Stereoselective synthesis of dipeptide beta-turn mimetics: 7-benzyl and 8-phenyl substituted azabicyclo[4.3.0]nonane amino acid esters.
A stereoselective method has been developed for the synthesis of 7- and 8-substituted dipeptide beta-turn mimetic azabicyclo[4.3.0]nonane amino acid esters. The allyl groups were introduced in high diastereoselectivity, controlled by 3-phenyl or 4-benzyl groups in pyroglutamic acid derivatives 3 or 9, respectively. The precursors, dehydroamino acids 7 and 13 derived from 5 or 11, underwent asymmetric hydrogenations with Burk's DuPHOS Rh(I)-based catalysts to furnish alpha-amino acid derivatives in high stereoselectivity. The resulting amino acids 8 and 14 were converted to the beta-turn mimetics 6,5-bicyclic lactams 1a-d in high yields.
Department of Chemistry, University of Arizona, Tucson, Arizona 85721, USA.
Wei
W
Wang
Jianqing
J
Yang
Jinfa
J
Ying
Chiyi
C
Xiong
Junyi
J
Zhang
Chaozhong
C
Cai
Victor J
VJ
Hruby
D000596:Amino Acids / Q000737:chemistry*; D001372:Aza Compounds / Q000138:chemical synthesis*; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis*; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D004952:Esters; D007202:Indicators and Reagents; D018716:Molecular Mimicry; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis*; D011487:Protein Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000596:Amino Acids; D001372:Aza Compounds; D001643:Bridged Bicyclo Compounds; D004952:Esters; D007202:Indicators and Reagents; D010455:Peptides