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-(N'-tert-butyloxycarbonyl-L~prolyl)-aminoethyl]phenoxy-pentanoic acid (9) has afforded a single cyclopeptide diastereomer,9R-isopropyl-5S,6-trimethylene-8-dearnino-1,2-dihydro-p-phencyclopeptine (4), in 36% yield. From the comparative analysis of the UV, IR, CD, and {sup 1}H NMR spectra of 4 and cyclopeptide 5S,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