Francisco Javier Sardina

Francisco Javier Sardina
University of Santiago de Compostela | USC · Centro Singular de Investigación en Química Biológica y Materiales Moleculares (CIQUS)

PhD Chemistry

About

74
Publications
4,713
Reads
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1,714
Citations
Citations since 2017
4 Research Items
253 Citations
201720182019202020212022202301020304050
201720182019202020212022202301020304050
201720182019202020212022202301020304050
201720182019202020212022202301020304050
Additional affiliations
October 2010 - October 2014
University of Santiago de Compostela
Position
  • Head of Department
October 1988 - present
Universidad de Santiago de Compostela
Position
  • Professor
April 1986 - September 1988
University of California, Berkeley
Position
  • PostDoc Position

Publications

Publications (74)
Article
Bis-enolates with extended π-conjugation, prepared by alkali metal mediated reduction of several aromatic and unsaturated diesters, can be efficiently and regioselectively alkylated with very hindered C-electrophiles, such as neopentyl, secondary and tertiary alkyl halides and tosylates. A one-step synthesis of 4-alkyl phthalates was derived from t...
Article
1,2-Aromatic diesters can be transformed into strained bridged polycyclic structures by a two-step procedure consisting of an initial reductive alkylation promoted by alkaline metals, followed by a reaction of the resulting unsaturated diesters with Me3SnLi. We propose that a stanna-Brook rearrangement plays a fundamental role in the formation of t...
Article
Lithiation reactions of tertiary benzylic esters and carbamates have been studied. Kinetic methodology revealed that a two-step reaction pathway should be considered for these reactions, where either the lithium precomplexation and/or the proton transfer steps can be rate determining. Kinetic isotopic effects were evaluated by comparison of the lit...
Article
A two-step, stereoselective procedure for the synthesis of nine- and ten-membered carbocycles from readily available phthalates is described. A variety of dialkyl phthalates have been transformed into [6,n]-fused bicyclo systems (n = 5, 6, 7) by a dearomatization/cyclization process and then converted into cyclonona- and cyclodecadienes through a b...
Article
Alzheimer's disease is a neurodegenerative pathology with unmet clinical needs. A highly desirable approach to this syndrome would be to find a single lead that could bind to some or all of the selected biomolecules that participate in the amyloid cascade, the most accepted route for Alzheimer disease genesis. In order to circumvent the challenge p...
Article
The complexation of an anionic guest by a cationic water-soluble pillararene is reported. Isothermal titration calorimetry (ITC), 1H NMR, 1H and 19F DOSY, and STD NMR experiments were performed to characterize the complex formed under aqueous neutral conditions. The results of ITC and 1H NMR analyses showed the inclusion of the guest inside the cav...
Article
A series of dibenzo [n.2.2] bicyclic compounds (n = 2-20) were prepared in one step and good yields starting from dimethyl anthracene-9,10-dicarboxylate. Reduction of the aromatic diester using lithium/naphthalene led to a bis-enolate that was cyclized with a variety of bis-electrophiles. The ease of the cyclization is probably due to the puckered...
Article
A one-pot, enantioselective strategy for the dearomatization–annulation of aromatic diesters to give a range of highly functionalized polycyclic molecules with excellent enantioselectivity is presented. This methodology is based on the reaction of bisenolates, prepared by treating aromatic diesters with trialkyltin lithium reagents, which involves...
Article
The first (7Z)-vitamin D analogue, 15, was synthesized stereoselectively using, as the key step, Wittig-Horner coupling between an allylphosphine oxide anion and a α-benzoyloxy ketone. Compound 15 has the same triene system as the putative 7Z intermediate of the mechanism postulated by Okamura and co-workers for thermally induced [1,5]-sigmatropic...
Article
Akfract An efficient (21% overall yield), enantio-and diastereoselective. 11-step synthesis of (lS,2R)-imidazoleglycerol has been developed. The key steps are the stereoselective hydroxyiation of an acyloxazolidinone enolate, the alkylation of a thioester with (MOMOCHz)$uLi and the stereodivergent reduction of the resulting ketone. The scope of the...
Article
(Chemical Equation Presented) Sn-Li exchange equilibria have allowed the quantification of the stabilizing effect of cation-π interactions in organolithium chemistry. Stabilization energy data on the effect of Li-π complexation of an aromatic ring or a C=C double bond in organolithium compounds are presented. The amount of stabilization gained by c...
Article
In our quest for HIV-1 protease inhibitors that are not affected by the V82A resistance mutation, we have synthesized and tested a second generation set of C2-symmetric HIV-1 protease inhibitors that contain a cyclohexane group at P1 and/or P1'. The binding affinity results indicate that these compounds have an improved response to the appearance o...
Article
The kinetics of the hydrolysis of 4-methoxybenzenesulfonyl chloride (MBSC) have been studied in mixed systems made up of surfactant, sodium dodecyl sulfate (SDS) or tetradecyltrimethylammonium bromide (TTABr), and cyclodextrin, beta-CD or SBE-beta-CD(Captisol). The use of SBE-beta-CD instead of beta-CD allowed us to indicate certain characteristics...
Article
A DeltaG(eq) stability scale of secondary alpha-oxy-organolithium compounds was established from measurements of tin-lithium exchange equilibria in THF, and the quantitative effects of substituents at the anionic center on carbanion stability are presented. A new lead-lithium exchange equilibrium reaction was also investigated and shown to be a ver...
Article
Reaction of Me3SnLi with aromatic and heteroaromatic diesters proceeds through a fast stanna-Brook rearrangement that generates an stable bis-enolate which can be regioselectively alkylated and cyclized, in one step, to bicyclic compounds containing 6,5-, 6,6-, and 6,7-fused ring systems.
Article
The easy to use and free available graphical tool MestRe-J, developed for Win-32 platforms, calculates the vicinal proton-proton coupling constants 3J(HH) from the torsion angle phi between the coupled protons for the two kinds of generalized Karplus equations developed by Altona's group as well as for equations from other authors. Besides the clas...
Article
The application of a lossy data compression algorithm based on wavelet transform to 2D NMR spectra is presented. We show that this algorithm affords rapid and extreme compression ratios (e.g., 800:1), providing high quality reconstructed 2D spectra. The algorithm was evaluated to ensure that qualitative and quantitative information are retained in...
Article
[reaction: see text] The reaction of R(3)SnLi with carboxylic acid derivatives proceeds through a novel, very fast stanna-Brook rearrangement that generates alpha-alkoxyorganolithium compounds as intermediates. The outcome of these reactions depends on the nature of the carboxyl derivatives. Reaction of R(3)SnLi with ester derivatives gives rise to...
Article
Magnetic Resonance Companion (MestRe-C) is a software package that offers state-of-the-art facilities for data processing, visualization, and analysis of high-resolution nuclear magnetic resonance (NMR) data, combined with a robust, user-friendly graphical interface that fully exploits the power and flexibility of the Windows platform. The program...
Article
Quantitative thermodynamic stability scales of organolithium compounds can be derived from measurements of tin-lithium exchange equilibria. A DeltaG(eq) scale of alpha-oxy- and alpha-aminoorganolithium compounds was established, and quantitative stabilization effects of O-alkyl, O-alkoxyalkyl, O-carbamoyl, N-carbamoyl, and O-carbonyl groups of the...
Article
A set of secondary N-phenylfluorenyl beta-amino alcohols have been prepared and evaluated as catalysts far the enantioselective addition of diethylzinc to benzaldehyde. The influence of the substituents on the stereogenic centers of the Ligand has been studied, and enantioselectivities up to 97% have been obtained. Those ligands with bulky groups i...
Data
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and...
Article
Methodology for the stereoselective preparation of 3-alkylprolines from N-(9-phenylfluoren-9-yl)-4-oxoproline is presented. The enolate of a N-(9-phenylfluoren-9-yl)-4-oxoproline ester was shown to give stereoselective aldol condensations with aromatic and aliphatic aldehydes. The enolate was preferentially approached by the electrophile through th...
Article
Short, efficient, and stereoselective syntheses of enantiomerically pure C-3- and C-4-alkylated analogues of (2R,3S,4R)-3,4-dihydroxy-2-(hydroxymethyl)pyrrolidine, a potent α-galactosidase inhibitor, from 4-hydroxy-l-proline are presented. Grignard addition or enolate alkylation of a N-(9-phenylfluoren-9-yl)-4-oxo-3-[(methoxymethyl)oxy]proline and...
Article
Enantiomerically pure N-(9-phenylfluoren-9-yl)-α-amino ketones were prepared in excellent yields by acylation of organolithium reagents with N-(9-phenylfluoren-9-yl)-α-amino acid-derived oxazolidinones. The method is not applicable for the acylation of Grignard reagents as they attack the methylenic carbon of the oxazolidinone to give the correspon...
Article
The reaction of methyl N-(9-phenylfluoren-9-yl)pyroglutamate with several organolithium reagents afforded the corresponding ketones in excellent yields and with complete retention of enantiomeric purity. The success of this transformation is due to the unusual stability of the tetrahedral intermediates 5, which stems from two factors: the electron-...
Article
The reaction of di-Me (4S,5S)-I (R = OMe, R1 = 9-phenyl-9-fluorenyl) with several organolithium reagents, RLi, afforded the corresponding enantiomerically pure monoketones I (R = Me, CH2Cl, Bu, Ph, C(OEt):CH2, R1 = 9-phenyl-9-fluorenyl) in good to excellent yields. I (R = CH2Cl, R1 = 9-phenyl-9-fluorenyl) was ultimately transformed into ureido-amid...
Article
Enantiomerically pure N-(9-phenylfluoren-9-yl)-α-amino ketones were prepared in excellent yields by acylation of organolithium reagents with N-(9-phenylfluoren-9-yl)-α-amino acid-derived oxazolidinones. The method is not applicable for the acylation of Grignard reagents as they attack the methylenic carbon of the oxazolidinone to give the correspon...
Article
An efficient (21% overall yield), enantio- and diastereoseleclive, 11-step synthesis of (1S,2R)-imidazoleglycerol has been developed. The key steps are the stereoselective hydroxylation of an acyloxazolidinone enolate, the alkylation of a thioester with (MOMOCH2)2CuLi and the stereodivergent reduction of the resulting ketone. The scope of the react...
Article
We have developed a short, efficient, and stereoselective synthesis of polyhydroxylated pyrrolidine and indolizidine glycosidase inhibitors starting from 4-hydroxy-L-proline. The regio- and stereoselective hydroxylation of an N-Pf-4-oxoproline enolate and the stereoselective reduction of the resulting keto alcohol allowed us to introduce the cis di...
Article
Enantiomerically pure N-(9-phenylfluoren-9-yl) α-amino ketones were prepared by reaction of the N-Pf-alanine-derived oxazolidinone with organolithium reagents. α-Amino ketones thus obtained could be stereoselectively reduced to the corresponding syn or anti β-amino alcohols depending upon the nature of the reducing agent.
Article
We have developed efficient and stereoselective preparations of enantiomerically pure (3R)-and (3S)-N-Pf-3-hydroxy-and N-Pf-3-aminoaspartates by reaction of N-Pf-aspartate enolates with electrophilic hydroxylating or aminating reagents. The stereoselectivity of the hydroxylation and amination reactions was shown to be dependent on the structure of...
Article
A short, efficient and stereoselective synthesis of enantiomerically pure (2R, 3S, 4R) 3,4-dihydroxy-2-hydroxymethylpyrrolidine, a galactosidase inhibitor, from 4-hydroxy-L-proline is presented. The key steps are the regio- and stereoselective hydroxylation of a 4-oxoproline enolate and the stereoselective reduction of the resulting ketoalcohol. An...
Article
We report here a short and efficient synthesis (four steps, 78% overall yield) of dimethyl (2S)-N-(9-phenylfluoren-9-yl)-3,4-didehydroglutamate (1) in enantiomerically pure form from L-glutamic acid. The C-C double bond in 1 was introduced by selective selenenylation-oxidation of dimethyl N-(9-phenylfluoren-9-yl)glutamate. 1 did not undergo loss of...
Article
We report here a short and efficient synthesis (four steps, 78% overall yield) of dimethyl (2,594-(9-phenylfluoren-9-yl)-3,4-didehydroglutamate (1) in enantiomerically pure form from L-glutamic acid. The C-C double bond in 1 was introduced by selective selenenylation-oxidation of dimethyl N-(9-phenylfluoren-9-yl)glutamate. 1 did not undergo loss of...
Article
A chirospecific and stereodivergent synthesis of N-(9-phenylfluorenyl)-3-hydroxyaspartates by hydroxylation of aspartate enolates is described. The stereochemistry of the newly created chiral center is controlled by the nature of the enolate counterion and the ligand coordinating ability of the solvents.
Article
The first (7Z)-vitamin D analogue, 15, was synthesized stereoselectively using, as the key step, Wittig-Horner coupling between an allylphosphine oxide anion and a alpha-benzoyloxy ketone. Compound 15 has the same triene system as the putative 7Z intermediate of the mechanism postulated by Okamura and co-workers for thermally induced [1,5]-sigmatro...
Article
A new synthetic route to the N-protected (+)-anatoxin (VI) is described as outlined in the reaction scheme.
Article
A straightforward and good yielding route to side-chain analogues of the potent neurotoxin and neurotransmitter (+)-anatoxin (1) has been developed. Peroxy acid oxidation of the (silyloxy)butadiene 43 derived from readily synthesized, optically pure (1R)-t-BOC-anatoxin (42) affords silyloxy ketone 44. Fluorolysis of 44 followed by oxidative cleavag...
Article
The optically pure 2,5-difunctionalized homotropane 11, prepared from L-glutamic acid, serves as the common, advanced intermediate for the synthesis of either natural (+)-anatoxin (30, 18% overall yield) or unnatural (-)-anatoxin (33, 30% overall yield) by selective manipulation of either the C-2 ester or C-5 acetyl functionalities. Side-chain subs...
Article
Using biochemical and patch-clamp techniques, we investigated the pharmacology of S- and R-epimers of N-methylanatoxinol, which are analogs of the semi-rigid, stereoselective, nicotinic agonist (+)-anatoxin-a. In contrast to (+)-anatoxin-a, both isomers had poor ability to inhibit the binding of 125I-alpha-bungarotoxin or to open acetylcholine chan...
Article
Improvements in the chirospecific synthesis of (+)-anatoxin from D-glutamic acid have resulted in a process that gives enantiomerically pure material in reproducible 25% overall yield. The major synthetic modifications have been in the decarbonylative iminium ion cyclization and in the introduction of the enone moiety. With multigram quantities of...
Article
The information obtained from two-dimensional NMR and NOED spectroscopy led to the complete structural analysis of five cyclic monoterpenes of marine origin. Correlated 2D spectra allowed the establishment of the gross structural features, the final stereochemical assignments being made by NOEDS. The use of 13C NMR shifts in defining the regio- and...
Article
An efficient synthesis of 25-hydroxyvitamin D2 is described. The chiral center at C-24 was introduced by the stereospecific and regioselective displacement of an allylic carbamate by a cuprate. The triene system was assembled by Horner-Wittig coupling of ketone 13 and the anion of phosphine oxide 14.
Article
A new methodology for structural elucidation of polyhalogenated monoterpenes is presented. It makes extensive use of correlated 2D-NMR and NOEDS and shows that the structures of coccinene and its bromovinyl analog must be corrected to their C-2 epimers.
Article
An efficient, stereospecific synthesis of 25-hydroxy-7,8-dihydroergosterol, starting from the aldehyde (7 steps, 30% overall) was developed. Key steps are the stereospecific displacement of an allylic carbamate by Li2Cu3 (CH3γ5 and the stereoselective reduction of a propargylic ketone by a chiral aluminum complex.
Article
Aus dem Cyclohexadien (Ia) erhält man mit tert.-Butyllithium und Methyliodid das Substitutionsprodukt (Ib); (Ia) und (Ib) werden in die Cyclohexandione (II) übergeführt.

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