Dienals Derived from Pyridinium Salts and Their Subsequent Application in Natural Product Synthesis

Abstract

Transformation of quaternary pyridinium compounds into functionalized conjugated dienes can be adapted to natural product synthesis with great effect. Most conspicuously, the transformation has been employed in the preparation of polyenic structures. However, in a more convoluted application, polycyclic systems have arisen from elaboration of the diene motif. The goal of the present account is to survey the utility of dienals derived from pyridinium salts as the means to establish molecular architecture featured in natural products.

Recent advances in the chemistry and biology of anti-inflammatory and specialized pro-resolving mediators biosynthesized from n-3 docosapentaenoic acid

“…However, conclusive evidence may only be obtained by preparing 2 by total synthesis and subject the synthetic material to biological systems. 40 The aldehyde 3 was then reacted with thiazolidinone 7 41 in an acetate-aldol reaction to produce intermediate 8 42,43 Desilylation of the two protecting groups using TBAF in THF at 0 °C and subjecting the resulting diol to an atmosphere of hydrogen using the modified Lindlar conditions, 45,46 afforded methyl ester 14 containing the light and heat sensitive E,E,Z-triene in high chemical and stereochemical purity in an acceptable yield. Finally, a basic hydrolysis of the methyl ester 14 afforded multi-milligrams of PD1 n-3 DPA .…”

“…Synthesis of the alpha-end fragment 35.In the end-game of the synthesis, aldehyde 28 and the ylide of Wittig salt 35 were reacted in a Z-selective Wittig reaction, affording the alkyne 38 in 77% yield (Scheme11). After removal of the TBS-group with in situ generated HCl in methanol, the conjugated alkyne in 39 was stereoselectively reduced using the Boland protocol to afford the methyl ester of 13R-HDPA(40). Finally, basic hydrolysis with LiOH gave 13R-HDPA, which matched the authentic natural product.…”

A sequential cycloaddition strategy for the synthesis of Alsmaphorazine B traces a path through a family of Alstonia alkaloids

“…The combination of N (4)-substituted tryptamines with Zincke salts [6,7] proved to be a powerful and direct method for the construction of the key Zincke aldehyde intermediates employed in our past syntheses of polycyclic indole alkaloids. [5] While this method served us well in numerous contexts, we continued to look for complementary methods that would address some of the key synthetic limitations.…”

Synthesis of 5-(S)-HETE, 5-(S)-HEPE and (+)-zooxanthellactone: Three hydroxylated polyunsaturated fatty acid metabolites

“…This E,E-polyene motif is often present in natural products, such as macrolides, polyketides and PUFAs, thus increasing the utilization of these conjugated dines in total synthesis of the aforementioned structures. 227 Treatment of a pyridine sulfur trioxide complex with potassium hydroxide gives rise to a glutaconaldehyde alkoxide. Subsequent interconversion provides the corresponding 5-halopenta-2,4-dienal, which is generally considered exceptionally useful in terms of synthetic application.…”