Parallel synthesis of prostaglandin E1 analogues

The first demonstration of the rapid parallel synthesis of diverse prostaglandin derivatives is reported. Upper (alpha-) side chain diversity was introduced to core 1 via the parallel Suzuki coupling of hydroborated alkenes. Conversion to the enones 3 and 9 was followed by the addition of the lower (omega-) side chains as higher-order cuprates 4. Upper side chains incorporating an N-acylsulfonamide protecting group were further transformed into prostaglandin amide analogues. Cleavage from support with HF/pyridine followed by scavenging provided 26 prostaglandin E-1 analogues in high purity.