The Flu Pandemic of 1918

• The “Spanish flu” pandemic that swept around the world from June 1918 to December 1919 killed between 50 and 100 million people (3-6% of the global population).

• 10-20% of those infected with the H1N1 influenza virus died compared to the normal flu fatality rate of 0.1%.

• The swine flu outbreak of 2009 also involved the H1N1 virus, but that strain was not easily passed from person to person as occurred in the 1918 pandemic.

• Broad-spectrum antiviral agents are essential for defending against another severe flu strain while a vaccine is being developed.

• Oseltamivir (Tamiflu) and zanamivir (Relenza) are neuraminidase inhibitors. Neuraminidase is an enzyme whose action frees newly formed virus particles to infect other cells.

• Many governments have started stockpiling Tamiflu and Relenza as a precaution against another severe flu pandemic.

The Hayashi synthesis (Tokyo Univ. of Science) of Tamiflu

• Organocatalyis: chiral pyrrolidine-catalyzed reactions

• Cascade reactions• Curtiss rearrangement• Michael addtion and intramolecular Horner-

Wadsworth-Emmons reaction

Rubicordifolin and Rubioncolin B

• In 1990 and 1993, Itokawa et al. reported the isolation of a class of dimeric naphthodihydroquinones from the Chinese herb Rubia oncotricha and the Indian herb Rubia cordifolia.

• These natural products were unusual in that they were obtained as racemates, implying a nonenzymatic pathway in their biosynthesis.

• Dirk Trauner synthesized these compounds using a nonenzymatic dimerization strategy thought to mimic the biosynthesis.

Key Concepts

• Biomimetic synthesis• Cascade reactions• Diels-Alder cycloadditions