Structure/affinity studies in the bicyclo-DNA series: Synthesis and properties of oligonucleotides containing bc^en-T and iso-tricyclo-T nucleosides

• Branislav Dugovic,
• Michael Wagner and
• Christian J. Leumann

Beilstein J. Org. Chem. 2014, 10, 1840–1847, doi:10.3762/bjoc.10.194

• , quant.; (e) TBAF, THF, rt, 19 h, 95%; (f) thymine, BSA, SnCl4, CH3CN, 0 °C → rt, 17 h, 56% 7β + 22% (7α/β 2.5:1); (g) Bu4NOH, H2O/dioxane, rt, 16 h, 94%; (h) DMTrCl, pyridine, CH2Cl2, rt, 24 h, 98%; (i) CEP-Cl, DIPEA, THF, rt, 4 h, 89%. Conditions: (a) thymine, BSA, TMSOTf, TMSCl, CH3CN, rt, 2.5 h; (b

Convergent synthetic methodology for the construction of self-adjuvanting lipopeptide vaccines using a novel carbohydrate scaffold

• Vincent Fagan,
• Istvan Toth and
• Pavla Simerska

Beilstein J. Org. Chem. 2014, 10, 1741–1748, doi:10.3762/bjoc.10.181

• ) oxide to a solution of glycosyl bromide 2 and hydroxy ester 3, which yielded a mixture of orthoester byproduct 4 and desired glycosylation product 5 (Scheme 2). A catalytic amount of trimethylsilyl trifluoromethanesulfonate (TMSOTf) was added to the mixture, which resulted in ring-opening of orthoester

Concise total synthesis of two marine natural nucleosides: trachycladines A and B

• Haixin Ding,
• Wei Li,
• Zhizhong Ruan,
• Ruchun Yang,
• Zhijie Mao,
• Qiang Xiao and
• Jun Wu

Beilstein J. Org. Chem. 2014, 10, 1681–1685, doi:10.3762/bjoc.10.176

• was synthesized from commercial available 5-deoxy-1,2,3-tri-O-acetyl-β-D-ribofuranose (6) in 8 steps in 43.2% overall yield. Unfortunately, the Vorbrüggen glycosylation of carbohydrate 4 with bis(trimethylsilyl)hypoxanthine with TMSOTf as a catalyst afforded a mixture of inseparable N9 and N7 isomers

• -dichloropurine (18) afforded nucleoside 16 in 86% yield with DBU as a base and TMSOTf as a Lewis acid (Scheme 3). After heated in a pressure tube with ammonia saturated methanol, the benzoyl protecting groups were removed and the chlorine atom at position C6 was substituted at the same time to afford

• , 20% Pd(OH)2/C, Et3N, THF/EtOAc 1:1, rt, 91%; (g) Benzoyl chloride, DMAP (2 equiv), DCM, rt, 92%; (h) Ac2O/AcOH 1:1, H2SO4, rt, 84%. Synthesis of trachycladine B (2). Reagents and conditions: (a) i. N,O-Bis(trimethylsilyl)acetamide (BSA), MeCN; ii. TMSOTf, MeCN, 87%; (b) NH3 sat. methanol, 96%; (c

Bis(β-lactosyl)-[60]fullerene as novel class of glycolipids useful for the detection and the decontamination of biological toxins of the Ricinus communis family

• Hirofumi Dohi,
• Takeru Kanazawa,
• Akihiro Saito,
• Keita Sato,
• Hirotaka Uzawa,
• Yasuo Seto and
• Yoshihiro Nishida

Beilstein J. Org. Chem. 2014, 10, 1504–1512, doi:10.3762/bjoc.10.155

• )-fullerene has been prepared from lactosyl trichloroacetimidate 1 [26] following a pathway as shown in Scheme 1 [25]. The coupling reaction between 1 and 6-chloro-1-hexanol was conducted in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) to yield β-lactoside 2. The nucleophilic substitution

• dichloromethane (30 mL) was stirred for 1 h. After cooling to −40 °C, TMSOTf (53.8 μL, 0.298 mmol) was added to the suspension and the mixture was stirred for another 1 h. After quenching with triethylamine, the reaction mixture was diluted with chloroform and filtered through a Celite pad. The filtrate was

• . Reagents and conditions: (a) 6-chloro-1-hexanol, TMSOTf, CH2Cl2, −40 °C, 1 h, 48%; (b) NaN3, DMF, 60 °C, 16 h, 93%; (c) C60, chlorobenzene, reflux, 7 h, 14%; (d) NaOMe, CH2Cl2, MeOH, 5 h. Distribution (%) of ricin protein (0.1 mg mL−1) after sedimentation in the colloidal suspension of bis-Lac-C60 at

Efficient routes toward the synthesis of the D-rhamno-trisaccharide related to the A-band polysaccharide of Pseudomonas aeruginosa

• Aritra Chaudhury,
• Sajal K. Maity and
• Rina Ghosh

Beilstein J. Org. Chem. 2014, 10, 1488–1494, doi:10.3762/bjoc.10.153

• subsequently serve as the glycosyl donor in the next step. Accordingly, 5 and 6 were coupled almost quantitatively to give 8. The disaccharide so obtained was then coupled with 7 to give the protected trisaccharide 9 in 90% yield using a N-iodosuccinimide-trimethylsilyl trifluoromethanesulfonate (NIS-TMSOTf

• introduced into the reaction mixture at −50 °C after which NIS and TMSOTf were added successively at the same temperature. The temperature was then raised upto −10 °C, and the reaction mixture was stirred for another 1 h at that temperature to give the target trisaccharide as summarized in Scheme 3. At this

• would have similar reactivity towards glycosylative activation. Hence, a preactivation-based glycosylation protocol was devised for the first step leading to the disaccharide 11 using 1-benzenesulfinyl piperidine–triflic anhydride (BSP–Tf2O) [46]. The subsequent step was carried out using NIS–TMSOTf to

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

• . DEVA5K = DEVSGLEQLESIINFEKLAAAAAK. Potency of the NOD2-L antigen conjugates 2–5 in NOD2 transfected HEK cells. DC activation of the conjugates 2–5 and reference compounds 29 and 30. Antigen presentation of the conjugates 2–5 and reference compounds 29 and 30. a) TMSOTf, DCM, 83%; b) cat. NaOMe, MeOH

The Flögel-three-component reaction with dicarboxylic acids – an approach to bis(β-alkoxy-β-ketoenamides) for the synthesis of complex pyridine and pyrimidine derivatives

• Mrinal K. Bera,
• Moisés Domínguez,
• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 394–404, doi:10.3762/bjoc.10.37

• trimethylsilyl trifluoromethanesulfonate (TMSOTf) and triethylamine to provide the bis(4-hydoxypyridines) 16 in 50% yield and 18a in 60% yield, respectively (Scheme 3). A mechanistic proposal for this aldol type condensation has been presented in a previous report [53]. For precursor 14 partial monocyclization

• derivatives like 23b and 24b provided new synthetic options to construct unsymmetrically substituted mixed heteroaromatic systems. As an example we used mono-pyrimidine derivative 24b and cyclized its β-ketoenamide moiety by treatment with TMSOTf and triethylamine. Pyrimidine/pyridinol derivative 26 was

• -ketoenamides to 4-hydroxypyridines (typical procedure 2) Bis(β-ketoenamide) 14 (0.310 g, 0.57 mmol) was placed in an ACE-sealed tube and dissolved in DCE (10 mL). NEt3 (0.40 mL, 2.89 mmol) and TMSOTf (0.50 mL, 2.76 mmol) were added and the resulting mixture was stirred at 90 °C for 3 d. After cooling to rt the

Synthesis of new enantiopure poly(hydroxy)aminooxepanes as building blocks for multivalent carbohydrate mimetics

• Léa Bouché,
• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 213–223, doi:10.3762/bjoc.10.17

• coordination of the lithium cation to the nitrone oxygen is possible. The Lewis acid-induced rearrangements of 1,2-oxazines syn-7, syn-9 and syn-10 were achieved in moderate to good yields using TMSOTf as promoter (Scheme 4). A higher yield of 73% was achieved for the p-bromophenyl derivative 13 (isolated as a

• cooled to −5 °C and TMSOTf (1.35 mL, 7.46 mmol) was slowly added. After 5.5 h stirring at 0 °C, the dark red mixture was quenched with a solution of aq ammonia (5%) turning yellow. Work-up was performed with CH2Cl2 (3 × 30 mL). The combined organic layers were washed with brine, dried with Na2SO4

• skeleton by Lewis acid-induced rearrangement. Conditions: a) 1. TMSOTf, CH2Cl2, −5 °C, 5 to 6 h; 2. aq NH3, rt, 10 min. [TMSOTf = trimethylsilyl trifluoromethanesulfonate] Proposed extended chair-like conformation with Zimmerman–Traxler-type transition state. Synthesis of triols 14, 15 and 16 by reduction

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

• result was obtained upon treatment of the hydroxydioxepane, 3-methoxy-3-methyloctahydro-3H-benzo[c][1,2]dioxepin-9a-ol (179) with TMSOTf/Et3SiH. Thus, the peroxide moiety was not reduced with Et3SiH, and the reaction produced the bicyclic peroxide, 1-methyl-10,11,12-trioxatricyclo[7.2.1.04,9]dodecane

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

• and core 3 disaccharide precursors 14 and 15 were then prepared in the presence of catalytic TMSOTf in respective yields of 90% and 76%. Global deprotection of the assembled oligomers was achieved by a tandem process that required no purifications between steps, as the reactions proceeded cleanly as

• access disaccharide 20b, trichloroacetimidate glycoside donor 12 was reacted with 19 in the presence of catalytic TMSOTf to yield an inseparable mixture of disaccharide product 20a and unreacted starting material. Acetal cleavage with p-TsOH in MeOH under sonication followed by acetylation of the free OH

• and higher α-selectivities than other sialosyl donors [23]. Under our reaction conditions, sialylated disaccharide 22a was prepared as a 3/1 (α/β) mixture using 1-thioadamantyl sialoside 21 as the glycoside donor upon reaction with 19, using NIS in combination with catalytic TMSOTf to activate the

Bioinspired total synthesis of katsumadain A by organocatalytic enantioselective 1,4-conjugate addition

• Yongguang Wang,
• Ruiyang Bao,
• Shengdian Huang and
• Yefeng Tang

Beilstein J. Org. Chem. 2013, 9, 1601–1606, doi:10.3762/bjoc.9.182

• according to the literature methods. First of all, the 1,6-conjugate addition of 3 towards 4 was attempted by employing various conditions, including different basic conditions (NaH, DBU, KHMDS) by activation of the nucleophile 3 or acidic conditions (AcOH, TMSOTf, Sc(OTf)3 and In(OTf)3) by activation of

Synthesis of the tetracyclic core of Illicium sesquiterpenes using an organocatalyzed asymmetric Robinson annulation

• Lynnie Trzoss,
• Jing Xu,
• Michelle H. Lacoske and
• Emmanuel A. Theodorakis

Beilstein J. Org. Chem. 2013, 9, 1135–1140, doi:10.3762/bjoc.9.126

• under Meerwein’s conditions to afford β-ketoester 17. Treatment of 17 with TMSOTf/Et3N followed by enolate alkylation [82] under TBAF/MeI conditions afforded the desired C-5 quaternary center of 18 as a single isomer (35% over four steps). Global reduction of 18 with lithium aluminium hydride produced

Asymmetric synthesis of a highly functionalized bicyclo[3.2.2]nonene derivative

• Toshiki Tabuchi,
• Daisuke Urabe and
• Masayuki Inoue

Beilstein J. Org. Chem. 2013, 9, 655–663, doi:10.3762/bjoc.9.74

• triflate would cause highly unfavorable steric interactions. Indeed, the cycloaddition between 7 and acrolein proceeded even at −78 °C by the action of TMSOTf (50 mol %) in toluene to afford the bicyclo[3.2.2]nonene 8 and 20 along with a small amount of two other isomers 21ab (Table 1, entry 1). Among the

• various silyl triflates used (Table 1, entries 1–3), TBSOTf was found to be superior to TMSOTf or TIPSOTf in terms of the combined yield. Alteration of the amount of TBSOTf from 50 mol % (Table 1, entry 2) to 200 mol % (Table 1, entry 4) and change of the solvent from toluene (Table 1, entry 4) to CH2Cl2

• ), 9.37 (1H, d, J = 5.0 Hz, CHO); 13C NMR (125 MHz, CDCl3) δ −4.8, −4.2, 18.1, 24.1, 25.9, 29.7, 33.8, 34.1, 34.6, 38.0, 41.8, 50.6, 73.5, 134.1, 142.4, 204.3; HRMS–ESI (m/z): [M + Na]+ calcd for C18H32O2SiNa, 331.2064; found, 331.2057. Oxime 24: TMSOTf (220 μL, 1.2 mmol) was added to a solution of 8 (122

Synthesis and stability study of a new major metabolite of γ-hydroxybutyric acid

• Ida Nymann Petersen,
• Jesper Langgaard Kristensen,
• Christian Tortzen,
• Torben Breindahl and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2013, 9, 641–646, doi:10.3762/bjoc.9.72

• Information File 1). After heating at 90 °C for 72 h GBL starts to form at low concentration (indicated with arrows). Schmidt glucuronidation [11] with trichloroacetimidate 3. Synthesis of 4 and 5 using acceptors 7 and 8 was attempted several times by using BF3·OEt2, 3 Å MS, CH2Cl2, −20 °C to rt, and TMSOTf

Glycosylation efficiencies on different solid supports using a hydrogenolysis-labile linker

• Mayeul Collot,
• Steffen Eller,
• Markus Weishaupt and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 97–105, doi:10.3762/bjoc.9.13

• using five equivalents of the building block each time or were carried out three times by using three equivalents of the building block each time. Glycosyl trichloroacetimidate 34 was activated by catalytic amounts of trimethylsilyl trifluoromethanesulfonate (TMSOTf) at −15 °C in dichloromethane or

• ; 5. p-TsOH·H2O, MeOH, DCM, rt. Model glycosylation by using an automated oligosaccharide synthesizer. Reactions and conditions: (a) 34, TMSOTf, DCM, −15 °C (30 min); (b) 35, NIS, TfOH, DCM, dioxane, different temperatures and reaction times; (c) Pd(OAc)2, HCOONH4, H2O; (d) NaOMe, MeOH, DCM, rt

• . Glycosylation of 34 to linker 23 and subsequent Staudinger reduction of the azide. Reactions and conditions: (a) TMSOTf, DCM, −15 °C, 30 min; (b) PMe3, NEt3, H2O, THF, 25 °C, 30 min; (c) NaOMe, MeOH, DCM, rt. Functionalization of different resins with linker 1 and loading determination. Supporting Information

Synthesis of a derivative of α-D-Glcp(1->2)-D-Galf suitable for further glycosylation and of α-D-Glcp(1->2)-D-Gal, a disaccharide fragment obtained from varianose

• Carla Marino,
• Carlos Lima,
• Karina Mariño and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2012, 8, 2142–2148, doi:10.3762/bjoc.8.241

• in Et2O, employing TMSOTf as catalyst, proceeded with complete regio- and stereoselectivity, affording the α-glycosylaldonolactone 5 in 79% yield (Scheme 1). The α-anomeric configuration and the regioselectivity of the glycosylation were confirmed on the basis of the NMR spectra. In the 1H NMR

• (1.28 g, 1.88 mmol), 5,6-O-isoprolyliden-D-galactono-1,4-lactone (4, 0.48 g, 2.24 mmol) [16] and 4 Å powdered molecular sieves (0.5 g) in anhydrous Et2O (12 mL) was cooled to −78 °C, and TMSOTf (0.11 mL, 0.62 mmol) was slowly added. After 48 h of stirring at 5 °C, the mixture was quenched by addition of

Acylsulfonamide safety-catch linker: promise and limitations for solid–phase oligosaccharide synthesis

• Jian Yin,
• Steffen Eller,
• Mayeul Collot and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2012, 8, 2067–2071, doi:10.3762/bjoc.8.232

• activated by TMSOTf were conducted, and followed by Zemplén cleavage. Similarly, three equivalents of thioglycosides 17 and 19 were added three times (triple coupling) for each glycosylation employing DMTST or NIS/TfOH as an activator. In both instances, surprisingly, only N-glycoside 20 (minor product) and

Imidazolinium and amidinium salts as Lewis acid organocatalysts

• Oksana Sereda,
• Nicole Clemens,
• Tatjana Heckel and
• René Wilhelm

Beilstein J. Org. Chem. 2012, 8, 1798–1803, doi:10.3762/bjoc.8.205

• TMSOTf gave the product in 55% yield. In both cases the endo product was the major product. The reaction was followed by TLC and the temperature was gradually increased from –10 to 45 °C over 4 days in ca. 10 °C steps. Next, imidazolinium salt 7 [25] was used in the reaction. The formation of the product

Automated synthesis of sialylated oligosaccharides

• Davide Esposito,
• Mattan Hurevich,
• Bastien Castagner,
• Cheng-Chung Wang and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2012, 8, 1601–1609, doi:10.3762/bjoc.8.183

• was the glycosylation of compound 14 with building block 4 (Scheme 2), which proceeded efficiently in the presence of trimethylsilyl triflate (TMSOTf) as promoter at −10 °C to afford trisaccharide 15 with a yield of 80%. It is worth mentioning that glycosylation of an analogue of glucose 14 equipped

• glycosylation with building block 4 (2 × 5 equiv) for 1 h at −10 °C with TMSOTf used for activation. Radical reduction using tributyltinhydride and azobisisobutyronitrile (AIBN) was performed to convert the trichloroacetamide into an N-acetyl moiety, followed by methoxide-mediated cleavage to provide compound

• three steps for 4 (for a detailed description of the synthesis of compound 4 see the supporting information of [5]); 62% over three steps for 5. Reagents and conditions. (i) TMSOTf, DCM, −10 °C, 80%; (ii) NaOMe, MeOH; then KOH, MeOH, 60 °C; then Pd/C, H2, AcOH, MeOH, THF, H2O, rt, 76% over three steps

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

• intermediates 26–28 is described in Scheme 2. First, acceptors 23–25 were prepared in good yields through the selective removal of the chloroacetate (thiourea) in disaccharides 20–22. Fucosylation of acceptor 23 with ethylthioglycoside 12 was first attempted under NIS and TMSOTf activation at low temperature

An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

• Grazia Marano,
• Claas Gronewold,
• Martin Frank,
• Anette Merling,
• Christian Kliem,
• Sandra Sauer,
• Manfred Wiessler,
• Eva Frei and
• Reinhard Schwartz-Albiez

Beilstein J. Org. Chem. 2012, 8, 787–803, doi:10.3762/bjoc.8.89

• reagents and anhydrous solvents were used without further purification unless stated otherwise. TMSOTf was from Acros, Geele, Belgium, all other chemicals were from either Sigma-Fluka, Taufkirchen, Germany, Fisher Scientific, Schwerte, Germany or Merck Schuchardt, Darmstadt, Germany. Thin-layer

• ]. For 3,4-bis{[(2,3,4,6-tetra-O-benzoyl-β-D-galactopyranosyl)oxy]methyl}furan (6) TMSOTf (100 µL) was added to a solution of furan 1 (1.28 g, 10 mmol) and imidate 2 (18.5 g, 25.0 mmol) in dry CH2Cl2 (150 mL) at −40 °C. The reaction was stirred for 2 h at 0 °C and then extracted with aq. NaHCO3 (100 mL

• C1´), 124.83 (C3, C4), 148.07 (C2, C5). Synthesis of (4-{[(β-D-galactopyranosyl)oxy]methyl}furan-3-yl)methyl hydrogen sulfate (GSF, 5): 3-Hydroxymethyl-4-{[(2,3,4,6-tetra-O-benzoyl-β-D-galactopyranosyl-1-yl)-oxy]methyl}furan (3) was synthesized by adding TMSOTf (100 µL) to an ice cooled solution of

2-Allylphenyl glycosides as complementary building blocks for oligosaccharide and glycoconjugate synthesis

• Hemali D. Premathilake and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2012, 8, 597–605, doi:10.3762/bjoc.8.66

• oxygen, similarly to that known for O-pentenyl glycosides [30]. It is possible that the activation of the AP leaving group can also be achieved with TMSOTf or BF3·Et2O via the direct anomeric activation pathway, which was expected to become the key feature of the AP-mediated glycosylation approach in

• range of standard glycosyl acceptors 2–5 [18]. Encouragingly, the reaction of glycosyl donor 1a with the primary glycosyl acceptor 2 in the presence of TMSOTf was completed within 15 min and provided the corresponding disaccharide 6a in 82% yield (Table 1, entry 1). As expected, when a control

• experiment was set up with MeOTf, no glycosylation of 2 took place (Table 1, entry 2). The fact that the AP group in 1a can be activated with TMSOTf, but not with MeOTf, offers a basis for exploring its orthogonality to thioglycosides. This is because thioglycosides show a completely opposite reactivity

Dependency of the regio- and stereoselectivity of intramolecular, ring-closing glycosylations upon the ring size

• Patrick Claude,
• Christian Lehmann and
• Thomas Ziegler

Beilstein J. Org. Chem. 2011, 7, 1609–1619, doi:10.3762/bjoc.7.189

• –d, to give the corresponding 2-[3-(alkylcarbamoyl)propionyl] tethered saccharides 5a–d. Intramolecular, ring closing glycosylation of the saccharides with NIS and TMSOTf afforded the tethered β(1→3) linked disaccharides 6a–c, the α(1→3) linked disaccharides 7a–d and the α(1→2) linked disaccharide 8d

• the benzylidene group was observed under these conditions. Compound 3b has not been described in the literature so far. It was prepared by first glucosylating 4-(benzyloxycarbonylamino)butanol [34] with 2,3,4,6-tetra-O-benzoyl-α-D-glucopyranosyl trichloroacetimidate [35] (cat. TMSOTf, CH2Cl2, −10 °C

• were intramolecularly glycosylated by activating the phenylthio group with the NIS-TMSOTf reagent (Scheme 1) [37]. Attention had to be paid to the choice of solvent, because the tethered glycosides 5 were only poorly soluble in most solvents that are usually applied for glycosylations with

A practical two-step procedure for the preparation of enantiopure pyridines: Multicomponent reactions of alkoxyallenes, nitriles and carboxylic acids followed by a cyclocondensation reaction

• Christian Eidamshaus,
• Roopender Kumar,
• Mrinal K. Bera and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2011, 7, 962–975, doi:10.3762/bjoc.7.108

• , we reported a new synthesis of pyridines based on the trimethylsilyl trifluoromethanesulfonate (TMSOTf) induced cyclocondensation reaction of β-ketoenamides [29][30][31][32][33][34]. This cyclocondensation step can be rationalized as a 6π-electrocyclization of the disilylated intermediate 5 to

• cyclocondensation must be induced or completed by treatment with TMSOTf and an amine base in a suitable solvents at elevated temperatures. In order to minimize the operational effort, the process can be performed as quasi-one-pot procedure without purification of the intermediary β-ketoenamide. Scope and

• due to alternative hydrogen bond formation with the NH unit to the pyridine nitrogen rather than to the carbonyl group. Subsequent cyclocondensation with TMSOTf and NEt3 in 1,2-dichloroethane gave the expected pyridine derivatives, which were directly converted into pyrid-4-yl nonaflates in a second

Synthesis, reactivity and biological activity of 5-alkoxymethyluracil analogues

• Lucie Brulikova and
• Jan Hlavac

Beilstein J. Org. Chem. 2011, 7, 678–698, doi:10.3762/bjoc.7.80

• 84 was prepared by a previously described procedure [23]. Next 5-bromovinyluracil (BVUr) was silylated and reacted with 84 in the presence of TMSOTf as the Lewis acid. This was followed by deacetylation with anhydrous K2CO3 in MeOH to provide the di-O-benzylated nucleoside 85 in 73% yield. For the

• analogues 124f–i afforded 5-[alkoxy(4-nitrophenyl)methyl]uridines 126f–i and 127f–i (Scheme 22) [35]. In a first step, the alkoxy uracils 124 were silylated and then reacted with a protected ribose in the presence of TMSOTf to afford diastereomeric mixtures of nucleosides 125. Diasteroisomers were separated