Decade-long breakthrough: first total synthesis of bacteriochlorophyll a achieved in lab

After nine years of work, a US team led by Jonathan Lindsey at NC State achieved the first total synthesis of bacteriochlorophyll a, a four-stereocentre macrocycle central to bacterial photosynthesis. The route uses an asymmetric Michael addition to set stereochemistry, a Knoevenagel condensation to join halves, followed by Nazarov cyclisation and electrophilic aromatic substitution to close the macrocycle with the correct configuration. Despite Covid-related supply challenges and the death of a team member in February 2025 slowing progress, the achievement provides access to a range of photosynthetic tetrapyrroles and could be adapted to other native pigments, with plans to streamline the process and improve yields.