A stereoselective synthesis for the (5Z,9Z)-14-methyl-5,9-pentadecadienoic acid and its monounsaturated analog (Z)-14-methyl-9-pentadecenoic acid

Methyl-Branched Fatty Acids, Inhibitors of Enoyl-ACP Reductase with Antibacterial Activity from Streptomyces sp. A251

“…The double-bond position of compound 2 was determined in a similar way to be C-9. Thus, the chemical structures of compounds 1 and 2 were identified as 14-methyl-9(Z)-pentadecenoic acid [3] and 15methyl-9(Z)-hexadecenoic acid [4], respectively, as follows: 14 FabI, FabG, and FabK Assays S. aureus FabI and FabG and S. pneumoniae FabK assays were performed as described previously [20,25,26]. Assays were carried out in half-area, 96-well microtiter plates.…”

“…A251. The inhibitors were identified as 14-methyl-9(Z)-pentadecenoic acid (MPDA) [3] and 15-methyl-9(Z)hexadecenoic acid (MHDA) [4] by chemical modification and MS and NMR spectral data (Fig. 1).…”

An improved synthesis for the (Z)-14-methyl-9-pentadecenoic acid and its topoisomerase I inhibitory activity

“…The first total synthesis for 1 was recently reported by us. 10 In this first generation synthesis the synthetic approach involved the initial coupling of (trimethylsilyl)acetylene to 4-methyl-1-bromopentane resulting in a volatile iso-alkyne followed, after removal of the silyl protecting group, by a second acetylide coupling to a longer-chain bromoalkane bearing a functional group (e.g., the protected alcohol 3 in Scheme 1) that could later be transformed into the carboxylic acid. The advantage of this strategy is that, after Lindlar hydrogenation of the resulting internal alkyne, a 100% Z stereoselectivity for the C-9 double bond was obtained.…”

“…The advantage of this strategy is that, after Lindlar hydrogenation of the resulting internal alkyne, a 100% Z stereoselectivity for the C-9 double bond was obtained. 10 However, still a synthetic limitation to this approach was that the 6-methyl-1-heptyne is quite volatile, and the yields for the second alkyne-bromide coupling reaction were rather low (33% yields). 10 Therefore, we envisaged that by reversing the coupling order, i.e., initial coupling of (trimethylsilyl)acetylene to 3 (Scheme 1) followed by a second acetylide coupling to 4-methyl-1-bromopentane would result in higher overall yields.…”

“…10 However, still a synthetic limitation to this approach was that the 6-methyl-1-heptyne is quite volatile, and the yields for the second alkyne-bromide coupling reaction were rather low (33% yields). 10 Therefore, we envisaged that by reversing the coupling order, i.e., initial coupling of (trimethylsilyl)acetylene to 3 (Scheme 1) followed by a second acetylide coupling to 4-methyl-1-bromopentane would result in higher overall yields. This is the synthetic strategy we employed herein for the second generation synthesis of the required (Z)-14-methyl-9-pentadecenoic acid (1) (Scheme 1).…”