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.

本文报道了陆生抗炎天然产物linariophyllene A–C的首条半合成路线，以及海洋天然产物rumphellolide H的优化合成路线。在所合成的目标化合物中，研究确定linariophyllene A的正确结构为最初所提出结构的非对映异构体，其二级醇位点的立体中心发生了构型反转。linariophyllene B与rumphellolide H的最初提出的结构均得到了验证。但linariophyllene C的正确结构为最初所提出结构的非对映异构体，其环氧基团的叔碳位点的立体中心发生了构型反转。linariophyllene A–C与rumphellolide H的结构均通过单晶X射线衍射法（single-crystal X-ray diffractometry）得到了确切验证。本研究所得结果为上述天然产物的生物合成起源提出了合理假说，并丰富了现有倍半萜类化合物的多样性。本研究成功获得了足量的linariophyllene A–C与rumphellolide H，可用于进一步拓展其生物活性谱，并作为对照标准品应用于未来陆生与海洋生物化学成分的相关研究中。