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Rubicordifolin is a natural product that is produced by Rubia cordifolia, a plant that is a member of the Rubiaceae family. The molecule is isolated from the roots of Rubia cordifolia and was first characterized in 1993. In 2004, the first synthesis of rubicordifolin was accomplished. The molecule has been shown to have both cytotoxic and antitumor properties.
Contents
Biosynthesis
A biosynthetic pathway for rubicordifolin has yet been elucidated. However, it has been hypothesized that the dimerization of the two napthoquinone units yields rubicordifolin. Napthoquinones can be traced back to the shikamate pathway in plants. Shikamate is converted into chorismic acid, which is further converted into 2-succinylbenzoic acid through a TPP dependent reaction.
After 2-succinylbenzoic acid has been produced, a cyclization, a prenylation, a methylation, and an oxidation occur which yields a napthoquinone.
Once this napthoquinone has been made, a series of oxidations and cyclizations lead to two substrates that can undergo a [4+2] cycloaddition that leads to the product.
Synthesis
The Trauner group at UC Berkeley completed a synthesis of rubicordifolin in 2004. The synthesis of the natural product, dubbed a “biomimetic” synthesis, takes inspiration from the proposed dimerization of two napthoquinones units. Mechanistically, it is proposed that the phenylboronic acid promotes a cyclization that is followed by a Diels-Alder reaction to yield the final product.
Pharmacology
Studies of rubicordifolin demonstrate that the natural product possesses both cytotoxic and antitumor properties. When tested against Chinese hamster lung fibroblasts, human nasopharynx carcinomas, and lymphocytic leukemia cells, rubicordifolin exhibited cytotoxic activities (measured in IC50, μg/ml) of 4.7, 2.9, and 1.2 respectively.