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

Challenges to the synthesis of bacteriochlorophyll (), the chief pigment for anoxygenic bacterial photosynthesis, include creating the macrocycle along with the -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 by preparation of a hybrid macrocycle (), which contains a -dialkyl group in ring D and a gem-dimethyl group in ring B. Stereochemical definition began with the synthesis of (2,3)-2-ethyl-3-methylpent-4-ynoic acid, a precursor to the -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 -enone (via Nazarov, electrophilic aromatic substitution, and elimination reactions) gave (53% yield) along with a trace of chlorin byproduct (1.4% relative to upon fluorescence assay). exhibited the desired -dialkyl stereochemistry in ring D and was obtained as a 7:1 mixture of (expected) epimers owing to the configuration of the 13-carbomethoxy substituent. The strategy wherein -dialkyl substituents are installed very early and carried through to completion, as validated herein, potentially opens a synthetic path to native photosynthetic pigments.