Total Synthesis of Fused Natural Products

Natural products are a group of structurally diverse compounds that exhibit various biological activities using their three-dimensional chemical space. Total synthesis studies have been conducted for many years, and synthetic methods and strategies have advanced. However, some compounds, such as complex or large natural products, are still challenging to synthesize. In this article, the author focuses on fused natural products and introduces the total synthesis of aplysiasecosterols and nemorosonols. Aplysiasecosterol A (1) has a unique tricyclic γ-diketone skeleton, and nemorosonol (41) has a tricyclo[4.3.1.03,7]decane skeleton, making it a challenging synthetic target for synthetic organic chemistry. The author’ s strategy for the total synthesis of aplysiasecosterols used the Suzuki-Miyaura coupling reaction for the late-stage bond formation of the C8-C14 bond as a common key reaction. This late-stage convergent synthesis rarely reported in secosteroid synthesis, is adaptable to many 9,11-secosteroids. The author also has established a strategy for constructing a tricyclo[4.3.1.03,7]decane skeleton, which is common to many polycyclic polyprenylated acylphloroglucinols (PPAPs). In this tandem reaction, it is possible to introduce a benzoyl group at the C8 position and adjust the degree of oxidation at the C9 position at the same time. Furthermore, the author achieved the total synthesis of nemorosonol (41) in 12 steps from commercially available cyclopentanone 67 by using the established synthetic strategy.