Asymmetric Synthesis of a Bacteriochlorophyll Model Compound Containing trans -Dialkyl Substituents in Ring D.

Challenges to the de novo synthesis of bacteriochlorophyll a ( BChl a ), the chief pigment for anoxygenic bacterial photosynthesis, include creating the macrocycle along with the trans -dialkyl substituents in both pyrroline rings (B and D). A known route to a model bacteriochlorophyll with a gem-dimethyl group in each pyrroline ring has been probed for utility in the synthesis of BChl a by preparation of a hybrid macrocycle ( BC-1 ), which contains a trans -dialkyl group in ring D and a gem-dimethyl group in ring B. Stereochemical definition began with the synthesis of (2 S ,3 S )-2-ethyl-3-methylpent-4-ynoic acid, a precursor to the trans -dialkyl-substituted AD dihydrodipyrrin. Knoevenagel condensation of the latter and a gem-dimethyl, β-ketoester-substituted BC dihydrodipyrrin afforded the enone (E, 70%; Z, 3%); subsequent double-ring cyclization of the E -enone (via Nazarov, electrophilic aromatic substitution, and elimination reactions) gave BC-1 (53% yield) along with a trace of chlorin byproduct (1.4% relative to BC-1 upon fluorescence assay). BC-1 exhibited the desired trans -dialkyl stereochemistry in ring D and was obtained as a 7:1 mixture of (expected) epimers owing to the configuration of the 13 ² -carbomethoxy substituent. The strategy wherein trans -dialkyl substituents are installed very early and carried through to completion, as validated herein, potentially opens a synthetic path to native photosynthetic pigments.