Ian Paterson and Natalie Miller from Cambridge University have developed an 18 step synthesis, which incorporates a Jacobsen hetero Diels-Alder reaction as the key step. This produces the marine product in an overall 5.8% yield.
Neopeltolide is a structurally complex marine natural product that potently inhibits the growth of cancer cell lines. It is in very limited supply from its natural sponge source so an efficient synthesis is essential to permit more extensive biological studies.
Whilst this compound has been synthesized before by other research groups, Paterson explains that ‘the beauty of this route is that it uses catalytic asymmetric methods for introducing most of the stereocentres, where the tetrahydropyran ring system is established with excellent control over the stereochemistry by a Jacobsen hetero Diels-Alder reaction.’
Original article: Ian Paterson et al., Chem. Commun., 2008.