What is the meaning of the synthesis of diastereomer of natural product?

Question

I've heard that synthesis of diastereomer of natural product is more important than synthesis of natural product. But I still wonder why it is. For pharmaceutical issues or others, I think total synthesis of natural product is more critical than synthesis of diastereomer of natural product. If absolute configuration and its structure was determined by extensive research, what is the meaning of the synthesis of diastereomer of natural product?

Answer 1

I’m not sure I totally understand your question, but let me try to explain what is generally an important point around natural or pharmaceutical compounds containing one or more chiral centers.

An important principal is that the pharmacology (efficacy and safety) of any molecule to be developed as a medicine should be fully characterized. If you develop a molecule with 2 chiral centers for example, this means there are 4 isomers. Typically, the absolute configuration of a molecule is critical, because it needs to bind to a specific binding site or receptor. Going back to the natural product, the pharmacologist needs to understand which enantiomer is responsible for the pharmacological activity of the natural product and isolate or synthesize the relevant isomer. It’s also possible that one of the other isomers could cause an adverse or side effect.

The FDA is now very strict on allowing the pure and active enantiomer to be approved for therapeutic use.