The Flu Pandemic of 1918

1. 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.

2. 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.

3. 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

12. Rubicordifolin and Rubioncolin B • In 1990 and 1993, Itokawa et al. reported the isolation of a class of dimericnaphthodihydroquinones from the Chinese herb Rubiaoncotrichaand the Indian herb Rubiacordifolia. • 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.

13. Key Concepts • Biomimetic synthesis • Cascade reactions • Diels-Alder cycloadditions