First total synthesis of macrocycle with four stereocentres at the heart of bacterial photosynthesis

Good news! But the abstract of this research is loaded with technical terms.

"After nine years of effort, chemists in the US have completed the first total synthesis of bacteriochlorophyll a, a molecule they describe as ‘one of the most challenging photosynthetic tetrapyrroles to synthesise’. ... approach opens the door to making a wide range of photosynthetic tetrapyrroles and exploring their function ‘in a way that’s not been possible previously’. ...

Photosynthetic tetrapyrroles are organic compounds made up of four pyrrole rings. Common examples are bacteriochlorophyll a and chlorophyll a, the main pigments in anoxygenic and oxygenic photosynthesis, respectively. ..."

"Researchers ... have successfully synthesized bacteriochlorophyll a, a photosynthetic pigment found in bacteria which absorbs infrared light. The work represents the first chemical synthesis of this molecule and could give scientists deeper insights into photosynthetic function and photosynthetic energy. ...

“What we did was synthesize both halves of the macrocycle [made up of rings A,B,C, and D], then use constituents of ring E as the joining site for bringing the two halves together,” ... “When the halves are attached to an atom that will eventually become ring E, a cascade reaction triggers and the molecule self-assembles in the last step.”"

From the abstract:

"Photosynthetic tetrapyrroles absorb light to power the biosphere but have largely been neglected as targets of chemical synthesis.

Bacteriochlorophyll a – a key macrocycle in the bacterial photosynthetic reaction center – contains four stereocenters at the rim of the bacteriochlorin chromophore due to the trans-dialkyl group in each pyrroline ring (B, D), and an epimerizable β-ketoester embedded in the isocyclic ring (E).

Here, each pair of stereodefined vicinal substituents was introduced as a chiral 4-nitroalkanal building block, which was converted to an alkynone for subsequent coupling with an iodopyrrole (A, C), affording the AD and BC dihydrodipyrrins. The dihydrodipyrrins were equipped with reactive groups (1-formyl, AD-half; 1-(1,1-dimethoxymethyl) and 8-(3-methoxy-1,3-dioxopropyl, BC-half) suited for directed macrocycle formation.

Knoevenagel condensation of AD and BC halves afforded a propenone, the nexus for constructing ring E concomitantly with the macrocycle in the subsequent one-flask, double-ring closure (Nazarov cyclization, electrophilic aromatic substitution, elimination of methanol).

The aromatic bacteriopheophorbide was obtained as the 2-trimethylsilylethyl propanoate, which upon acidolysis and esterification with phytol yielded bacteriopheophytin a; subsequent magnesiation gave bacteriochlorophyll a.

The modularity of the synthesis, straightforward construction of asymmetric building blocks, and convergent joining of AD and BC halves suggest that the present route may provide an entrée into diverse photosynthetic macrocycles."

First total synthesis of macrocycle with four stereocentres at the heart of bacterial photosynthesis | Research | Chemistry World

Researchers Synthesize Photosynthetic Molecule Found in Bacteria (original news release)

Synthesis of bacteriochlorophyll a (open access)

Bacteriochlorophyll a is the most common photosynthetic pigment in anoxygenic photosynthetic bacteria, and plays significant roles in light-harvesting, energy-migrating and electron-transporting reactions