Synthesis and structure of preorganized, C(3)-symmetric trilactam scaffolds with convergently oriented (S)-acetylthiomethyl appendages.
[reaction: see text] Efficient modular synthesis of conformationally preorganized, C(3)-symmetric trilactams is reported. The allyl acetate cyclization substrate was synthesized in five steps from Garner's L-serine-derived aldehyde. After chiral ligand-mediated palladium cyclization, the resulting vinyl hydropyran was transformed into the orthogonally protected amino acids for iterative coupling. The final macrolactamization was accomplished using EDCI/HOBt or HATU/HOAt under high dilution conditions.
Campbell
John E
JE
Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, Wisconsin 53706-1396, USA.
Englund
Erikah E
EE
Burke
Steven D
SD
D002384:Catalysis; D018360:Crystallography, X-Ray; D003500:Cyclization; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000737:chemistry; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000737:chemistry
D006575:Heterocyclic Compounds, 3-Ring; D007769:Lactams; D013438:Sulfhydryl Compounds