title: Synthesis of cyclic peptidosulfonamides by ring-closing metathesis.
abstract: N-Protected beta-aminoethanesulfonyl chlorides (2a-e) were used in the preparation of sulfonamides 4, 8, 11a-c, and 15. Ring-closing metathesis of sulfonamides 4 and 8 did not lead to the expected nine-membered cyclic peptidosulfonamides. In contrast, the allylated peptidosulfonamides 11a-c and 15 turned out to be suitable precursor systems for ring-closing metathesis using second-generation Grubbs catalyst and nine-membered cyclic peptidosulfonamides were obtained in 47-60% yields. The possibility for incorporation of these cyclic peptidosulfonamides into a peptide sequence was illustrated by the incorporation of an amino acid on the "S"- or "N"-terminus leading to 16 and 18-20, respectively. A model of cyclic peptidosulfonamide 16 hints at an extended-like structure.
authors.affiliation: Department of Medicinal Chemistry, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, NL-3508 TB Utrecht, The Netherlands.
authors.forename: Arwin J
authors.initials: AJ
authors.lastname: Brouwer
authors.forename: Rob M J
authors.initials: RM
authors.lastname: Liskamp