Stereoselective synthesis of the gamma-lactam hydrolysate of the thiopeptide cyclothiazomycin.
[reaction: see text] Bohlmann-Rahtz pyridine synthesis of a chiral nonracemic enamine and thiazolylpropynone gives a terminal-protected pyridine-containing gamma-amino acid in high optical purity in a sequential one-pot multicomponent reaction that proceeds with total control of regiochemistry and with minimal racemization. Further elaboration has established the synthesis of the gamma-lactam acidic hydrolysate of the macrocyclic thiopeptide antibiotic cyclothiazomycin, a selective renin inhibitor, in only four steps and 30% overall yield and has confirmed its structure.
Bagley
Mark C
MC
School of Chemistry, Cardiff University, P.O. Box 912, Cardiff, CF10 3TB, UK. bagleymc@cf.ac.uk
Xiong
Xin
X
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002384:Catalysis; D007202:Indicators and Reagents; D007769:Lactams / Q000138:chemical synthesis*; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D007202:Indicators and Reagents; D007769:Lactams; D010455:Peptides; D010456:Peptides, Cyclic; D013844:Thiazoles; C069913:cyclothiazomycin