Stereoselective Synthesis of Uridine-Derived Nucleosyl Amino Acids

Novel hybrid structures of 5′-deoxyuridine and
glycine were
conceived and synthesized. Such nucleosyl amino acids (NAAs) represent
simplified analogues of the core structure of muraymycin nucleoside
antibiotics, making them useful synthetic building blocks for structure–activity
relationship (SAR) studies. The key step of the developed synthetic
route was the efficient and highly diastereoselective asymmetric hydrogenation
of didehydro amino acid precursors toward protected NAAs. It was anticipated
that the synthesis of unprotected muraymycin derivatives via this
route would require a suitable intermediate protecting group at the
N-3 of the uracil base. After initial attempts using PMB- and BOM-N-3
protection, both of which resulted in problematic deprotection steps,
an N-3 protecting group-free route was envisaged. In spite of the
pronounced acidity of the uracil-3-NH, this route worked equally efficient
and with identical stereoselectivities as the initial strategies involving
N-3 protection. The obtained NAA building blocks were employed for
the synthesis of truncated 5′-deoxymuraymycin analogues.