Evaluating coupling procedures for synthesis of lna-Peptide conjugates.

As initial studies of block coupling of peptides with C-terminal glycines, we have evaluated of coupling of glycine building blocks under various conditions to a preassembled solid support bound LNA-fragment. Potentially competing side reaction have been studied and we have worked out a procedure for trifluoroacetyl protection of peptides.

Highly diastereoselective hydrogenations leading to beta-hydroxy delta-lactones in hydroxy-protected form. A modified view of delta-lactone conformations.

Enol MEM ethers 4 and 15 and the corresponding enol acetates were hydrogenated over Pd/C with very high (>99%) diastereoselectivity to saturated delta-lactones. A stereochemical generalization can be formulated thus: trans-5,6-disubstituted 1-oxa-3-cyclohexen-2-ones (e.g.