Total Synthesis of Leukotrienes from Butadiene

Abstract

The total synthesis of leukotrienes has been achieved starting from butadiene by a palladium-catalyzed telomerization at room temperature. A Sharpless catalytic asymmetric epoxidation generated the asymmetric centers with Ͼ94% ee. Simple transformations of the key intermediate 15 produced the leukotrienes LTA 4 methyl ester (4), LTC 4 (1), LTD 4 (2) and

Total synthesis of pro-resolving and tissue-regenerative Protectin sulfido-conjugates

“…The conversion of epoxy ester 4 to 16R,17S-PCTR1 (1) was achieved in two steps as described in Scheme 3. 20,30,31 Reaction of 4 with 3 equiv of glutathione in CH 3 In summary, a concise total synthesis of 16R,17S-PCTR1, 16R,17S-PCTR2 and 16R,17S-PCTR3 has been achieved, 29 making these pro-resolving and tissue-regenerative lipid mediators from docosahexaenoic acid available for further biological and pharmacological testing. The synthesis of other specialized pro-resolving mediators (SPMs) will be reported in due course.…”

In the Arena of Enantioselective Synthesis, Titanium Complexes Wear the Laurel Wreath

“…The acetogenin 45 has been obtained by monoepoxidation of alcohol 1s (Scheme ), followed by dihydroxylation of the isolated olefin and a final cyclization . The oxidation of the alcohol 1t seems to be more interesting since when only the chiral alcohol 5t was used, different leukotrines were prepared . As an illustrative example, lipoxin B 4 ( 46 ) was prepared using 2 equiv of epoxide 5t as the only chiral component.…”

Synthetic Applications of Chiral Unsaturated Epoxy Alcohols Prepared by Sharpless Asymmetric Epoxidation

“…Before the RCM was developed, one of the classical uses of terminal double bonds was as latent acid derivatives. The synthesis of leukotrienes developed by Spur et al [ 25 ] is a prime example: epoxide (3 S )-27 (>94% ee) was converted into the epoxy acetate 30 by acetylation followed by oxidation to acid under Sharpless conditions (RuCl 3 , NaIO 4 ), and esterification with CH 2 N 2 in good overall yield. The acetate was readily hydrolyzed in MeOH using a catalytic amount of K 2 CO 3 plus anhydrous Na 2 SO 4 (no Payne rearrangement or methyl ester cleavage was observed), providing an epoxy alcohol that was oxidized with Py 2 CrO 3 to the aldehyde 31 .…”