Cyclopeptide alkaloids. Synthetic, spectroscopic and conformational studies of phencyclopeptine model compounds

Peptide cyclization via the p-nitrophenyl ester of 4-methyl-3(4'..beta..-(((N'-((tert-butyloxy)carbonyl)-L-prolyl)amino)ethyl)phenoxy)pentanoic acid (9) has afforded a single cyclopeptide diastereomer, (5S,9R)-9-isopropyl-5,6-trimethylene-8-deamino-1,2-dihydro-p-phencyclopeptine (4), in 36% yield. From the comparative analysis of the uv,ir, circular dichroism (CD), and /sup 1/H NMR spectra of 4 and cyclopeptide (5S)-5,6-trimethylene-8-deamino-1,2-dihydro-p-phencyclopeptine (3d), of known geometry, the conformational identities of the 14-membered ring systems were ascertained. From these data the assignment of R stereochemistry at C9 for cyclopeptide 4 was deduced. Since the stereochemistry at C9 in the naturally occurring phencyclopeptines is the same, these results suggest a feasible route to the stereoselective total synthesis of the phencyclopeptines.