Short-Step Total Synthesis of a Cyclopropane-Containing Eicosanoid

Total Synthesis of Halicholactone and Neohalicholactone1

“…From the coupling constants of the terminal cyclopropane protons (H 10a and H 10b ) in the 1 H-NMR spectrum of the major isomer 28 , it was clear that a trans -cyclopropane ring was in place. Excellent agreement with coupling constants of the cyclopropane protons H 7a and H 7b of trans -cyclopropane, and lactone-containing compound 7 were observed. 6a,b …”

“…However, the reaction of 42 with 6.0 equiv of chromium chloride and 2.0 equiv of iodoform in tetrahydrofuran for 16 h at room temperature resulted in only a 11% yield of pure, but unstable, trans -iodo alkene 43 . White has reported the Takai olefination of both ( Z )-4-decenal and (2 S ,4 Z )-2- O -(( tert -butyldiphenylsilyl)oxy)-4-decenal to give the trans -iodo alkenes in 95% yield in each case (after just 3 h at 0 °C) and a more modest 54% yield (after 18 h at 0 °C), respectively. 6a,b Therefore, it appears that oxygen functionality in the substrate severely retards the desired reaction which in our case appeared to permit alternative reaction pathways to become competitive.…”

“…The synthesis of the related natural product 7 was reported in 1993 by White 6a. One of the key steps in the synthesis is the Takai−Kishi coupling of trans -iodo alkene 55 with aldehyde 56 .…”

“…Recently, Gerwick has isolated a series of constanolactones ( 6 ), which are closely related to 7 , from the red marine alga Constantinea simplex off the Oregon coast. 5a,b Gerwick also assigned the absolute stereochemistry of these compounds using a degradative method. During the course of our studies, White reported an elegant synthesis of 7 and constanolactones A ( 6a ) and B ( 6b ) using a route that mimics the proposed biosynthetic pathway and that serves to confirm the indicated absolute stereochemistry of these compounds 5b.…”

Anti-addition of Dimethylsulfoxonium Methylide to Acyclic α,β-Unsaturated Ketones and Its Application in Formal Synthesis of an Eicosanoid

“…22,23 These properties of 16 stimulated several synthetic studies on this compound. 24,21b The structural features of this eicosanoid include a six-membered lactone bearing a cyclopropyl ketone group, whose stereochemistry matches the outcome preparing from the anti-addition of the sulfur ylide to α,β-unsaturated enone in this study, and makes eicosanoid 16 a good target to demonstrate its efficiency (Scheme 3).…”