from carbon disulfide and (E)-3-(2-aminoaryl)acrylates or (E)-3-(2-aminoaryl)acrylonitriles

• Qiuping Ding,
• Yuqing Lin,
• Guangni Ding,
• Fumin Liao,
• Xiaoyan Sang and
• Yi-Yuan Peng

Beilstein J. Org. Chem. 2013, 9, 460–466, doi:10.3762/bjoc.9.49

• of novel natural-product-like compounds [18][19][20][21][22], we recently reported the practical synthesis of 2-mercapto-4-benzylidene-4H-benzo[d][1,3]thiazines starting from 2-alkynylbenzenamines with CS2, and further transformations to highly functionalized 4-benzylidene-4H-benzo[d][1,3]thiazines

Removal of benzylidene acetal and benzyl ether in carbohydrate derivatives using triethylsilane and Pd/C

• Abhishek Santra,
• Tamashree Ghosh and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2013, 9, 74–78, doi:10.3762/bjoc.9.9

• Abhishek Santra Tamashree Ghosh Anup Kumar Misra Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII-M, Kolkata-700054, India; FAX: 91-33-2355 3886 10.3762/bjoc.9.9 Abstract Clean deprotection of carbohydrate derivatives containing benzylidene acetals and benzyl ethers was

• achieved under catalytic transfer hydrogenation conditions by using a combination of triethylsilane and 10% Pd/C in CH3OH at room temperature. A variety of carbohydrate diol derivatives were prepared from their benzylidene derivatives in excellent yield. Keywords: benzylidene; glycoside; Pd/C; transfer

• hydrogenation; triethylsilane; Introduction Functionalization of carbohydrate intermediates is essential for their assembly towards the synthesis of complex oligosaccharides [1][2][3][4][5][6][7][8][9]. Benzylidene acetal is a frequently used protecting group for the simultaneous protection of 1,2- and 1,3

A new family of four-ring bent-core nematic liquid crystals with highly polar transverse and end groups

• Kalpana Upadhyaya,
• Venkatesh Gude,
• Golam Mohiuddin and
• Rao V. S. Nandiraju

Beilstein J. Org. Chem. 2013, 9, 26–35, doi:10.3762/bjoc.9.4

• , while the central bent core possesses a chloro substituent projected at a location inside the molecular core to represent the transverse dipole. The other end of the molecule is linked to 4-n-alkoxysalicylaldehyde through an imine moiety, which actually seems superior to the benzylidene aniline core and

• molecules overlap. This contributes to the strong attractive interaction between them. The molecule consists of two linkages between the three aromatic fragments, giving an ortho-hydroxy benzylidene moiety, a benzoic acid ester moiety, and a biphenyl residue. The salicylidene linkage instead of the

• unsubstituted benzylidene linkage was preferred due to the presence of the ortho-hydroxy group, which enhances the transverse dipole moment as well as the stability of the imines through intramolecular H-bonding to overcome the hydrolytic instability of the molecules towards moisture. The bent-core platform was

Asymmetric synthesis of γ-chloro-α,β-diamino- and β,γ-aziridino-α-aminoacylpyrrolidines and -piperidines via stereoselective Mannich-type additions of N-(diphenylmethylene)glycinamides across α-chloro-N-sulfinylimines

• Gert Callebaut,
• Sven Mangelinckx,
• Pieter Van der Veken,
• Karl W. Törnroos,
• Koen Augustyns and
• Norbert De Kimpe

Beilstein J. Org. Chem. 2012, 8, 2124–2131, doi:10.3762/bjoc.8.239

• , comparable non-halogenated trans-imidazolidines were already synthesized by 1,3-dipolar cycloaddition of N-benzylidene glycine ester enolates across N-sulfinylaldimines in the presence of a Lewis acid [43]. The trans-stereochemistry of imidazolidine 12b was ensured by the vicinal coupling constant 3JH4-H5

Convergent synthesis of the tetrasaccharide repeating unit of the cell wall lipopolysaccharide of Escherichia coli O40

• Abhijit Sau and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2012, 8, 2053–2059, doi:10.3762/bjoc.8.230

• ]; and (f) preparation of β-D-mannosidic moiety from the β-D-glucoside [13]. Benzylation of 2-azidoethyl 3-O-benzyl-4,6-O-benzylidene-β-D-mannopyranoside (2) [13] (prepared from D-glucose in nine steps) by using benzyl bromide and sodium hydroxide [21] followed by reductive ring opening of the 4,6-O

• -benzylidene acetal with triethylsilane and iodine [22] furnished compound 6 in 82% yield. Stereoselective glycosylation of compound 6 with thioglycoside derivative 3 in the presence of a combination of N-iodosuccinimide (NIS) and HClO4–SiO2 [17] gave disaccharide derivative 7 in a 77% yield. Formation of

• isopropylidene ketal and benzylidene acetal by acid hydrolysis; and finally (d) removal of benzyl ethers by using triethylsilane and 20% Pd(OH)2–C [20] to furnish target compound 1, which was purified through a Sephadex® LH-20 column to give pure compound 1 in 60% overall yield. Spectral data of compound 1

Determination of the relative configuration of tropinone and granatanone aldols by using TBDMS ethers

• Ryszard Lazny,
• Aneta Nodzewska,
• Katarzyna Sidorowicz and
• Przemyslaw Kalicki

Beilstein J. Org. Chem. 2012, 8, 1877–1883, doi:10.3762/bjoc.8.216

• benzaldehyde or elimination to benzylidene derivatives. The behavior of the new isomer under the same isomerization conditions was similar and gave no indications regarding its stereochemical form. It appeared that in this case (as it was for the exo,anti isomer [3]) attempts to convert the presumed exo

• atom at the α-carbon to carbonyl (C-2) is likely responsible for the facile elimination of a water molecule and formation of an isomeric mixture of condensation products ((E) and (Z)-2-benzylidene tropinones) in analogy to the known elimination of acetic acid from the acetyl derivative of the aldol [3

Synthesis and ring openings of cinnamate-derived N-unfunctionalised aziridines

• Alan Armstrong and
• Alexandra Ferguson

Beilstein J. Org. Chem. 2012, 8, 1747–1752, doi:10.3762/bjoc.8.199

• found to be specific for tert-butyl esters, with γ- and δ-benzylidene lactones, methyl, ethyl, phenyl, and benzyl cinnamates all suffering from degradation, presumably via hydrolysis pathways. β-Alkyl-substituted enoates were not explored, and will be the subject of future investigation. A preliminary

Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines

• Chittaranjan Bhanja,
• Satyaban Jena,
• Sabita Nayak and
• Seetaram Mohapatra

Beilstein J. Org. Chem. 2012, 8, 1668–1694, doi:10.3762/bjoc.8.191

• -position of the phenyl ring of the benzylidene moiety, while the enantioselectivity of the reaction decreased if the phenyl ring was substituted with an electron-withdrawing group. The best result, with yields up to 96% and enantioselectivities up to 96%, was obtained in DCM solvent at −40 °C. An

A quantitative approach to nucleophilic organocatalysis

• Herbert Mayr,
• Sami Lakhdar,
• Biplab Maji and
• Armin R. Ofial

Beilstein J. Org. Chem. 2012, 8, 1458–1478, doi:10.3762/bjoc.8.166

• –200 kJ mol–1) Lewis bases. While structurally analogous imidazolylidenes and imidazolidinylidenes have comparable nucleophilicities and Lewis basicities, the corresponding deoxy Breslow intermediates differ dramatically in reactivity. The thousand-fold higher nucleophilicity of 2-benzylidene

• -imidazoline relative to 2-benzylidene-imidazolidine is explained by the gain of aromaticity during electrophilic additions to the imidazoline derivatives. O-Methylated Breslow intermediates are a hundred-fold less nucleophilic than deoxy Breslow intermediates. Keywords: enamine activation; iminium activation

• deoxy Breslow intermediates 45a–f can be described by Equation 1 [107]. In contrast to the situation described for the NHCs in Figure 23, the benzylidene-imidazolines 45a,d are now 103 times more nucleophilic than the corresponding benzylidene-imidazolidines 45c,f (Figure 24 and Figure 25a). The

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

Beilstein J. Org. Chem. 2012, 8, 1374–1384, doi:10.3762/bjoc.8.159

• regenerated (Scheme 11). The following year, Akiyama and co-workers reported another organocatalytic asymmetric synthesis of tetrahydroquinolines using chiral phosphoric acid as the catalyst [25]. In this instance, benzylidene malonates were used as the hydride acceptor. Another important feature of this

Studies on the substrate specificity of a GDP-mannose pyrophosphorylase from Salmonella enterica

• Lu Zou,
• Ruixiang Blake Zheng and
• Todd L. Lowary

Beilstein J. Org. Chem. 2012, 8, 1219–1226, doi:10.3762/bjoc.8.136

• . Results and Discussion Synthesis of 2-methoxy derivative 9 The synthesis of sugar 1-phosphate 9 containing a methyl group at O-2 commenced from 3-O-benzyl-4,6-O-benzylidene-α-D-mannopyranoside 14 [26] as illustrated in Scheme 1. Methylation of the alcohol under standard conditions proceeded in 80% yield

• affording 15. The benzylidene protecting group was cleaved, together with the methyl glycoside, by acetolysis giving the tetra-O-acetylated compound 16 in 81% yield. This glycosyl acetate was converted to the corresponding thioglycoside (17), which was, in turn, coupled with dibenzyl phosphate under NIS

• -benzylidene-α-D-mannopyranoside (19) [26] was first methylated giving 20 and then converted into glycosyl acetate 21 in 49% yield over the two steps. Subsequent thioglycosylation provided a 52% yield of 22. The protected dibenzyl phosphate 23 was next formed by the NIS–AgOTf promoted glycosylation of dibenzyl

Synthesis of 4” manipulated Lewis X trisaccharide analogues

• Christopher J. Moore and
• France-Isabelle Auzanneau

Beilstein J. Org. Chem. 2012, 8, 1134–1143, doi:10.3762/bjoc.8.126

• 12 [56] and 13 [12] (Figure 2). Synthesis of monosaccharide building blocks 8–11 Glucosamine acceptor 8 was prepared in two steps from the known [14] benzylidene 7: the benzylidene acetal was first hydrolyzed, and then the resulting diol (79%) was selectively benzoylated at O-6 (BzCl-collidine