A nine-step total synthesis of (-)-platencin.
Within 1 year, platencin, a recently discovered antibiotic, has become a highly competitive synthetic target, due to its promising bioactivity and its unusual complex molecular architecture. Herein, a particularly concise total synthesis of platencin starting from inexpensive perillaldehyde is described. The key features of this approach are (1) a highly diastereoselective Diels-Alder reaction with Rawal's dieneforming the first all-carbon quaternary center, (2) a ring-closing metathesis to generate the strained tricylic skeleton, (3) a hydration/dehydration strategy to efficiently shift the endocyclic alkene to the exoposition, and (4) a 1,4-addition of a hindered ketone enolate to methyl acrylate to create the second all-carbon quaternary center. In view of the brevity (nine linear steps) and the overall yield of 10%, our synthesis compares favorably with all the previous ones.
Tiefenbacher
Konrad
K
Institute of Organic Chemistry, University of Vienna, Wahringerstrasse 38, 1090 Vienna, Austria. konrad.tiefenbacher@uniVie.ac.at
Mulzer
Johann
J
D000627:Aminophenols / Q000138:chemical synthesis* / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003500:Cyclization; D003516:Cycloparaffins / Q000138:chemical synthesis / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D039821:Monoterpenes / Q000138:chemical synthesis / Q000737:chemistry; D011083:Polycyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000627:Aminophenols; D000900:Anti-Bacterial Agents; D003516:Cycloparaffins; D039821:Monoterpenes; D011083:Polycyclic Compounds; C033342:perillaldehyde; C520340:platencin