From aziridines to carbapenems via a novel β-lactam ring closure : An enantioselective synthesis of (+)-PS-5

✍ Scribed by David Tanner; Peter Somfai

• Publisher: Elsevier Science
• Year: 1988
• Tongue: French
• Weight: 431 KB
• Volume: 44
• Category: Article
• ISSN: 0040-4020
• DOI: 10.1016/s0040-4020(01)85849-x

✦ Synopsis

An enantioselective synthesis of the carbapenem antibiotic (+)-ps-5 is described. The starting point is the chiral Sharpless epoxyalcohol 2 which is transformed stereospecifically to the eziridine 6. Regioeelective ring-ope&ng of 6 by'LiEt Cu followed by RuQ oxidation yields the @-sulfonamide cat-box& acid28 which is cyclia d under-mild conditions and in m&&lent yield to the %tooy,i azetidinone 2. Deprotection at nitrogen, unmasking of the side-chain hydroxyl and oxidation thee furnishes ll, a known advanced intermediate for (t)-PS-5. Due to their unique structure, potent antibacterial activity, and often lov natural abundance, the carbapenee antibiotics (exemplified below by thienamycin. 1 and PS-5, 2) continue to fascinate organic chemists as regards the total synthesis of these important biomoleculesl, two central problems in any totally synthetic approach being control of absolute stereochemistry efficient formation of the S-lactam ring system. and