Bone collagen cross-links: A convergent synthesis of (+)-deoxypyrrololine

A convergent total synthesis of (+)-deoxypyrrololine (Dpl, 4), a putative c ross-link of bone collagen, is described starting from a commercially avail able L-glutamic acid derivative, (4S)-5-(tert-butoxy)47[(tert-butoxycarbony l)amino]-5-oxopentanic acid (16). Condensation of aldehyde (S)-(-)-17 with nitro compound (S)-(-)-27, both of which were prepared from a common precur sor (S)-16, gave the alpha -hydroxynitro compound 28, which upon; acetylati on afforded alpha -acetoxynitro compound,14 in good yield. Subsequent conde nsation and cyclization of a-acetoxynitro compound 14 with benzyl isocyanoa cetate (15) in the presence of DBU in THF gave the key pyrrole intermediate (S,S)-(-)-12 in 57% yield. N-Alkylation of pyrrole (S,S)-(-)-12 with iodid e (S)-(-)-13 using t-BuOK in THF afforded the 2-benzyloxycarbonyl-1,3,4-sub stituted pyrrole derivative (-)-29 in 42% yield. Removal of the protective groups in (-)-29 followed by hydrogenolysis and decarboxylation afforded th e cross-link (+)-Dpl (4) in good overall yield. The synthesis of an analogu e (S)-(+)-24 ana formation of a novel tetrahydroindole derivative(-)-31 are also described.