PubMed Health⌕ Search

Biomedical subjects

Luis Castedo

Publications and source records attributed to Luis Castedo.

53 records · Page 3Linked to original sources
PubMed2003

New cyclic peptide assemblies with hydrophobic cavities: the structural and thermodynamic basis of a new class of peptide nanotubes.

A new class of self-assembling peptides based on cyclic peptides made of alternating 3-aminocyclohexanecarboxylic acid (gamma-Acc) and alpha-amino acids is described. The studied cylindrical assemblies are models for a new class of self-assembling peptide nanotubes (SPN) that present the particular property of having the C2 methylene group pointing toward the lumen of the cavity, modifying the properties of the inner surface of the assembly.

Amino Acids, Cyclic↗
PubMed2003

Cyclic allene intermediates in intramolecular dehydro Diels-Alder reactions: labeling and theoretical cycloaromatization studies.

A comprehensive theoretical and experimental investigation of dehydro Diels-Alder reactions examining the evolution of the cyclic allene intermediates under conditions for intramolecular and ionic and radical intermolecular cycloaromatization processes is reported. Theoretical calculations showed that the most favored intramolecular path for cycloaromatization of 1,2,4-cyclohexatriene 4 and its benzoannulated derivative 14, strained cyclic allenes, consists of a pair of successive [1,2] H shifts rather than a [1,5] shift. Cycloaromatization of cyclic allenes may follow both inter- and intramolecular pathways, depending on the experimental conditions (use of protic or aprotic solvents). For synthetic purposes, the best procedure is to use a protic solvent to promote the ionic intermolecular route, the fastest and highest yielding. When the reaction is carried out in CCl4, intermolecular radical addition of chlorine to the cyclic allene competes with intramolecular aromatization paths. Theoretical calculations predict a low barrier for the reaction of cyclic allenes with carbon tetrachloride, and that the cyclic allenes act as nucleophiles in this reaction.

Journal Article↗
PubMed2003

A synthetic miniprotein that binds specific DNA sequences by contacting both the major and the minor groove.

Attachment of a slightly modified basic region of a bZIP protein (GCN4) to a distamycin-related tripyrrole provides a bivalent system capable of binding with high affinity to specific DNA sequences. Appropriate adjustment of the linker between the two units has led to a hybrid that binds a 9 base-pair-long DNA site (TTTTATGAC) with low nanomolar affinity at 4 degrees C. Circular dichroism and gel retardation studies indicate that the binding occurs by simultaneous insertion of the bZIP basic region into the DNA major groove and the tripyrrole moiety into the minor groove of the flanking sequence. Analysis of hybrids bearing alternative linkers revealed that tight, specific binding is strongly dependent on the length and nature of the connecting unit.

Amino Acid Sequence↗
PubMed2002

A sulfinyl-directed asymmetric [5C + 2C] intramolecular acetoxypyranone-alkene cycloaddition.

[reaction: see text] Introduction of a homochiral p-tolylsulfinyl group at the trans terminal position of an alkene induces a total diastereodifferentiation in the intramolecular cycloaddition of the latter to 3-oxidopyrylium ylide precursors. The cycloadducts can be readily desulfinylated to afford enantiomerically pure oxa-bridged bicyclo[5.3.0]decane ring systems. Theoretical calculations confirm that diastereoselectivity stems from the conformational preferences of the alkenylsulfoxide unit in the transition state of the reaction.

Journal Article↗
PubMed2002

Synthesis of eight- and nine-membered carbocycles through a ring-closing metathesis/ring fragmentation strategy: a rapid and versatile approach to bicyclo[6.4.0]- and bicyclo[7.4.0]alkene ring systems.

Ring-closing metathesis (RCM) of cis-2,6-dialkenyl-2-hydroxy-1-cyclohexanones affords bicyclo[3.n.1]alkenones that are easily converted into eight- or nine-membered carbocycles by oxidative cleavage of the keto-bridging tether. Since the starting cyclohexanones are readily assembled from commercially available 1,2-cyclohexanedione, the overall process constitutes a rapid and versatile route to medium-sized carbocycles, which are otherwise difficult compounds to assemble using currently available procedures. If one of the alkenes of the cyclohexanone chains is replaced by an alkyne, the subsequent RCM produces 1,3-diene systems capable of undergoing stereoselective Diels-Alder reaction with activated dienophiles. Oxidative cleavage of the keto bridge of the resulting tricycles leads to 8-6 and 9-6 fused bicarbocycles with up to four stereocenters.

Journal Article↗
PubMed2002

Atom-efficient assembly of 1,5-oxygen-bridged medium-sized carbocycles by sequential combination of a Ru-catalyzed alkyne-alkene coupling and a Prins-type cyclization.

Ruthenium-catalyzed coupling of readily accessible 1-trimethylsilyl-1-alkyn-3-ols to allyl ethyl ether followed by in situ ketalization and Lewis-acid induced cyclization affords 1,5-oxygen-bridged eight- and nine-membered carbocycles, products which are difficult to construct with previously published strategies.

Alkenes↗
PubMed2002

A practical route to enantiopure, highly functionalized seven-membered carbocycles and tetrahydrofurans: concise synthesis of (+)-nemorensic Acid.

Highly diastereoselective thermal [5C+2C] intramolecular pyrone-alkene cycloadditions can be achieved by introducing a homochiral p-tolylsulfinyl group at a suitable position of the alkene. The resulting adducts can be readily desulfinylated to give optically active 8-oxabicyclo[3.2.1]octane derivatives. Interestingly, switching from a sulfinyl to a sulfonimidoyl group allows one to reverse the direction of the diastereofacial selectivity and thereby produces oxa-bridged carbocyclic systems enantiomeric to those obtained from the sulfinyl precursors. Cleavage of the oxa-bridge on the desulfurated adducts yields highly functionalized seven-membered carbocyclic derivatives in enantiopure form. Alternative cleavage of the seven-membered carbocycle provides enantiomerically enriched tetrahydrofurans. We have exploited this reaction pathway for the synthesis of the naturally occurring enantiomer of nemorensic acid.

Journal Article↗
PubMed2001

Design and Synthesis of a Peptide That Binds Specific DNA Sequences through Simultaneous Interaction in the Major and in the Minor Groove This work was supported by the Spanish M.E.C. (PB97-0524) and the Xunta de Galicia (PGIDT00PXI20912PR). M.E.V. and A.M.C. thank the Xunta de Galicia and the University of Santiago for their predoctoral fellowships. We are very grateful to Prof. G. L. Verdine for his input and support in the early phases of this work. We also thank Prof. J. Benavente for allowing us to use the radioactivity facilities and Prof. C. Abell for critical reading of the manuscript.

Explore the source record for details and available documents.

Journal Article↗
PubMed1999

Regioselective Synthesis of Isoquino[1,2-b][3]benzazepines (Homoprotoberberines) through 11-Membered-Ring Stilbene Lactams Obtained by Radical Macrocyclization.

Silylated 11-membered-ring stilbene lactams 3 (E and Z) were easily prepared by intramolecular addition of an aryl radical to a trimethylsilylacetylene. Oxidation of their hindered stilbene double bonds with dioxiranes gave oxidative cleavage of their electron-rich aromatic rings. However, reduction of the amide to an amine functionality in both lactams (E and Z) triggers a regioselective [7,6]-transannular cyclization to isoquino[1,2-b][3]benzazepines (homoprotoberberines).

Journal Article↗
PubMed1999

Dioxirane Epoxidation of 10-Membered-Ring Stilbene Lactams as Synthetic Precursors to Protoberberines.

Silylated stilbene lactams 1, prepared by intramolecular addition of an aryl radical to a trimethylsilylacetylene, were converted into protoberberines by dimethyldioxirane (DMD) epoxidation and subsequent acid-catalyzed cyclization of the epoxysilane with HCl. Treatment of the nonsilylated trans- and cis-stilbene derivatives with DMD afforded 13-hydroxytetrahydroprotoberberines and 13a-hydroxy-13-ketotetrahydroprotoberberines as the main products. Tetrahydroprotoberberines were also obtained in excellent yields by the reaction of both silylated and nonsilylated lactams with hydriodic acid.

Journal Article↗
PubMed1999

Straightforward Construction of Fused 6,7,5-Tricarbocyclic Systems by Tandem [5 + 2]/[4 + 2] Cycloadditions.

One-pot coupling of an intramolecular thermal [5C + 2C] pyrone-alkene cycloaddition to a [4C + 2C] Diels-Alder reaction provides immediate access to 6,7,5-tricarbocyclic systems bearing a 1,4-oxa-bridge in the seven-membered carbocycle. The transformation entails the net formation of four carbon-carbon bonds and creates three new cycles and a minimum of five new stereocenters. Preliminary attempts to open the oxa-bridge by reaction of the adducts with samarium diiodide and trimethylsilyl triflate led to relatively unexpected deoxygenated and aromatized products.

Journal Article↗
PubMed1996

3-Hydroxy-4-pyrones as Precursors of 4-Methoxy-3-oxidopyridinium Ylides. An Expeditious Entry to Highly Substituted 8-Azabicyclo[3.2.1]octanes.

3-Hydroxy-4-pyridones, which are easily prepared from commercially available 3-hydroxy-4-pyrones, can be readily transformed into 4-methoxy-3-oxidopyridinium ylides by treatment with methyl trifluoromethanesulfonate and subsequent deprotonation with a non-nucleophilic base. These ylides are capable of undergoing cycloaddition to several electron-deficient alkenes, thus allowing the synthesis of highly functionalized azabicyclo[3.2.1]octane moieties. The rich substitution patterns of these frameworks might allow their divergent conversion to a variety of natural and non-natural tropane alkaloids.

Journal Article↗
PubMed1996

A Radical Cyclization Approach to Isoindolobenzazepines. Synthesis of Lennoxamine.

The alkaloid lennoxamine (1) was synthesized by transannular cyclization of a 10-membered lactam obtained by intramolecular addition of an aryl radical to a (trimethylsilyl)acetylene. The isoindolo[1,2-b][3]benzazepine skeleton present in lennoxamine was also obtained by means of regioselective 7-endo-trig radical cyclization of methylenephthalimidines.

Journal Article↗
PubMed1996

Synthesis of Antitumor Lycorines by Intramolecular Diels-Alder Reaction.

Pharmacologically interesting lycorines were obtained by a short, efficient method based on an intramolecular Diels-Alder reaction between an alpha-pyrone and an alkyne, followed by loss of CO(2) in a retro Diels-Alder reaction. The cyclization precursors (pyrones 9) were obtained in good yields in two or three steps from the corresponding homophthalic acid or anhydride.

Journal Article↗