Access to isocarbacyclin derivatives via substrate-controlled enolate formation: total synthesis of 15-deoxy-16-(m-tolyl)- 17,18,19,20-tetranorisocarbacyclin.
[reaction: see text] We describe a convergent and flexible synthesis of 15-deoxy-16-(m-tolyl)-17,18,19,20-tetranorisocarbacyclin (15-deoxy-TIC), a simple isocarbacyclin derivative. The synthesis takes advantage of two key step reactions: a regioselective deprotonation of the described ketone under substrate control which is then trapped, as the enol triflate, to generate the C6-C9alpha endocyclic double bond, followed by an sp2-sp3 Pd-catalyzed cross-coupling reaction (C5-C6) with a suitable primary alkyl Grignard reagent. Introduction of the C13-C14 (E)-double bond in the omega-side chain is performed by the Julia-Kocieñski olefination.
Sheddan
Neil A
NA
Institut für Organische Chemie, Währingerstrasse 38, A-1090 Wien, Austria.
Mulzer
Johann
J
D002384:Catalysis; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D013237:Stereoisomerism
C401841:15-deoxy-16-m-tolyl-17,18,19,20-tetranorisocarbacyclin; D010165:Palladium; D011464:Epoprostenol