The synthesis of methyl N-(1-aza-6-oxaspiro[2.5]oct-1-en-2-yl)-L-prolinate
(1e) has been performed by consecutive treatment of methyl N-[(tetrahydro-2
H-pyran-4-yl)thiocarbonyl]-L-prolinate (5) with COCl2, 1,4-diazabicyclo[2.2
.2]octane (DABCO), and NaN3 (Scheme 1). As the first example of a novel cla
ss of dipeptide synthons, le has been shown to undergo the expected reactio
ns with carboxylic acids and thioacids (Scheme 2). The successful preparati
on of the nonapeptide 16, which is an analogue of the C-terminal nonapeptid
e of the antibiotic Trichovirin 1 1B, proved that 1e can be used in peptide
synthesis as a dipeptide building block (Scheme 3). The structure of 7 has
been established by X-ray crystal-structure analysis (Figs. 1 and 2).