Total synthesis of (-)-tetrazomine. Determination of the stereochemistry of tetrazomine and the synthesis and biological activity of tetrazomine analogues.
The first total synthesis of the potent antitumor antibiotic (-)-tetrazomine has been accomplished. A new method for the formation of the allylic amine precursor to an azomethine ylide has been developed and exploited in an efficient [1,3]-dipolar cycloaddition to afford the key tetracyclic intermediate used in the synthesis of (-)-tetrazomine. Several analogues of tetrazomine have been synthesized and tested for antimicrobial and biochemical activity.
Scott
Jack D
JD
Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA.
Williams
Robert M
RM
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001483:Base Sequence; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D010880:Piperidines; C069637:tetrazomine; D004247:DNA