Natural Product-Derived Chiral Pyrrolidine-2,5-diones, Their Molecular Structures and Conversion to Pharmacologically Important Skeletons

The versatility of the natural products
(2S,3S)- and (2S,3R)-3-hydroxy-5-oxotetrahydrofuran-2,3-dicarboxylic
acids (1 and 2), isolated in large amounts
from tropical plant sources, has been demonstrated by the construction
of 3-substituted and 3,4-disubstituted chiral pyrrolidine-2,5-diones.
The absolute configurations of chiral pyrrolidine-2,5-diones have
been ascertained using chiroptical spectroscopic methods and/or single-crystal
XRD data. A combination of different reaction strategies delivering
a diverse matrix of fused heterocyclic ring systems is presented.
The pyrrolo­[2,1-a]­isoquinoline alkaloid (+)-crispine
A possesses a wide range of pharmacological activities including antidepressant,
antiplatelet, antileukemic, and anticancer activities. The analogues
of indolizino­[8,7-b]­indole alkaloids (+)- and (−)-harmicine
show strong antileishmanial, antinociceptive, PDE5-inhibitory, antimalarial,
and antiviral activities. The bicyclic furo­[2,3-b]­pyrrolo skeleton is present in many natural products. Thus, the
uniqueness of relatively cheap, naturally occurring chiral 2-hydroxycitric
acid lactones as chirons has been demonstrated by the construction
of some important molecular skeletons that are otherwise difficult
to synthesize.