María M. Zurbano

Enantioselective synthesis of (S)- and (R)-α-methylserines: application to the synthesis of (S)- and (R)-N-Boc-N,O-isopropylidene-α-methylserinals

Abstract This report describes the synthesis of enantiomerically pure ( S )- and ( R )-α-methylserines on a multigram scale, starting from the Weinreb amide of 2-methyl-2-propenoic acid and using a stereodivergent synthetic route that involves a Sharpless asymmetric dihydroxylation reaction. As a synthetic application of these quaternary α-amino acids, they were used as starting materials in the synthesis of the well-known valuable homochiral ( S )- and ( R )- N -Boc- N , O -isopropylidene-α-methylserinal building blocks.

Asymmetric synthesis of all isomers of α-methyl-β-phenylserine

Abstract This report describes the synthesis of enantiomerically pure (2 R ,3 R )-, (2 R ,3 S )-, (2 S ,3 S )- and (2 S ,3 R )-2-amino-3-hydroxy-2-methyl-3-phenylpropanoic acids, four quaternary α-amino acids, using a stereodivergent synthetic route and starting from ( S )- and ( R )- N -Boc- N , O -isopropylidene-α-methylserinals. The key step involves the asymmetric Grignard additions to the above chiral aldehydes, in which high levels of asymmetric induction are observed.

A straightforward synthesis of both enantiomers of α-vinylalanine and α-ethynylalanine

Abstract This report describes the synthesis of enantiomerically pure ( S )- and ( R )-α-vinylalanines and ( S )- and ( R )-α-ethynylalanines, four quaternary α-amino acids, using a straightforward synthetic route and starting from ( S )- and ( R )- N -Boc- N,O -isopropylidene-α-methylserinals.

S-Michael Additions to Chiral Dehydroalanines as an Entry to Glycosylated Cysteines and a Sulfa-Tn Antigen Mimic

Stereoselective sulfa-Michael addition of appropriately protected thiocarbohydrates to chiral dehydroalanines has been developed as a key step in the synthesis of biologically important cysteine derivatives, such as S-(β-D-glucopyranosyl)-D-cysteine, which has not been synthesized to date, and S-(2-acetamido-2-deoxy-α-D-galactopyranosyl)-L-cysteine, which could be considered as a mimic of Tn antigen. The corresponding diamide derivative was also synthesized and analyzed from a conformational viewpoint, and its bound state with a lectin was studied.

Synthesis of enantiopure (αMe)Dip and other α-methylated β-branched amino acid derivatives

Abstract This report describes the synthesis of the two enantiomerically pure α-methylated β-branched phenylalanine derivatives, (S)- and (R)-α-methyl-β,β-diphenylalanine—(αMe)Dip—starting from the chiral building blocks (R)- and (S)-N-Boc-N,O-isopropylidene-α-methylserine methyl esters, respectively. The key step involves a double alkylation with a Grignard reagent on an ester group. The use of the same protocol for the preparation of other α-methylated β-branched serine derivatives is also described.

Asymmetric synthesis of meso- and (2R,4R)-2,4-diaminoglutaric acids

Abstract In order to synthesize meso- and (2 R ,4 R )-2,4-diaminoglutaric acids, a synthetic route has been developed starting from Garners aldehyde and where the key steps are the asymmetric hydrogenations of ( E )- and ( Z )-( R )-3- tert -butoxycarbonyl-2,2-dimethyl-4-[2′-(benzamido)-2′-(methoxycarbonyl)ethenyl]-1,3-oxazolidine, under heterogeneous conditions, followed by oxidation and further hydrolysis. A model is proposed to explain the stereochemical outcome of the asymmetric hydrogenation.

An alternative approach to (S)- and (R)-2-methylglycidol O-benzyl ether derivatives

Abstract This report describes the gram scale synthesis of ( S )- and ( R )-2,2,4-trimethyl-4-(hydroxymethyl)-1,3-dioxolanes using the Sharpless asymmetric dihydroxylation (AD) of the Weinreb amide of 2-methyl-2-propenoic acid. The 2-methylglycerol acetonides resultant from protection of the AD products were used as starting materials in the synthesis of O -benzyl ethers of the valuable C4-chiral building blocks ( S )- and ( R )-2-methylglycidol.

A Biomimetic Approach to Lanthionines

The asymmetric sulfa-Michael additions of appropriately protected L- and D-cysteine derivatives to new chiral dehydroamino acid derivatives have been developed as key steps in the synthesis of biologically important cysteine derivatives, such as lanthionine (Lan) and β-methyllanthionine (MeLan), which are unusual bis-α-amino acids found in the emerging lantibiotics such as nisin.

A Double Diastereoselective Michael-Type Addition as an Entry to Conformationally Restricted Tn Antigen Mimics

A totally stereocontrolled C-Michael addition of serine-equivalent C-nucleophiles to tri-O-benzyl-2-nitro-d-galactal was used as the key step to synthesize several pyrano[3,2-b]pyrrole structures. These scaffolds could be regarded as conformationally restricted Tn antigen mimics, as we have demonstrated by biological assays. The pyranose rings retain their (4)C1 chair conformation, as shown by molecular modeling and NMR spectroscopy. The expected bioactivity was established by a competition-tailored enzyme-linked lectin assay using both soybean and Vicia villosa agglutinins as model lectins. The facile described synthetic route and the strategic combination of computational and experimental techniques to reveal conformational features and bioactivity demonstrate the prepared glycomimics to be promising candidates for further exploitation of this scaffold to give glycans for lectin blocking and vaccination.

Synthesis of meso-2,4-diaminoglutaric acid.

Abstract In order to synthesise meso -2,4-diaminoglutaric acid a synthetic route has been developed, starting from Garners aldehyde, in which the key step is the hydrogenation of ( Z )-( R )-3- tert -butoxycarbonyl-2,2-dimethyl-4-[2′-(benzamido)-2′-(methoxycarbonyl)ethenyl]-1,3-oxazolidine, followed by oxidation and further hydrolysis.