Semisynthesis of Linariophyllenes A–C and Rumphellolide H, Structure Revisions and Proposed Biosynthesis Pathways

The
first semisynthetic routes toward terrestrial anti-inflammatory
natural products linariophyllene A–C and the refined route
toward marine natural product rumphellolide H are presented. Among
the synthesized target compounds, the correct structure of linariophyllene
A was determined to be the diastereomer of the originally proposed
structure with an inverted stereocenter at the secondary alcohol.
The proposed structures of linariophyllene B and rumphellolide H were
confirmed. However, the correct structure of linariophyllene C was
found to be the diastereomer of the originally proposed structure
with an inverted stereocenter at the tertiary carbon of the epoxide
moiety. The structures of linariophyllenes A–C and rumphellolide
H were unequivocally confirmed by single-crystal X-ray diffractometry.
The obtained results enabled the proposal of the biosynthetic origins
of the aforementioned natural products and bolstered the diversity
of available sesquiterpenoids. Linariophyllenes A–C and rumphellolide
H were obtained in sufficient amounts to further expand their bioactivity
profile and utility as reference standards in future studies of chemical
constituents of terrestrial and marine organisms.