Stereoselective synthesis of chiral furan amino acid analogues of D- and L-serine from D-sugars

The synthesis of chiral furan amino acid analogues of D - and L -serine is reported. The developed methodology starting from D -xylose affords the corresponding amino acid derivative analogue of D -serine enantiomerically pure. Starting from D -arabinose, the corresponding analogue of L -serine was isolated in 92.3% enantio- meric purity. The analogue of D -serine was transformed into a stable Fmoc activated derivative ready to be incorporated into peptides.Ministerio de Educación y Ciencia CTQ2004-00649/BQUEuropean Commission FP6 TRIoH LSHG-CT-2003-503480Junta de Andalucía FQM-34

Exploring architectures displaying multimeric presentations of a trihydroxypiperidine iminosugar

The synthesis of new multivalent architectures based on a trihydroxypiperidine α -fucosidase inhibitor is reported herein. Tetrava- lent and nonavalent dendrimers were obtained by means of the click chemistry approach involving the copper azide-alkyne- catalyzed cycloaddition (CuAAC) between suitable scaffolds bearing terminal alkyne moieties and an azido-functionalized piperi- dine as the bioactive moiety. A preliminary biological investigation is also reported towards commercially available and human glycosidase

Monosaccharides and Analogues from Simple Achiral Unsaturated Compounds

We present herein a selection of ingenious methods that have been developed to convert inexpensive furan, pyrrole and unsaturated hydrocarbons into enantiomerically enriched monosaccharides and analogues of biological interest

Total asymmetric synthesis of monosaccharides and analogues

Since the discovery of the 'formose reaction' by Butlerow,[1] total synthesis of carbohydrates has undergone rapid development. The most important methods for the asymmetric synthesis of monosaccharides and analogues of biological importance are presented. Nowadays any natural and non-natural monosaccharide can be prepared pure in both enantiomeric forms starting from inexpensive starting materials. Metal-based asymmetric catalysis and organocatalysis have been successfully applied, alone or in combination with chemoenzymatic methods. Alternative methods rely upon substrate- or reagent- controlled diastereo- and enantioselective reactions. Suitably protected carbohydrates have been prepared by total synthesis, thus allowing their direct use in the preparation of oligosaccharides and analogues

Syntheses and biological activities of 1,4-iminoalditol derivatives as α-L-fucosidase inhibitors

A review dealing with 1,4-iminoalditol (hydroxylated pyrrolidine) derivatives as inhibitors of α-l-fucosidases including the different synthetic approaches for their preparation as well as their inhibitory properties is presented

Synthesis of Novel 3-Amino(Hydroxy)methyl-l-fuco-Azafagomines as Leads for Selective Inhibitors of α-l-Fucosidases

The synthesis of 3-substituted l-fuco-azafagomines from d-lyxose is reported. They represent the first example of aza-C-glycosides having a biimino (-NH-NH-) moiety. The key step of the synthesis is the introduction of the hydrazine moiety by reductive hydrazination of a 1-deoxy-ketohexose with tert-butyl carbazate. Their glycosidase inhibitory properties are also reported.Ministerio de Ciencia e Innovación of Spain CTQ2008-01565/BQUJunta de Andalucía FQM-345 and P07-FQM-0305

Discovery of a Potent α ‑ Galactosidase Inhibitor by in Situ Analysis of a Library of Pyrrolizidine − (Thio)urea Hybrid Molecules Generated via Click Chemistry

The parallel synthesis of a 26-membered-library of aromatic/aliphatic-(thio)urea-linked pyrrolizidines followed by in situ biological evaluation toward α -galactosidases has been carried out. The combination of the (thio)urea-forming click reaction and the in situ screening is pioneer in the search for glycosidase inhibitors and has allowed the discovery of a potent co ff ee bean α -galactosidase inhibitor (IC 50 = 0.37 μ M, K i = 0.12 μ M) that has also showed inhibition against human lysosomal α -galactosidase ( α -Gal A, IC 50 = 5.3 μ M, K i = 4.2 μ M).Ministerio de Economía y Competitividad (CTQ2016-77270-R)Junta de Andalucía (FQM-345

Synthesis of tri- and tetramines containing two 2,3-dihydroxypyrrolidine moieties and their inhibitory activity toward α-mannosidases

Through the reductive amination of N-[(tert-butoxy)carbonyl]-2,5-dideoxy-2,5-imino-3,4-Oisopropylidene-L-ribose with tetramethylenediamine, hexamethylenediamine, 2,7- diaminofluorene, 4,4'-diaminodiphenylmethane and 1,4-(diaminomethyl)benzene, five tetramines containing two (2R,3R,4S)-2-aminomethylpyrrolidine-3,4-diol moieties have been prepared and assayed for their inhibitory activities toward 24 glycosidases. Tetramines containing the tetramethylene or benzene-1,4-dimethylene linkers are more potent αmannosidase inhibitors than simple (2R,3R,4S)-2-aminomethylpyrrolidine-3,4-diols. Triamines such as (2S,3R,4S)-bis(3,4-dihydroxy-pyrrolidin-2-ethyl)amine were also prepared and shown to be better α-mannosidase inhibitors than (2S,3R,4S)-2-(2-aminoethyl)pyrrolidin-3,4-diol.The Swiss National Science Foundation (grants n° 20-63667.00 and 2100-063567.00/1)European COST (COST D13/0001/99) programOffice Fédéral de l'Education et de la Science (Bern)Dirección General de Investigación Científica y Técnica of Spain (grant n° BQU-2001-3779)SOCRATES (EPFL/Sevilla) progra

Synthesis of tri- and tetramines containing two 2,3-dihydroxypyrrolidine moieties and their inhibitory activity toward α-mannosidases

Through the reductive amination of N-[(tert-butoxy)carbonyl]-2,5-dideoxy-2, 5-imino-3,4-O-isopropylidene-L-ribose with tetramethylenediamine, hexamethylenediamine, 2,7-diaminofluorene, 4,4′-diaminodiphenylmethane and 1,4-(diaminomethyl)benzene, five tetramines containing two (2R,3R,4S)-2- aminomethylpyrrolidine-3,4-diol moieties have been prepared and assayed for their inhibitory activities toward 24 glycosidases. Tetramines containing the tetramethylene or benzene-1,4-dimethylene linkers are more potent α-mannosidase inhibitors than simple (2R,3R,4S)-2-aminomethylpyrrolidine- 3,4-diols. Triamines such as (2S,3R,4S)-bis(3,4-dihydroxy-pyrrolidin-2-ethyl) amine were also prepared and shown to be better α-mannosidase inhibitors than (2S,3R,4S)-2-(2-aminoethyl)pyrrolidin-3,4-diol

Transferring Substituents from Alkynes to Furans and Pyrroles through Heteronorbornadienes as Intermediates: Synthesis of β-Substituted Pyrroles/Furans

The use of 7-oxa/azanorbornadienes as synthetic intermediates for the preparation of 3/4-substituted (β-substituted) furans/pyrroles is presented. The method lies in the inverse electron demand Diels-Alder (iEDDA) cycloaddition between a substituted heteronorbornadiene and an electron-poor tetrazine followed by spontaneous fragmentation of the resulting cycloadduct via two retro-Diels-Alder (rDA) reactions affording a β-substituted furan/pyrrole. The scope of this tandem iEDDA/rDA/rDA reaction was explored in the preparation of 29 heterocycles. A one-pot procedure starting directly from the alkyne precursors of the heteronorbornadiene intermediates is also described.Ministerio de Ciencia e Innovación PID2020-116460RB-100Junta de Andalucía P20-0053