The structural complexity and biological activity of the
cyathane family of diterpenes has stimulated considerable
interest from synthetic chemists. Testimony to this has been
recorded in the number and diversity of approaches that have
been developed to construct these fascinating natural prod-
ucts.10
Our own strategy for cyathane synthesis is based on the
retrosynthetic analysis illustrated in Scheme 1. We reasoned
Figure 1. Representative cyathane diterpenes.
Scheme 1
is a neurotrophin protein dimer that is essential for the
development and maintenance of neuronal cells.7 Delivery
of NGF to the brain represents a potential approach for the
treatment of neurodegeneration in Alzheimer, Parkinson, and
Huntington diseases; however, it requires invasive surgical
techniques because NGF does not cross the blood-brain
barrier and is rapidly metabolized in vivo.8 As an alternative,
the use of small-molecule NGF promoters is currently
perceived as a promising way to treat these neurodegenera-
tive diseases.9
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that the tricyclic core of cyathanes shown here with (+)-
allocyathin B2 could be derived from tricycle A. This
precursor could in turn originate from a transition-metal-
catalyzed intramolecular [5 + 2] cycloaddition of a vinyl-
cyclopropane with a π-system as found in B. Further analysis
suggests that B could be elaborated from cyclopentane
carboxaldehyde 5, which could ultimately be traced back to
commercially available and inexpensive (S)-(-)-limonene.
Following this plan, the synthesis of the cyclopentanone
6 was achieved through a shortening of previously published
routes.11 Aldehyde 4 was obtained in three steps and 68%
yield by partial hydrogenation of (S)-(-)-limonene over
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