Ralph F. Hirschmann award address 2009: Merger of organic chemistry with peptide diversity.

A huge unleashed potential lies hidden in the large and diverse pool of encoded and particularly nonencoded chiral alpha-, beta-, and gamma-amino acids available today. Although these have been extensively exploited in peptide science, the community of organic chemistry has only used this source of diversity in a quite focused and targeted manner. The properties and behavior of peptides as functional molecules in biology are well documented and based on the ability of peptides to adapt a range of discrete conformers at a minimal entropic penalty and therefore ideally fitting their endogenous targets.

Nonradical zinc-Barbier reaction for diastereoselective synthesis of vicinal amino alcohols.

A new protocol for the synthesis of vicinal amino alcohols is described. The method employs a Barbier-type reaction between an imine and 3-benzoyloxyallyl bromide in the presence of zinc metal. The addition products are debenzoylated to afford amino alcohols in good yields and with diastereomeric ratios greater than 85:15 in favor of the anti isomer.

A concise synthetic route to the conduritols from pentoses.

A short synthetic strategy for preparation of the conduritols is described. The key step employs a zinc-mediated fragmentation of protected methyl 5-deoxy-5-iodo-d-pentofuranosides followed by an allylation of the intermediate aldehyde in the same pot. The allylation is performed with 3-bromopropenyl benzoate and occurs with good diastereoselectivity.

Combinatorial libraries - from solution to 2D microarrays.

Enzymatic modifications of split and mix libraries were followed by "pulling down" onto a 2-dimensional DNA microarray, via PNA tagging; this allowed complete library interrogation of all members of the split and mix library.

2'-Spiro ribo- and arabinonucleosides: synthesis, molecular modelling and incorporation into oligodeoxynucleotides.

We have synthesized four conformationally restricted bicyclic 2'-spiro nucleosides via 2'-C-allyl nucleosides as key intermediates. The ribo-configured 2'-spironucleosides 9b and 14b were obtained by a convergent strategy starting from 2-ketofuranose 1 whereas the arabino-configured 2'-spironucleosides 21 and 27 were obtained by a linear strategy with a 2'-ketouridine derivative as starting material. The furanose ring of 9b/14b adopts N-type conformations whereas the furanose ring of 21/27 exists as an N<==>S equilibrium.