文摘
We report, for the first time, the synthesis of 8-aza-analogues of PGE2. The SmI2-mediated cross coupling reactions of 纬-lactam-hemiaminal 9, lactam 2-pyridyl sulfide 17, and lactam 2-pyridyl sulfone 18 with activated alkenes/alkyne were first developed, giving the corresponding 纬-lactams in 49鈥?8%, 45鈥?5%, and 75鈥?0%, respectively. The reactions of lactam 2-pyridyl sulfide and 2-pyridyl sulfone proceeded with 鈮?2:1 trans-diastereoselectivities. This represents the first intermolecular coupling reaction of the 纬-lactam N-伪-alkyl radicals of types B, B1, and B2 with activated alkenes. Two radical-based mechanisms were suggested. The asymmetric synthesis of the 11-hydroxylated analogue of the highly selective EP4 receptor agonist PF-04475270 (30), the 11-hydroxylated analogue of ocular hypotensive CP-734432 (31), compounds 35 and 36 have been achieved on the basis of this method.