Reversal speeds creation of important molecule

Halichondrin B is an inspiring molecule that was discovered in a marine sponge in 1986. Although it was already replicated in the lab several times, Rice University chemists have made it possible to synthesize halichondrin B or its naturally occurring or engineered variations. K.C. is a synthetic chemist. Nicolaou's lab published in the Journal of the American Chemical Society a report on their success in simplifying many of the processes involved in making halichondrin B. The molecular structure of Halichondrin and its potent anti-tumor properties inspired design and synthesis variations (aka analogs). Rice's "reverse approach", to making halichondrin B, led to the fastest route to "highly complex and essential molecule". "This is the quickest of all the reported approaches to the complex natural product," Nicolaou stated. Its significance lies in its potential to further improve and apply it to the rapid synthesis other members of halichondrin's family, as well as novel analogues that could be used as drug candidates. He stated that the Rice lab's technology can be used in principle to produce eribulin. This is a powerful and simple halichondrin B analog clinically used for breast cancer treatment and liposarcoma. The previous and current syntheses for halichondrin B, as well as its analogues, require first bonding carbon atoms and then bonding carbon and oxygen atoms to create cyclicethers. These are key building blocks that will make the molecules. Nicolaou and his coworkers flipped the sequence to create the carbon-oxygen connections. This process is known as the Nicholas etherification. It was then followed by radicalcyclization to form the carbon-carbon bonds and finally to link them to reach the halichondrin A. Nicolaou pointed out that other labs have "flipped” the process to create simpler compounds but had not tried it with halichondrin B. He said that the project was motivated by its importance as a biologically active compound and its complex structure. Their work reduced the number required to create the molecule from 25 steps to 25, using commercially available materials. Nicolaou anticipates that further simplification will not only reduce the steps but also increase the overall yield. This will result in a more cost-effective and efficient chemical process to make this type of compound.


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