Total Synthesis of (±)-Waihoensene
Recently, waihoensene, a tetracyclic natural product with congested structural features was recognized as one of the ultimate challenges for total synthesis by the synthetic organic chemistry community.
KAIST researchers in the Department of Chemistry led by Professor Hee-Yoon Lee, reported the first total synthesis of waihoensene, a tetracyclic diterpene natural product.
The total synthesis was accomplished by a creative method involving a trimethylenemethane diradical species (TMM diyl) and a tandem cycloaddition that was, in fact, previously developed by the Lee group.
In terpene type natural products, isolated quaternary stereogenic centers (see Figure) and sequences of contiguous tetrasubstituted carbon atoms belong to a class of the most complex structural elements.
The steric congestion surrounding these stereogenic carbon centers and a current limited availability of suitable carbon-carbon bond-forming reactions makes the construction of contiguous quaternary carbon centers one of the most challenging tasks for synthetic chemists.
The fact that waihoensene has four quaternary carbon centers next to each other (sequential, see below) held in a tetracyclic structure!
This evokes a lot of attention from .chemists since the isolation of this species in 1997.
Although there were several earnest attempts to synthesize waihoensene, due to the molecule’s structural complexity, it has not been accomplished until now.
Waihoensene was selected as one of the most outstanding targets for the 21st century, according to a comprehensive review that described contemporary developments and synthetic strategies towards, among other targets, multiple quaternary carbon centers.
Thus, for the first time, researchers led by Professor Hee-Yoon Lee in the Department of Chemistry at KAIST reported the total synthesis of waihoensene.
Recently, the Lee group has reported a synthetic methodology for the synthesis of tricyclic compounds from linear allenyl diazo substrates through tandem cycloaddition reaction sequence via TMM diyl.
In this article, they reported the method to construct tetracyclic compounds from substrates containing a six-membered ring by extending this synthetic methodology.
In this manner, they could introduce three contiguous stereogenic carbon centers and make tetracyclic structures which constitute the core skeleton for waihoensene. Thus, they accomplished the synthesis of waihoensene in four addtionaly steps from the product of this key step.
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