Conformation is one of the most fundamental concepts in organic chemistry for chemists to visualize a molecule as a three‐dimensional object in addition to its constitution and configuration. Conformational factors significantly affect the physical properties, chemical reactivities, and biological activities of a molecule. The significance of conformational design has been generally recognized since its successful application in the total synthesis of complex natural products, such as vitamin B12 and erythronolide. Conformational analysis, especially intentional control of conformational preferences by conformational design, could play a critical role in the synthesis of complex organic molecules by guiding the formation of bonds, stereocenters, or rings. This Minireview highlights selected examples of conformational design in natural‐product synthesis, with particular emphasis on the applications and new insights advanced in the last 20 years. The examples discussed herein are divided into three categories by structural features of the substrates: open‐chain type, cyclohexane type, and medium‐ and large‐ring type.

Desaturation of unactivated alkanes remains a challenging yet desirable strategy to make olefins. The Illicium sesquiterpenes usually possess highly oxygenated cage-like architectures, and some of them exhibit prominent neurotrophic effects. Here, we disclose a unique photochemical desaturation strategy for the efficient, highly stereocontrolled total syntheses of five Illicium sesquiterpenes from inexpensive (R)-pulegone, featuring a 13-step gram-scale synthesis of (−)-merrilactone A. The efficiency of the syntheses derives from an expedient construction of a tetracyclic framework via two annulations, a site-specific photoinduced singlestep desaturation in a complex hydrocarbon system, and diverse oxygenation manipulations around the resultant olefin intermediate. This work highlights how late-stage desaturation can dramatically streamline the synthesis of complex terpenes and diverse nonnatural analogues for establishing the structure−activity relationship and elucidating their molecular mechanisms of bioactivity.

An intriguing cage-like polyhemiketal, nesteretal A (1), was isolated from the coral-derived actinomycete Nesterenkonia halobia. Its structure was established by extensive spectroscopic and computational methods. Nesteretal A is a highly oxygenated compound featuring an unprecedented 5/5/5/5 tetracyclic scaffold. A possible biosynthetic pathway of 1 from naturally occurring diacetyl was proposed. Compound 1 showed a weak retinoid X receptor-α (RXRα) transcriptional activation effect.

Conformation is one of the most fundamental concepts in organic chemistry for chemists to visualize a molecule as a three‐dimensional object in addition to its constitution and configuration. Conformational factors significantly affect the physical properties, chemical reactivities, and biological activities of a molecule. The significance of conformational design has been generally recognized since its successful application in the total synthesis of complex natural products, such as vitamin B12 and erythronolide. Conformational analysis, especially intentional control of conformational preferences by conformational design, could play a critical role in the synthesis of complex organic molecules by guiding the formation of bonds, stereocenters, or rings. This Minireview highlights selected examples of conformational design in natural‐product synthesis, with particular emphasis on the applications and new insights advanced in the last 20 years. The examples discussed herein are divided into three categories by structural features of the substrates: open‐chain type, cyclohexane type, and medium‐ and large‐ring type.

In this review, we summarize five instructive total syntheses of marine brominated sesquiterpene aplydactone developed over the past five years.