Triply convergent synthesis of 15-(phenoxymethyl) and 4,5-allenyl prostaglandins. Preparation of an individual isomer of enprostil

Studies towards the total synthesis of an epoxy isoprostane phospholipid, a potent activator of endothelial cells

“…Before attempting the required 3-component coupling 15 we first studied a simpler model, namely the addition of allylcopper 16 to cyclopentenone 23 in the presence of trimethylsilyl chloride (TMSCl) 17 to give the crude silyl enol ether 24. Regeneration of the enolate with methyllithium 18 and trapping with the optically active aldehyde 22 afforded in 90% yield a mixture of four diastereomers 25 (two major and two minor). Elimination of the mesylate 19 and chromatographic separation gave a 1+1 mixture of two diastereomers of the E-enone 26E in 19% yield and predominantly one diastereomer of the Z-enone 26Z in 6% yield.…”

Rh(I)-Catalyzed 1,4-Conjugate Addition of Alkenylboronic Acids to a Cyclopentenone Useful for the Synthesis of Prostaglandins

“…((2,2-Difluorobut-3-yn-1-yl)oxy)benzene (S3). To a round-bottom flask were sequentially added XtalFluor-E 27 (36.0 g, 157.2 mmol, 1.5 equiv), CH 2 Cl 2 (36 mL), Et 3 N•3HF (34.2 mL, 209.8 mmol, 2.0 equiv), and a solution of 1-phenoxybut-3-yn-2-one 28 (16.8 g, 104.9 mmol, 1.0 equiv) in CH 2 Cl 2 (83 mL). The mixture was stirred until (overnight) TLC analysis indicated that the reaction was complete.…”

Synthesis of the Potent Antiglaucoma Agent, Travoprost

“…8 Gooding describes the application of a three-component coupling to unnatural prostaglandins with (E)-CHdCHCH(OH)CH 2 OPh as the ω-side chain, introduced by conjugate addition of a stannane-derived cuprate. 9 Other novel routes to prostaglandin analogues based on alkyne metathesis 10 and nickel-catalysed cyclisation 11 to form the cyclopentane core have appeared recently. From our experience in this area over the past six years we felt that none of these methods were suitable for a scaleable, commercial synthesis of travoprost 2.…”

“…An alternative three-component, two-step variation has also been devised by Johnson . Gooding describes the application of a three-component coupling to unnatural prostaglandins with ( E )-CHCHCH(OH)CH 2 OPh as the ω-side chain, introduced by conjugate addition of a stannane-derived cuprate and nickel-catalysed cyclisation to form the cyclopentane core have appeared recently.…”