Peptides with C-terminal aldehydes (PAs) are of interest due to their inhibitory properties toward numerous classes of proteolytic enzymes. In this paper, we describe and compare two novel approaches for the preparation of PAs by solid phase synthesis, one based on the reduction of the Weinreb amide and the other on the reduction of phenyl esters. A study showed that purification of the PAs by chromatography (silica gel or reversed phase) induced a loss of the optical integrity of the C-terminal residue. Both methods were found to be suitable for the synthesis of PAs which were then used for the preparation of reduced-bond-containing peptides on insoluble polymers. The Weinreb amide approach was preferred for the synthesis of PAs due to an uncontrolled over-reduction of phenyl esters in our hands.

The synthesis of chiral 3-substituted quinazoline-2,4-diones was performed starting from N-urethane anthranilamides. This synthetic pathway was applied in solid phase, from commercially available anthranilic acid that was bound to hydroxymethyl polystyrene resin via a carbamate linker. In both cases, cyclisation occurred under basic conditions to afford non-racemized quinazolinediones in high purity.

N-Urethane-protected N-carboxyanhydrides (UNCAs) are very reactive amino acid derivatives. They have been successfully used in peptide synthesis, in both solution and solid phase. We have demonstrated that UNCAs are interesting starting materials for the synthesis of various amino acid derivatives. Chemoselective reduction of UNCAs with sodium borohydride led the corresponding N-protected beta amino alcohols. Reaction of UNCAs with Meldrum's acid, followed by cyclisation, yielded enantiomerically pure tetramic acid derivatives. Diastereoselective reduction of tetramic acid derivatives produced [4S,5S)-N-alkoxycarbonyl-4-hydroxy-5-alkylpyrrolidin-2-ones derived from amino acids, which after hydrolysis yielded statine and statine analogues. Tetramic acid derivatives could also be obtained by reaction of UNCAs with benzyl ethyl malonate in the presence of sodium hydride to yield gamma-N-benzyloxycarbonylamino-beta-oxodicarboxyl esters followed by hydrogenolytic deprotection and decarboxylation. UNCAs also reacted with phosphoranes to produce the ketophosphorane in excellent yields. Subsequent oxidation with oxone or with [bis(acetoxy)-iodo]-benzene produced vicinal tricarbonyl derivatives. These reactions usually proceeded smoothly and with high yields.

The synthesis of chiral N-protected tetramic acid derivatives which are important precursors of β-hydroxy γ-amino acid under mild conditions is described. Reaction of urethane-N-carboxyanhydrides (UNCAs) with Meldrum's acid in the presence of a tertiary amine, followed by subsequent cyclisation produced tetramic acid derivatives. This procedure is applicable to Boc-, Fmoc- and Z- N-carboxyanhydrides.

The complete structural elucidation of the two caffeic acid sugar esters verbascoside and orobanchoside, has been realized by 1H and 13C NMR studies. It has been demonstrated that verbascoside is β-(3′,4′-dihydroxyphenyl)ethyl-O-α-L-rhamnopyranosyl(1→3)-β-D-(4-O-caffeoyl)-glucopyranoside, and orobanchoside is β-hydroxy-β-(3′,4′-dihydroxyphenyl)-ethyl-O-α-L-rhamnopyranosyl(1→2)-β-D-(4-O-caffeoyl)-glucopyranoside.

Appropriate precursors for the synthesis of D-vancosamine and L-evernitrose have been stereospecifically obtained from methyl 4,6-O-benzylidene-2-deoxy-α- and β-D-threo-hexopyranosid-3-ulose.

Various di- and tri-saccharides containing l-rhamnose were synthesized by condensation of 2,3,4-tri-O-acetyl- or 2,3,4-tri-O-benzoyl-α-l-rhamnopyranosyl bromide with an unblocked glycopyranoside. The determination of the anomeric configuration of l-rhamnose saccharides by n.m.r. is difficult because structure has a greater effect on the spectra than does configuration. The α and β configurations and the position of the substitution may be assigned from the chemical shifts of H-5 and CH3. In all the compounds having a β configuration, a shielding of the methyl group and a deshielding of the H-5 proton have been observed as compared to the compounds having an α configuration. The H-5 proton and the methyl group of peracetylated, (1→3)-linked α-l derivatives always resonate at higher fields than the corresponding protons of (1→6)-linked α-l derivatives.

A new glucoside has been isolated from roots of Lithospermum officinale and L. caeruleum. It is not cyanogenetic although containing nitrile group in the aglycone moiety. Its structure has been elucidated by 1H and 13C NMR spectroscopy as 6-O-β-d-glucopyranosyl-1-cyanomethylene-4, 5-dihydroxy-2-cyclohexene.