Maria D. Diaz-de-Villegas

Study of the reaction of imines derived from (R)-glyceraldehyde with Danishefsky's diene

Abstract N-Benzylimines derived from conveniently protected (R)-glyceraldehyde underwent diastereoselective tandem Mannich-Michael reaction with Danishefskys diene in the presence of Lewis acids. The temperature, catalyst and solvent dependence of the product ratio is described. Under zinc iodide-catalysed conditions in acetonitrile at −20°C, double stereodifferentiation using (R)-2,3-di-O-benzylglyceraldehyde (S)-N-α-(methylbenzyl)imine as starting material was successful and the reaction occurred with good yield and complete diastereoselectivity.

Metal complexes of biologically important ligands: Synthesis of amino acidato complexes of PdII containing a C,N-cyclometallated group as an ancillary ligand

Abstract New amino acidato complexes of Pd II of stoichiometry [Pd(CN)(Aa)] (CN C , N -cyclometallated ligand, Aa = N , O -amino acidato ligand) have been obtained by reaction of [Pd(CN)(acac)] (CN N , N -dimethylbenzylamine- C 2 , N (dmba) ( 1 ) or N , N -dimethyl( S - α -phenylethyl)amine- C 2 , N ( S -dmphea) ( 2 )) with glycine, chiral amino acids (alanine, phenylalanine and valine), and amino acid derivatives ( N -acetylglycine and N -acetyl- α , β -dehydroalanine) in MeOH. The compounds are characterized by IR, 1 H and 13 C NMR. The geometry of these complexes has been unambiguously determined by NOE difference experiments and NOESY measurements.

Highly convergent stereoselective synthesis of chiral key intermediates in the synthesis of Palinavir from imines derived from l-glyceraldehyde

Abstract Imines derived from O-protected (S)-glyceraldehyde are valuable intermediates in the synthesis of different kinds of amino acids. We have developed a highly convergent and stereoselective method to obtain (2S,3S)-N-tert-butoxycarbonyl-1-phenyl-3,4-epoxy-2-butylamine and (2S,4R)-N-tert-butoxycarbonyl-4-hydroxypipecolic acid tert-butylamide, which are key intermediates in the synthesis of Palinavir, that consist in the treatment of the appropriate imine with benzylmagnesium bromide and Danishefskys diene, respectively, and subsequent transformation of the obtained adducts into the desired compounds. The reaction of N-benzylimine derived from (S)-2,3-di-O-benzylglyceraldehyde with benzylmagnesium bromide is completely diastereoselective at low temperature. Hetero Diels–Alder reaction of imine derived from (S)-2,3-di-O-benzylglyceraldehyde and (R)-N-α-methylbenzylamine is completely diastereoselective at low temperature in the presence of ZnI2.

Asymmetric Hetero Diels-Alder Reaction of N-Benzylimines Derived from R-Glyceraldehyde: A New Approach to Homochiral Piperidine Building Blocks and its Application to the Synthesis of (2R)-4-Oxopipecolic Acid

Abstract The N-Benzyl imine derived from 2,3-di-O-benzyl-D-glyceraldehyde reacts with Danishefskys diene to afford the corresponding hetero Diels-Alder adduct with a high diastereoselectivity. This compound can be transformed to enantiomerically pure (2R)-4-oxopipecolic acid.

Stereoselective synthesis of α-hydroxy-β-amino acids using D-glyceraldehyde as the homochiral source

Abstract A systematic study of the diastereoselective addition of methyl organometallic compounds to the benzyl imine derived from conveniently protected D -glyceraldehyde in order to develop a new approach to enantiomerically pure α-hydroxy-β-amino acids is reported. Methylmagnesium bromide addition afforded the corresponding adduct, which can be further elaborated to give (2 S ,3 R )-3- amino -2- hydroxybutanoic acid, with complete diastereoselectivity.

Synthesis of new conformationally rigid phenylalanine analogues

Abstract The reactivity of (Z)-2-phenyl-4-benzylidene-5(4H)-oxazolone 1 as dienophile in the Diels-Alder reaction with 1,3-butadiene and 2,3-dimethyl-1,3-butadiene is studied. The adducts obtained starting from the cycloaddition of 1 with both dienes are converted, through simple reactions into the conformationally restricted cyclic amino acids cis-1-amino-2-phenylcyclohexanecarboxylic acid 6 and 1-amino-c-4,c-5-dimethyl-t-2-phenyl-r-1-cyclohexanecarboxylic acid 10 , analogues of phenylalanine.

Reversal of the stereochemical course of the addition of phenylmagnesium bromide to N-benzylimines derived from R-glyceraldehyde depending on the O-protecting group and its application to the synthesis of both enantiomers of phenylglycine

Abstract The N -Benzyl imines derived from 2,3-di- O -benzyl- D -glyceraldehyde and 2,3-di- O -isopropylidene- D -glyceraldehyde reacted with phenylmagnesium bromide to afford fully protected aminodiols with total diastereoselectivity. The stereochemical course of the addition reaction depends on the nature of the O -protecting group. These compounds can be easily transformed to enantiomerically pure ( R ) and ( S ) α -phenylglycine.

A simple synthesis of (−)-(1S,2R)-allocoronamic acid in its enantiomerically pure form

Abstract (−)-(1S,2R)-Allocoronamic acid was synthesized in its enantiomerically pure form by starting from the chiral azlactone derived from 1,2-O-isopropylidene-D-glyceraldehyde in an overall yield of 37 %.

A new approach to the stereoselective synthesis of conveniently protected α-allyl substituted amino acids; chiral key compounds in the synthesis of constrained peptide isostere constituents

Abstract Enantiomerically pure α-allyl-N-Boc-aminoamides were prepared by Curtius rearrangement of α,α-dialkyl chiral 2-cyanoesters obtained by the diastereoselective allylation of chiral 2-cyanoesters according to a modification of our previously described procedure.

New approaches to the asymmetric synthesis of α-methylphenylalanine

Abstract A strategy of highly selective alkylation of chiral 2-cyanoesters followed by the corresponding degradation process allows a divergent asymmetric synthesis of ( R ) and ( S ) -α-methylphenylalanine.