Total syntheses of natural products containing spirocarbocycles

Abstract

The structures of natural products from a variety of sources contain spirocycles, two rings that share a common atom. The spiro motif is finding increasing inclusion in drug candidates, and as a structural component in several promising classes of chiral ligands used in asymmetric synthesis. Total syntheses of products containing all-carbon spirocycles feature several common methods of ring closure which we examine in this review.

Template‐Directed Synthesis of an Inverted Spiro Architecture

“…The bicyclic spiro geometry can be considered as am olecular 3D equivalent of the Figure-of-eight, typified by connection of two rings to the same tetrahedral core atom.T he inherent three dimensionality combined with rigidity makes spiro bicycles privileged molecular scaffolds. [1] Spirocyclic motifs are generally found in natural products and synthetic drug molecules, [2] as well as hole transport materials [3] and microporous polymers. [4] Thus the synthesis of spirocycles is well established, given its ubiquity across chemical disciplines.…”

Design, Synthesis and Anticancer Evaluation of Spiro [cyclohexane‐1,1′‐indene]‐2,5‐diene Analogues

“…Spirodienones are molecules containing two rings with one shared atom, occurring widely in nature with potential biological activities and are considered important in biosynthetic pathways. The Spiro design is becoming more ubiquitous as outlined in drug discovery, and has been the subject of recent progress on the new synthetic routes to facilitate incorporation of Spiro scaffolds into more pharmaceutically active molecules . Spiro rings of different sizes convey both increased three dimensionality for potential improved activity, and novelty for patenting purposes.…”

“…The Spiro design is becoming more ubiquitous as outlined in drug discovery, and has been the subject of recent progress on the new synthetic routes to facilitate incorporation of Spiro scaffolds into more pharmaceutically active molecules. [1] Spiro rings of different sizes convey both increased three dimensionality for potential improved activity, and novelty for patenting purposes. Due to the structural stringency, these compounds are one of the less focused classes in recent times.…”

Asymmetric synthesis of all-carbon quaternary spirocycles via a catalytic enantioselective allylic alkylation strategy

“…In addition to the application to our own synthetic endeavor, we imagined that this strategy would be amenable to the synthesis of a wide array of all-carbon quaternary spirocyclic compounds, such as acorenone, laurencenone B, and α-chamigrene (Figure 1b). 6 However, this plan hinged on the challenging use of bromomethyl vinyl ketone as an alkylating reagent.…”