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Papers by Anna Maria Costa Arnau

The Journal of Organic Chemistry, 2013

Additions of lactams, imides, (S)-4-benzyl-1,3-oxazolidin-2-one, 2-pyridone, pyrimidine-2,4-dione... more Additions of lactams, imides, (S)-4-benzyl-1,3-oxazolidin-2-one, 2-pyridone, pyrimidine-2,4-diones (AZT derivatives), or inosines to the electron-deficient triple bonds of methyl propynoate, tert-butyl propynoate, 3-butyn-2-one, Npropynoylmorpholine, or N-methoxy-N-methylpropynamide in the presence of many potential catalysts were examined. DABCO and, secondly, DMAP appeared to be the best (highest reaction rates and E/Z ratios), while RuCl 3 , RuClCp*(PPh 3) 2 , AuCl, AuCl(PPh 3), CuI, and Cu 2 (OTf) 2 were incapable of catalyzing such additions. The groups incorporated (for example, the 2-(methoxycarbonyl)ethenyl group that we name MocVinyl) serve as protecting groups for the above-mentioned heterocyclic CONH or CONHCO moieties. Deprotections were accomplished via exchange with good nucleophiles: the 1dodecanethiolate anion turned out to be the most general and efficient reagent, but in some particular cases other nucleophiles also worked (e.g., MocVinyl-inosines can be cleaved with succinimide anion). Some structural and mechanistic details have been accounted for with the help of DFT and MP2 calculations.

Tetrahedron Letters, 2011

A practical solution to the formation of mixtures of E/Z and open/cyclic isomers in the reaction ... more A practical solution to the formation of mixtures of E/Z and open/cyclic isomers in the reaction Received .......... of (2R,4S)-4-hydroxy-2-methylpentanal (as its hemiacetal, a lactol) with conjugated phosphoranes Revised ........... (stabilised Wittig reagents) and Horner-Wadsworth-Emmons reagents is disclosed. The HWE Accepted ......... reaction has a strong bias to give oxolanes. On the other hand, stabilised Wittig reagents give Available online ...... unsaturated carboxyl derivatives of configuration E (major) and oxolanes (minor); the latter _____________________________ can be avoided by addition of CF 3 CH 2 OH or using morpholine amide phosphorane.

Tetrahedron Letters, 2014

A synthetic approach to palmerolides via Negishi cross coupling. The challenge of the C15-C16 bon... more A synthetic approach to palmerolides via Negishi cross coupling. The challenge of the C15-C16 bond formation

Tetrahedron, 1999

ABSTRACT Hydrolysis of 3′-deoxy-3′-(thymin-1-yl)thymidine, 3′-deoxy-3′-(uracil-1-yl)thymidine, an... more ABSTRACT Hydrolysis of 3′-deoxy-3′-(thymin-1-yl)thymidine, 3′-deoxy-3′-(uracil-1-yl)thymidine, and related furanoses with two nucleobases has been investigated. 3′-β-Substituted analogues, but not the 3′-α-substituted ones, afford isomeric pyranose nucleosides as intermediates, which have been isolated (6c and 6d). Reduction of the hydrolysis products with sodium borohydride afford the corresponding acyclic compounds (2′-deoxy-d-ribitol or d-ribitol derivatives), which have been fully characterised as their peracetates.

The Journal of organic chemistry, Jan 16, 2015

The total synthesis of (-)-amphidinolide K (1) based on asymmetric addition of allylsilane C1-C8 ... more The total synthesis of (-)-amphidinolide K (1) based on asymmetric addition of allylsilane C1-C8 to enal C9-C22 is reported. The 1,9,18-tris-O-TBDPS-ether was converted into the desired 9,18-dihydroxyacid. Its macrolactonization was accomplished by the Shiina method under high-dilution conditions. Compound 1 together with some of its stereoisomers and analogs were subjected to evaluation of the possible disruption of the alpha,beta-tubulin-microtubule and/or G-actin-F-actin equilibria. Compound 1 behaves as a stabilizer of actin filaments (F-actin) in vitro.

Tetrahedron Letters, 1998

The four possible 3'-uracil-l-yl and 3'-thymin-l-yl derivatives of 3'-deoxythymidine and the four... more The four possible 3'-uracil-l-yl and 3'-thymin-l-yl derivatives of 3'-deoxythymidine and the four analogous derivatives of 2'-deoxyuridine have been synthesised from thymidine and uridine, respectively. Advantages of the 2-(methoxycarbonyl)vinyl group to prevent the formation of anhydronueleosides and of SnCI2/PhSH/Et3N in relation to H2/Pd for the reduction of most azido groups are disclosed.

ChemInform, 2003

... The conditions of choice are: catalytic amounts of Et 3 N (only 0.5–1.0 mol%), a reaction tem... more ... The conditions of choice are: catalytic amounts of Et 3 N (only 0.5–1.0 mol%), a reaction temperature around 0°C and, for the less acidic thiols, CF 3 CH 2 OH or CH 3 CN/CF 3 CH 2OH as the solvent. ... (°C), Yield of 2a–i (% Z+E), Z/E ratio. 1, 1a, CF 3 CH 2 OH, 15, 100, 95:5. ...

ChemInform, 2006

Unless specified otherwise, all starting materials and reagents were obtained from commercial sup... more Unless specified otherwise, all starting materials and reagents were obtained from commercial suppliers and used without further purification. All reactions were conducted in oven-dried glassware, under dry nitrogen or argon atmosphere with anhydrous solvents, which were dried and distilled before use according to standard procedures. Solvents used for isolation of products and chromatography were glass distilled. Analytical thin-layer chromatography (TLC) was performed on 0.25 mm silica gel plates (F 254 , Merck). Retention factors (R f) are approximate. Flash column chromatography was performed on SDS silica gel 60 (35-70 µm). 1 H NMR (200 MHz) and 13 C NMR (50.3 MHz) spectra were recorded on a Varian Gemini-200 spectrometer; 1 H NMR (300 MHz) and 13 C NMR (75.4 MHz) spectra were recorded on a Varian 300 Unity Plus spectrometer; 1 H NMR (400 MHz) and 13 C NMR (100.6 MHz) spectra were recorded on a Varian Mercury-400 spectrometer. Chemical shifts (δ) are reported in units of parts per million downfield from tetramethylsilane for 1 H NMR and CDCl 3 (δ 77.0) for 13 C. All coupling constants (J) are reported in hertz; data are reported as follows: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; br, broad. Where necessary, 2D experiments where performed to assist in structure elucidation. Optical rotations ([α] D) were measured on a Perkin-Elmer 241MC polarimeter at 20 ºC. Infrared spectra were recorded on either a Perkin-Elmer 681 or a Nicolet 510-FT spectrometer; only the more representative frequencies are reported (cm-1). Mass spectra were obtained on a HP-5988-A instrument and only the most representative peaks are reported (m/z). High-resolution mass spectra (FAB-HRMS) were obtained by CACTI, Universidade de Vigo. (R)-5-((4-Methoxybenzyloxy)methyl)tetrahydrofuran-2-one (8) * O O PMBO NaH (ca. 60% dispersion in mineral oil, 614 mg, ca. 14 mmol) was added to a solution of (R)-7 (1.1 g, 9.39 mmol) in 7 mL of DMF and 5 mL of THF, under N 2. PMBCl (1.91 mL, 14.1 mmol) was added via syringe and the mixture was stirred for 4 days at room temperature before being quenched with phosphate buffer solution (8 mL). It was then diluted with CH 2 Cl 2 (4 x 50 mL), washed with water (3 x 10 mL) and dried (Na 2 SO 4). The volatiles were removed under reduced pressure and the residue was purified by

Tetrahedron Letters, 2000

A few examples of hybrids/conjugates/chimeras of erythromycin A derivatives and nucleobases (urac... more A few examples of hybrids/conjugates/chimeras of erythromycin A derivatives and nucleobases (uracil and thymine) or thymidine-derived nucleosides are reported. Linkers and reaction conditions have been investigated to avoid the degradation of the macrolide moiety (glycoside hydrolysis, ring cleavage, dehydration, etc.).

Tetrahedron Letters, 2006

Macrolide-nucleoside and macrolide-nucleobase conjugates (chimeras) have been synthesised by link... more Macrolide-nucleoside and macrolide-nucleobase conjugates (chimeras) have been synthesised by linking erythromycin A oxime derivatives and clarithromycin C11,C12-oxazolidinone derivatives with 3 0-amino-3 0-deoxythymidine or adenine through different spacers; clarithromycin-adenine conjugate 16a is the most active species against Micrococcus luteus.

Organic Letters, 2000

A procedure for the conversion of azides to amines, which uses NaBH 4 and catalytic amounts of ti... more A procedure for the conversion of azides to amines, which uses NaBH 4 and catalytic amounts of tin(IV) 1,2-benzenedithiolate, is disclosed. Primary, secondary, tertiary, aromatic, and heteroaromatic azides are reduced in excellent yields under very mild conditions. Reduction of azides to amines is a reaction of paramount importance in organic synthesis; therefore, a great deal of reagents have been reported to effect this transformation. 1 In fact, there has been always considerable interest in searching for more efficient and chemoselective azidereducing agents. 2 Years ago we reported on new tin(II) complexes of the general formula [Et 3 NH][Sn(SR) 3 ], 3 which reduce azides and nitro compounds but not carbonyl groups. Azides, even the most hindered ones, react completely within a few minutes at room temperature in a plethora of solvents, to afford amines in practically quantitative yields. These tin reagents can be readily obtained (i) by adding RSH and Et 3 N to insoluble, polymeric Sn(SR) 2 , 3a,b (ii) by mixing SnCl 2 , RSH, and Et 3 N in a 1:3:3 ratio, 3c and (iii) by treating phos

Organic Letters, 2008

The key C10-C26 fragment in a total synthesis of (-)-amphidinolide E has been prepared from an ox... more The key C10-C26 fragment in a total synthesis of (-)-amphidinolide E has been prepared from an oxolane-containing C10-C17 segment (9, derived from L-glutamic acid) via a Julia-Kocienski reaction with aldehyde 3, followed by a Sharpless AD to obtain the desired diol. The C22-C26 fragment was installed by means of an efficient Suzuki-Molander coupling, with an organotrifluoroborate reagent (4, arising from a cross-metathesis reaction between a vinylboronate and 2-methyl-1,4-pentadiene).

Tetrahedron Letters, 2006

Macrolide-nucleoside and macrolide-nucleobase conjugates (chimeras) have been synthesised by link... more Macrolide-nucleoside and macrolide-nucleobase conjugates (chimeras) have been synthesised by linking erythromycin A oxime derivatives and clarithromycin C11,C12-oxazolidinone derivatives with 3 0-amino-3 0-deoxythymidine or adenine through different spacers; clarithromycin-adenine conjugate 16a is the most active species against Micrococcus luteus.

Organic Letters, 2008

Key dienoic or dienal substructures of cytotoxic macrolides amphidinolide E and dictyostatin have... more Key dienoic or dienal substructures of cytotoxic macrolides amphidinolide E and dictyostatin have been prepared via a Michael addition (followed by elimination of X-) of chiral enolates on-halo derivatives of ethyl acrylate, with full retention of the initial E or Z configuration. Evans oxazolidin-2-ones and our related thiazolidin-2-ones, as well as a fine-tuning of the reaction conditions, have been essential. Many chiral building blocks are accessible from these adducts.

Esta Tesis Doctoral se centra en la preparacion de moleculas con potencial actividad terapeutica,... more Esta Tesis Doctoral se centra en la preparacion de moleculas con potencial actividad terapeutica, dentro del campo de los nucleosidos y las macrolidas. Asi, en el primer capitulo se han preparado 3' -pirimidinilnucleosidos de estructura inedita. Estos se han transformado en carbonucleosidos aciclicos estereoselectivamente. Tambien se ha explorado la ciclacion de acriloilureas en condiciones suaves y en ausencia de agua. El segundo capitulo se ha dedicado a la sintesis de analogos de eritromicina. La preparacion de metileneritromicina no fue factible, en ninguna de las condiciones probadas. EN cambio, se consiguieron sintetizar moleculas hibridas de eritromicina y nucleobases o nucleosidos, con buenos rendimientos, FInalmente, se ha investigado la preparacion de imidatos a partir de lactonas, en el contexto de la quimica de macrolidas. Para ello se estudio la reaccion de lactonas con iminofosforanos y con ciertos complejos de Ti. Mientras que los primeros resultaron serser poco r...

The Journal of organic chemistry, Jan 19, 2014

The use of the 2-(4-methylphenylsulfonyl)ethenyl (tosvinyl, Tsv) group for the protection of the ... more The use of the 2-(4-methylphenylsulfonyl)ethenyl (tosvinyl, Tsv) group for the protection of the NH group of a series of imides, azinones (including AZT), inosines, and cyclic sulfonamides has been examined. The Tsv-protected derivatives are obtained in excellent yields by conjugate addition to tosylacetylene (ethynyl p-tolyl sulfone). The stereochemistry of the double bond can be controlled at will: with only 1 mol % of Et3N or with catalytic amounts of NaH, the Z stereoisomers are generated almost exclusively, while the E isomers are obtained using a stoichiometric amount of DMAP. Analogous phenylsulfonylvinyl-protected groups (with the besvinyl or Bsv group instead of Tsv) are obtained stereospecifically by reaction with (Z)- or (E)-bis(phenylsulfonyl)ethene. For lactams and oxazolidinones, this last method is much better. The Tsv and Bsv groups are stable in the presence of non-nucleophilic bases and to acids. They can be removed highly effectively via a conjugate addition-elimi...

Tetrahedron Letters, 2012

Pd-catalysed reactions of 2-Cl, 2-Br and 2-I derivatives of a 6-chloropurine nucleoside with benz... more Pd-catalysed reactions of 2-Cl, 2-Br and 2-I derivatives of a 6-chloropurine nucleoside with benzamide have been compared, using Pd 2 dba 3 , Xantphos and Cs 2 CO 3 in toluene, between 20 and 80°C. The reactivity order was 2-I > 2-Br > 6-Cl) 2-Cl. The 2-I substituent could be replaced even at 0°C, under conditions disclosed here for the first time. On the other hand, the replacement of the chlorine atom at position 2 (2-Cl) required 110°C.

Tetrahedron Letters, 2004

Reactions of (E)-and (Z)-ketoximes with trialkylphosphines and diphenyl disulfide (PhSSPh) have b... more Reactions of (E)-and (Z)-ketoximes with trialkylphosphines and diphenyl disulfide (PhSSPh) have been compared to gain insight into the mechanisms involved and their potential applications. N-Sulfenylimine isomers and ketimines have been spectroscopically characterised. Both the E and Z isomers of erythromycin A oxime, when treated with Bu 3 P and PhSSPh (1:4:8 ratio), give the same N-phenylsulfenyl ketimine (of configuration E) as the major compound, whereas with Bu 3 P or Me 3 P and PySeSePy (1:8:4 ratio) afford the imine in good yield. Clarithromycin oxime behaves similarly.

The Journal of Organic Chemistry, 2013

Additions of lactams, imides, (S)-4-benzyl-1,3-oxazolidin-2-one, 2-pyridone, pyrimidine-2,4-dione... more Additions of lactams, imides, (S)-4-benzyl-1,3-oxazolidin-2-one, 2-pyridone, pyrimidine-2,4-diones (AZT derivatives), or inosines to the electron-deficient triple bonds of methyl propynoate, tert-butyl propynoate, 3-butyn-2-one, Npropynoylmorpholine, or N-methoxy-N-methylpropynamide in the presence of many potential catalysts were examined. DABCO and, secondly, DMAP appeared to be the best (highest reaction rates and E/Z ratios), while RuCl 3 , RuClCp*(PPh 3) 2 , AuCl, AuCl(PPh 3), CuI, and Cu 2 (OTf) 2 were incapable of catalyzing such additions. The groups incorporated (for example, the 2-(methoxycarbonyl)ethenyl group that we name MocVinyl) serve as protecting groups for the above-mentioned heterocyclic CONH or CONHCO moieties. Deprotections were accomplished via exchange with good nucleophiles: the 1dodecanethiolate anion turned out to be the most general and efficient reagent, but in some particular cases other nucleophiles also worked (e.g., MocVinyl-inosines can be cleaved with succinimide anion). Some structural and mechanistic details have been accounted for with the help of DFT and MP2 calculations.

Tetrahedron Letters, 2011

A practical solution to the formation of mixtures of E/Z and open/cyclic isomers in the reaction ... more A practical solution to the formation of mixtures of E/Z and open/cyclic isomers in the reaction Received .......... of (2R,4S)-4-hydroxy-2-methylpentanal (as its hemiacetal, a lactol) with conjugated phosphoranes Revised ........... (stabilised Wittig reagents) and Horner-Wadsworth-Emmons reagents is disclosed. The HWE Accepted ......... reaction has a strong bias to give oxolanes. On the other hand, stabilised Wittig reagents give Available online ...... unsaturated carboxyl derivatives of configuration E (major) and oxolanes (minor); the latter _____________________________ can be avoided by addition of CF 3 CH 2 OH or using morpholine amide phosphorane.

Tetrahedron Letters, 2014

A synthetic approach to palmerolides via Negishi cross coupling. The challenge of the C15-C16 bon... more A synthetic approach to palmerolides via Negishi cross coupling. The challenge of the C15-C16 bond formation

Tetrahedron, 1999

ABSTRACT Hydrolysis of 3′-deoxy-3′-(thymin-1-yl)thymidine, 3′-deoxy-3′-(uracil-1-yl)thymidine, an... more ABSTRACT Hydrolysis of 3′-deoxy-3′-(thymin-1-yl)thymidine, 3′-deoxy-3′-(uracil-1-yl)thymidine, and related furanoses with two nucleobases has been investigated. 3′-β-Substituted analogues, but not the 3′-α-substituted ones, afford isomeric pyranose nucleosides as intermediates, which have been isolated (6c and 6d). Reduction of the hydrolysis products with sodium borohydride afford the corresponding acyclic compounds (2′-deoxy-d-ribitol or d-ribitol derivatives), which have been fully characterised as their peracetates.

The Journal of organic chemistry, Jan 16, 2015

The total synthesis of (-)-amphidinolide K (1) based on asymmetric addition of allylsilane C1-C8 ... more The total synthesis of (-)-amphidinolide K (1) based on asymmetric addition of allylsilane C1-C8 to enal C9-C22 is reported. The 1,9,18-tris-O-TBDPS-ether was converted into the desired 9,18-dihydroxyacid. Its macrolactonization was accomplished by the Shiina method under high-dilution conditions. Compound 1 together with some of its stereoisomers and analogs were subjected to evaluation of the possible disruption of the alpha,beta-tubulin-microtubule and/or G-actin-F-actin equilibria. Compound 1 behaves as a stabilizer of actin filaments (F-actin) in vitro.

Tetrahedron Letters, 1998

The four possible 3'-uracil-l-yl and 3'-thymin-l-yl derivatives of 3'-deoxythymidine and the four... more The four possible 3'-uracil-l-yl and 3'-thymin-l-yl derivatives of 3'-deoxythymidine and the four analogous derivatives of 2'-deoxyuridine have been synthesised from thymidine and uridine, respectively. Advantages of the 2-(methoxycarbonyl)vinyl group to prevent the formation of anhydronueleosides and of SnCI2/PhSH/Et3N in relation to H2/Pd for the reduction of most azido groups are disclosed.

ChemInform, 2003

... The conditions of choice are: catalytic amounts of Et 3 N (only 0.5–1.0 mol%), a reaction tem... more ... The conditions of choice are: catalytic amounts of Et 3 N (only 0.5–1.0 mol%), a reaction temperature around 0°C and, for the less acidic thiols, CF 3 CH 2 OH or CH 3 CN/CF 3 CH 2OH as the solvent. ... (°C), Yield of 2a–i (% Z+E), Z/E ratio. 1, 1a, CF 3 CH 2 OH, 15, 100, 95:5. ...

ChemInform, 2006

Unless specified otherwise, all starting materials and reagents were obtained from commercial sup... more Unless specified otherwise, all starting materials and reagents were obtained from commercial suppliers and used without further purification. All reactions were conducted in oven-dried glassware, under dry nitrogen or argon atmosphere with anhydrous solvents, which were dried and distilled before use according to standard procedures. Solvents used for isolation of products and chromatography were glass distilled. Analytical thin-layer chromatography (TLC) was performed on 0.25 mm silica gel plates (F 254 , Merck). Retention factors (R f) are approximate. Flash column chromatography was performed on SDS silica gel 60 (35-70 µm). 1 H NMR (200 MHz) and 13 C NMR (50.3 MHz) spectra were recorded on a Varian Gemini-200 spectrometer; 1 H NMR (300 MHz) and 13 C NMR (75.4 MHz) spectra were recorded on a Varian 300 Unity Plus spectrometer; 1 H NMR (400 MHz) and 13 C NMR (100.6 MHz) spectra were recorded on a Varian Mercury-400 spectrometer. Chemical shifts (δ) are reported in units of parts per million downfield from tetramethylsilane for 1 H NMR and CDCl 3 (δ 77.0) for 13 C. All coupling constants (J) are reported in hertz; data are reported as follows: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; br, broad. Where necessary, 2D experiments where performed to assist in structure elucidation. Optical rotations ([α] D) were measured on a Perkin-Elmer 241MC polarimeter at 20 ºC. Infrared spectra were recorded on either a Perkin-Elmer 681 or a Nicolet 510-FT spectrometer; only the more representative frequencies are reported (cm-1). Mass spectra were obtained on a HP-5988-A instrument and only the most representative peaks are reported (m/z). High-resolution mass spectra (FAB-HRMS) were obtained by CACTI, Universidade de Vigo. (R)-5-((4-Methoxybenzyloxy)methyl)tetrahydrofuran-2-one (8) * O O PMBO NaH (ca. 60% dispersion in mineral oil, 614 mg, ca. 14 mmol) was added to a solution of (R)-7 (1.1 g, 9.39 mmol) in 7 mL of DMF and 5 mL of THF, under N 2. PMBCl (1.91 mL, 14.1 mmol) was added via syringe and the mixture was stirred for 4 days at room temperature before being quenched with phosphate buffer solution (8 mL). It was then diluted with CH 2 Cl 2 (4 x 50 mL), washed with water (3 x 10 mL) and dried (Na 2 SO 4). The volatiles were removed under reduced pressure and the residue was purified by

Tetrahedron Letters, 2000

A few examples of hybrids/conjugates/chimeras of erythromycin A derivatives and nucleobases (urac... more A few examples of hybrids/conjugates/chimeras of erythromycin A derivatives and nucleobases (uracil and thymine) or thymidine-derived nucleosides are reported. Linkers and reaction conditions have been investigated to avoid the degradation of the macrolide moiety (glycoside hydrolysis, ring cleavage, dehydration, etc.).

Tetrahedron Letters, 2006

Macrolide-nucleoside and macrolide-nucleobase conjugates (chimeras) have been synthesised by link... more Macrolide-nucleoside and macrolide-nucleobase conjugates (chimeras) have been synthesised by linking erythromycin A oxime derivatives and clarithromycin C11,C12-oxazolidinone derivatives with 3 0-amino-3 0-deoxythymidine or adenine through different spacers; clarithromycin-adenine conjugate 16a is the most active species against Micrococcus luteus.

Organic Letters, 2000

A procedure for the conversion of azides to amines, which uses NaBH 4 and catalytic amounts of ti... more A procedure for the conversion of azides to amines, which uses NaBH 4 and catalytic amounts of tin(IV) 1,2-benzenedithiolate, is disclosed. Primary, secondary, tertiary, aromatic, and heteroaromatic azides are reduced in excellent yields under very mild conditions. Reduction of azides to amines is a reaction of paramount importance in organic synthesis; therefore, a great deal of reagents have been reported to effect this transformation. 1 In fact, there has been always considerable interest in searching for more efficient and chemoselective azidereducing agents. 2 Years ago we reported on new tin(II) complexes of the general formula [Et 3 NH][Sn(SR) 3 ], 3 which reduce azides and nitro compounds but not carbonyl groups. Azides, even the most hindered ones, react completely within a few minutes at room temperature in a plethora of solvents, to afford amines in practically quantitative yields. These tin reagents can be readily obtained (i) by adding RSH and Et 3 N to insoluble, polymeric Sn(SR) 2 , 3a,b (ii) by mixing SnCl 2 , RSH, and Et 3 N in a 1:3:3 ratio, 3c and (iii) by treating phos

Organic Letters, 2008

The key C10-C26 fragment in a total synthesis of (-)-amphidinolide E has been prepared from an ox... more The key C10-C26 fragment in a total synthesis of (-)-amphidinolide E has been prepared from an oxolane-containing C10-C17 segment (9, derived from L-glutamic acid) via a Julia-Kocienski reaction with aldehyde 3, followed by a Sharpless AD to obtain the desired diol. The C22-C26 fragment was installed by means of an efficient Suzuki-Molander coupling, with an organotrifluoroborate reagent (4, arising from a cross-metathesis reaction between a vinylboronate and 2-methyl-1,4-pentadiene).

Tetrahedron Letters, 2006

Macrolide-nucleoside and macrolide-nucleobase conjugates (chimeras) have been synthesised by link... more Macrolide-nucleoside and macrolide-nucleobase conjugates (chimeras) have been synthesised by linking erythromycin A oxime derivatives and clarithromycin C11,C12-oxazolidinone derivatives with 3 0-amino-3 0-deoxythymidine or adenine through different spacers; clarithromycin-adenine conjugate 16a is the most active species against Micrococcus luteus.

Organic Letters, 2008

Key dienoic or dienal substructures of cytotoxic macrolides amphidinolide E and dictyostatin have... more Key dienoic or dienal substructures of cytotoxic macrolides amphidinolide E and dictyostatin have been prepared via a Michael addition (followed by elimination of X-) of chiral enolates on-halo derivatives of ethyl acrylate, with full retention of the initial E or Z configuration. Evans oxazolidin-2-ones and our related thiazolidin-2-ones, as well as a fine-tuning of the reaction conditions, have been essential. Many chiral building blocks are accessible from these adducts.

Esta Tesis Doctoral se centra en la preparacion de moleculas con potencial actividad terapeutica,... more Esta Tesis Doctoral se centra en la preparacion de moleculas con potencial actividad terapeutica, dentro del campo de los nucleosidos y las macrolidas. Asi, en el primer capitulo se han preparado 3' -pirimidinilnucleosidos de estructura inedita. Estos se han transformado en carbonucleosidos aciclicos estereoselectivamente. Tambien se ha explorado la ciclacion de acriloilureas en condiciones suaves y en ausencia de agua. El segundo capitulo se ha dedicado a la sintesis de analogos de eritromicina. La preparacion de metileneritromicina no fue factible, en ninguna de las condiciones probadas. EN cambio, se consiguieron sintetizar moleculas hibridas de eritromicina y nucleobases o nucleosidos, con buenos rendimientos, FInalmente, se ha investigado la preparacion de imidatos a partir de lactonas, en el contexto de la quimica de macrolidas. Para ello se estudio la reaccion de lactonas con iminofosforanos y con ciertos complejos de Ti. Mientras que los primeros resultaron serser poco r...

The Journal of organic chemistry, Jan 19, 2014

The use of the 2-(4-methylphenylsulfonyl)ethenyl (tosvinyl, Tsv) group for the protection of the ... more The use of the 2-(4-methylphenylsulfonyl)ethenyl (tosvinyl, Tsv) group for the protection of the NH group of a series of imides, azinones (including AZT), inosines, and cyclic sulfonamides has been examined. The Tsv-protected derivatives are obtained in excellent yields by conjugate addition to tosylacetylene (ethynyl p-tolyl sulfone). The stereochemistry of the double bond can be controlled at will: with only 1 mol % of Et3N or with catalytic amounts of NaH, the Z stereoisomers are generated almost exclusively, while the E isomers are obtained using a stoichiometric amount of DMAP. Analogous phenylsulfonylvinyl-protected groups (with the besvinyl or Bsv group instead of Tsv) are obtained stereospecifically by reaction with (Z)- or (E)-bis(phenylsulfonyl)ethene. For lactams and oxazolidinones, this last method is much better. The Tsv and Bsv groups are stable in the presence of non-nucleophilic bases and to acids. They can be removed highly effectively via a conjugate addition-elimi...

Tetrahedron Letters, 2012

Pd-catalysed reactions of 2-Cl, 2-Br and 2-I derivatives of a 6-chloropurine nucleoside with benz... more Pd-catalysed reactions of 2-Cl, 2-Br and 2-I derivatives of a 6-chloropurine nucleoside with benzamide have been compared, using Pd 2 dba 3 , Xantphos and Cs 2 CO 3 in toluene, between 20 and 80°C. The reactivity order was 2-I > 2-Br > 6-Cl) 2-Cl. The 2-I substituent could be replaced even at 0°C, under conditions disclosed here for the first time. On the other hand, the replacement of the chlorine atom at position 2 (2-Cl) required 110°C.

Tetrahedron Letters, 2004

Reactions of (E)-and (Z)-ketoximes with trialkylphosphines and diphenyl disulfide (PhSSPh) have b... more Reactions of (E)-and (Z)-ketoximes with trialkylphosphines and diphenyl disulfide (PhSSPh) have been compared to gain insight into the mechanisms involved and their potential applications. N-Sulfenylimine isomers and ketimines have been spectroscopically characterised. Both the E and Z isomers of erythromycin A oxime, when treated with Bu 3 P and PhSSPh (1:4:8 ratio), give the same N-phenylsulfenyl ketimine (of configuration E) as the major compound, whereas with Bu 3 P or Me 3 P and PySeSePy (1:8:4 ratio) afford the imine in good yield. Clarithromycin oxime behaves similarly.