Rapid Synthesis of anti-1,3-Diamino-4-phenylbutan-2-ol Building Blocks via a Three-Component Oxyhomologation and a Two-Component Reducing System.

N-substituted derivatives of anti-(2R,3S)-1,3-diamino-4-phenylbutan-2-ol are important building blocks for the synthesis of therapeutically important molecules. We describe a simple protocol that allows transformation of N,N-dibenzyl-L-phenylalaninal into such compounds in only two steps. The first step is a fully stereoselective three-component MAC (Masked Acyl Cyanide) oxyhomologation reaction implicating different amines to give a panel of ten N,N-dibenzyl-O-tert-butyldimethylsilyl-protected anti-(2S,3S)-allophenylnorstatin amides.

High Diastereoselectivity in a Tandem Oxyhomologation-Coupling Protocol for the Preparation of Amides and Peptides Incorporating α-Hydroxy β-Amino Acids.

The one-pot MAC (Masked Acyl Cyanide) reaction is used to perform the tandem oxyhomologation reaction of -dibenzyl-l-phenylalaninal and coupling with nitrogen nucleophiles to provide a wide selection of amide and peptide derivatives of (2,3)-allophenylnorstatin in generally good yields and with high selectivity, often with dr >98:2. The procedure works equally well with other selected -dibenzyl α-amino aldehydes, and is used to achieve a very short synthesis of (23)-epibestatin.

A case study of the MAC (masked acyl cyanide) oxyhomologation of ,-dibenzyl-L-phenylalaninal with diastereoselectivity: preparation of (2,3)-allophenylnorstatin esters.

The three-component reaction between a protected α-amino aldehyde, an alcohol and an α-silyloxymalononitrile provides an expedient access to protected α-hydroxy-β-amino acid derivatives. The prototypical process, performed on -Cbz-phenylalaninal, is known to proceed with diastereoselectivity. The present study demonstrates that the diastereoselectivity of the reaction can be inverted, using the rationale of a Felkin-Anh interaction model.

Reversal of Diastereoselectivity in a Masked Acyl Cyanide (MAC) Reaction: Synthesis of Protected erythro-β-Hydroxyaspartate Derivatives.

Using Garner's aldehyde as a substrate, one-pot MAC hydroxyhomologation reactions proceeded in good yields and with anti selectivity for the first time (dr up to 9:1). The products were used to prepare a panel of protected derivatives of erythro-β-hydroxyaspartic acid and erythro-β-hydroxyasparagine as single enantiomers in a few steps.

Studies on cyclization reactions of 3-amino-2,4-dihydroxybutanoic acid derivatives.

A number of cyclic derivatives of 3-amino-2,4-dihydroxybutanoic acid are known in the literature but they are often prepared from other cyclic precursors. This study showed that the title compound too may serve as a convenient substrate for cyclization reactions. Using orthogonally-protected linear derivatives, regioselective cyclizations were performed, leading to original and highly-functionalized γ-lactones, oxazolidinones, oxazolines and aziridines.

29Si-1H IMPACT HMBC: a suitable tool for analyzing silylated derivatives.

A modified version of the IMPACT heteronuclear multiple bond correlation (HMBC) has allowed the characterization of an organosilane and a tetrasilylated yttrium complex. With the help of this sequence, an average gain in sensitivity close to 2 has been obtained compared with the standard HMBC experiment for disilanes as well as for yttrium complexes containing silylated ligands. This modified version of this long-range correlation experiment opens the way for following kinetics in the range of a fraction of a minute and to study by NMR low concentrated samples and low abundant nuclei.