Synthesis of Cyclohexane-Angularly-Fused Triquinanes

Abstract

Cyclohexane-angularly-fused triquinanes, 6-5-5-5 tetra­cycles, have attracted the attention of synthetic chemists due to their highly congested core structures and multiple quaternary carbon centers. This review focuses on the six completed total synthesis of naturally occurring cyclohexane-angularly-fused triquinanes in addition to seven notable methodologies that have been developed for the synthesis of these structures.1 Introduction2 6-5-5-5 Tetracycles Containing a Linear Triquinane2.1 Total Synthesis of Cyclopiane Diterpenes2.2 Synthetic Approach toward Aberrarane Diterpenes2.3 Intermediates in the Total Synthesis of Magellanine-Type Alkaloids3 6-5-5-5 Tetracycles Containing an Angular Triquinane3.1 Total Synthesis of Waihoensene3.2 Miscellaneous Approaches4 Conclusion

Total Synthesis of (+)-Aberrarone

“…26 It is noteworthy that the C3 methyl group of 23 epimerized easily under acid condition and yielded the undesired 24. Finally, Riley oxidation of 23 with SeO 2 in 1,4-dioxane furnished (+)-aberrarone (1). All analytical data ( 1 H NMR, 13 C NMR, HRMS, IR, and[α] 25.0 D ) of the synthesized 1 matched with that reported for the natural product.…”

“…Cyclohexane-angularly-fused triquinane natural products can be categorized into two classes on the basis of the structure of triquinanes (Scheme ): linear triquinanes A , such as aberrarone ( 1 ) and conidiogenone B ( 2 ), and angular triquinanes B , such as waihoensene ( 3 ) . These natural products have recently attracted widespread attention of the synthetic community because of their complex structures and promising biological activities, and many novel methodologies have been developed for the synthesis of these tetracyclic scaffolds. − However, the triquinane units are constructed step by step, and a one-step method for the formation of triquinane has not yet been reported.…”

Enantioselective Total Synthesis of (+)-Aberrarone

“…Linear triquinanes with angular fused cyclohexanes are salient features of more than 20 natural products from diverse natural sources. − In 2009 Rodriguez and co-workers isolated (+)-aberrarone ( 1 ) from the gorgonian coral Pseudopterogorgia elisabethae , which has been a rich source of natural products since the 1980s. , Extracts of the coral exhibit anti-inflammatory effects and are present in various skin care products . (+)-Aberrarone bears a 5–5–5–6 ring system, four ketones, three quaternary carbons, and seven stereogenic centers, six of which are contiguous, rendering it an intriguing target for synthesis (Scheme ).…”