Investigating the biosynthesis of polyacetylenes synthesis of deuterated linoleic acids & mechanism studies of DMDS addition to 1,4-enynes /

by Zhu, Lizhi.

INVESTIGATING THE BIOSYNTHESIS OF POLYACETYLENES: SYNTHESIS OF DEUTERATED LINOLEIC ACIDS & MECHANISM STUDIES OF DMDS ADDITION TO 1,4-ENYNES By Lizhi Zhu A wide range of polyacetylenic natural products possess antimicrobial, antitumor, and insecticidal properties. The biosyntheses of these natural products are widely distributed among fungi, algae, marine sponges, and higher plants. As details of the biosyntheses of these intriguing compounds remains scarce, it remains important to develop molecular probes and analytical methods to study polyacetylene secondary metabolism. An effective pathway to prepare selectively deuterium-labeled linoleic acids was developed. By this Pd-catalyzed method, deuterium can be easily introduced into the vinyl position providing deuterolinoleates with very high isotopic purity. This method also provides a general route for the construction of 1,4-diene derivatives with different chain lengths and 1,4-diene locations. Linoleic acid derivatives (12-d, 13-d and 16,16,17,17,18,18,18-d7) were synthesized according to this method. A stereoselective synthesis of methyl (14Z)- and (14E)-dehydrocrepenynate was achieved in five to six steps that employed Pd-catalyzed cross-coupling reactions to construct the double bonds between C14 and C15. Compared with earlier methods, the improved syntheses are more convenient (no spinning band distillations or GLC separation of diastereomers were necessary) and higher Z/E ratios were obtained. The overall percent yield for (14E)-isomer was 21% and 29% for the (14Z)-isomer. The reaction between DMDS and 1,4-enynes in the presence of I2 was studied. 2,5-Disubstituted thiophene derivatives were produced as the main products under neutral and acidic conditions. The detailed mechanism of this reaction was studied. Current evidence is consistent with a mechanism that can be described as follows. Initially, electrophilic addition of a sulfenium ion to an alkene yields an episulfonium ion. The subsequent Wagner-Meerwein rearrangement leads to a cationic thietane intermediate through a ring expansion. This four-membered ring is opened by nucleophilic attack of iodide to give a MeSI adduct. Available protons activate the triple bond and promote the subsequent transformations to generate the final thiophene product and release MeI as a side product. The synthetic utility of this method was explored. The optimized reaction provides a mild synthetic route to 2,5-disubstituted thiophene derivatives.