Synthesis of (-)-halichonic acid and (-)-halichonic acid B

The first syntheses of the amino acids (-)-halichonic acid and (-)-halichonic acid B have been achieved in ten steps starting from commercially available (-)-alpha-bisabolol. The optimized synthetic route includes a new purification method for isolating (-)-7-amino-7,8-dihydrobisabolene in enantiomerically pure form via recrystallization of its benzamide derivative. The key intramolecu-lar aza-Prins reaction forms the characteristic 3-azabicyclo[3.3.1]nonane ring system of halichonic acid along with the lactonized form of halichonic acid B in an 8:1 ratio. Optical rotation measurements confirmed that these synthetic compounds were in fact the enantiomers of the natural products, establishing both the relative and absolute configurations of the halichonic acids.

Automated summary

The synthesis of amino acids (-)-halichonic acid and (-)-halichonic acid B has been successfully achieved in ten steps starting from commercially available (-)-alpha-bisabolol. A new purification method involving recrystallization of the benzamide derivative of (-)-7-amino-7,8-dihydrobisabolene has been developed to obtain enantiomerically pure form. The key intramolecular aza-Prins reaction formed the characteristic ring system of halichonic acid and halichonic acid B in a specific ratio.