Practical synthesis of blepharismone, a mating inducing pheromone of Blepharisma japonicum

Both enantiomers of blepharismone, a mating inducing pheromone produced by type II cells of Blepharisma japonicum, were synthesized via the Stille cross-coupling reaction of [4-(tert-butyl-dimethyl-silanyloxy)-2-trimethylstannanyl-phenyl]-carbamic acid tert-butyl ester with an acid chloride derived from (S)- and (R)-malic acid as a key reaction. The mating inducing activity of synthetic (S)-blepharismone was as effective as that of the natural one. The enantiomer (R)-blepharismone showed no mating inducing activity.

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(S)-{4-(tert-Butyl-dimethyl-silanyloxy)-2-[2-(2,2-dimethyl-5-oxo-[1,3]dioxolan-4-yl)-acetyl]-phenyl}-carbamic acid tert-butyl ester[α]D28=+4.61 (c 3.93, CH3OH)Source of chirality: (S)-malic acidAbsolute configuration: (S)

(S)-{2-[2-(2,2-Dimethyl-5-oxo-[1,3]dioxolan-4-yl)-acetyl]-4-hydroxy-phenyl}-carbamic acid tert-butyl ester[α]D25=+6.55 (c 3.97, CH3OH)Source of chirality: (S)-malic acidAbsolute configuration: (S)

(S)-4-(2-Formylamino-5-methoxy-phenyl)-2-hydroxy-4-oxo-butyric acid methyl ester[α]D25=+3.52 (c 0.4, CH3OH)Source of chirality: (S)-malic acidAbsolute configuration: (S)

(S)-Blepharismone[α]D27=-94.5 (c 1.07, DMSO)Source of chirality: (S)-malic acidAbsolute configuration: (S)