Synthesis of Triamino Acid Building Blocks with Different Lipophilicities

<div><p>To obtain different amino acids with varying lipophilicity and that can carry up to three positive charges we have developed a number of new triamino acid building blocks. One set of building blocks was achieved by aminoethyl extension, <i>via</i> reductive amination, of the side chain of ortnithine, diaminopropanoic and diaminobutanoic acid. A second set of triamino acids with the aminoethyl extension having hydrocarbon side chains was synthesized from diaminobutanoic acid. The aldehydes needed for the extension by reductive amination were synthesized from the corresponding Fmoc-L-2-amino fatty acids in two steps. Reductive amination of these compounds with Boc-L-Dab-OH gave the C4-C8 alkyl-branched triamino acids. All triamino acids were subsequently Boc-protected at the formed secondary amine to make the monomers appropriate for the N-terminus position when performing Fmoc-based solid-phase peptide synthesis.</p></div

Synthesis of triamino acid building blocks with varied lipophilic tails.

<p>(i) NaBH₃CN, 1% AcOH in methanol, rt, 18 h (ii) (Boc)₂O, water:dioxane (v/v, 1:1), 10% aq. soln. of Na₂CO₃, rt, 18 h.</p

Schematic structures of the triamino acid building blocks.

<p>(P₁-P₃ = protecting groups).</p

Synthesis of alkyl branched amino aldehydes.

<p>(i) EtSH, DCC, DMAP, dichloromethane at rt, 2 h (ii) Triethylsilane, 10% Pd/C, acetone at rt, 2 h.</p

A highly efficient and facile one pot synthesis of novel 1-glycopyranosyl-4-biaryl butenone derivatives

A facile and efficient methodology, comprised of a domino reaction, a Suzuki-Miyaura coupling reaction followed by an aldol condensation has been developed to synthesize novel 1-glycopyranosyl-4-biaryl butenone derivatives in a one-pot fashion. The reaction of C-glycosides 1-C-(β-D-glucosyl)propan-2-one, 1-C-(β-D-mannosyl)propan-2-one, 1-C-(β-D-galactosyl)propan-2-one, 1-C-(β-D-lactosyl)propan-2-one with 5-bromothiophene-2-carboxaldehyde or 4-bromobenzaldehyde and different boronic acids in the presence of Pd(II)-catalyst and a base in methanol at room temperature produced various chalcone type biphenyl C-glycosides in 75–85% yields. </p

Biocatalytic route to <i>C</i>-4′-spiro-oxetano-xylofuranosyl pyrimidine nucleosides

<p>A facile access to <i>C</i>-4′-spiro-oxetano-xylofuranosyl nucleosides has been demonstrated for the first time through Lipozyme^® TL IM-mediated regioselective acetylation of one of the primary hydroxyl group over the other primary and secondary hydroxyl groups in 3′-<i>O</i>-benzyl-4′-<i>C</i>-hydroxymethyl-<i>β</i>-D-xylofuranosyl nucleosides. Attempts to optimize a convergent route for these spironucleosides via selective manipulation of hydroxyl groups in 3-<i>O</i>-benzyl-4-<i>C</i>-hydroxymethyl-1,2-<i>O</i>-isopropylidene-α-D-xylofuranose were unsuccessful. Nevertheless; the present linear biocatalytic route efficiently afforded the <i>C</i>-4′-spiro-oxetanoxylofuranosyl nucleosides T and U in 47 and 38% overall yields, respectively, starting from corresponding furanose diol.</p

Synthesis of novel 3′-azido-3′-deoxy-α-L-<i>ribo</i> configured nucleosides: A comparative study between chemical and chemo-enzymatic methodologies

<p></p> <p>Syntheses of novel 3′-azido-3′-deoxy-2′-<i>O</i>,4′-<i>C</i>-methylene-<i>α-</i>L-<i>ribo</i>furanosyl nucleosides have been carried out from 3′-azido-3′-deoxy-4′-<i>C</i>-hydroxymethyl-β-D-<i>xylo</i>furanosyl nucleosides following both chemical and chemo-enzymatic methodologies. The precursor nucleoside in turn was synthesized from a common glycosyl donor 4-<i>C</i>-acetoxymethyl-1,2,5-tri-<i>O</i>-acetyl-3-azido-3-deoxy-<i>α,β</i>-D-<i>xylo</i>furanose, which was obtained by the acetolysis of 4-<i>C</i>-acetoxymethyl-5-<i>O</i>-acetyl-3-azido-3-deoxy-1,2-<i>O</i>-isopropylidene-α-D-<i>xylo</i>furanose in 96% yield. It has been observed that a chemo-enzymatic pathway for the synthesis of targeted nucleosides is much more efficient than a chemical pathway, leading to the improvement in yield for the synthesis of 3′-azido-3′-deoxy-<i>α-</i>L-<i>ribo</i>furanosyl thymine and uracil from 49 to 89% and 55 to 93%, respectively.</p