CHED 420 |
| The perhydroisoquinoline structure is commonly found in a wide variety of biologically active and chemically interesting alkaloids including the anti-retrovirals nelfinavir and saquinavir utilized in HIV drug regimes. With a Van der Waals radius only marginally larger than hydrogen and the greatest electronegativity of any element, fluorine is well known for enhancing the parent molecule's pharmokinetic properties making fluorine a key functionality in medicinal chemistry. Thus, the introduction of fluorine into the common perhydroisoquinoline ring system represents an interesting possibility for the synthesis of non-natural, biologically active compounds. Herein is presented work towards the synthesis of a gem-difluoro perhydroisoquinoline core. A three step sequence starting with gem-Difluorohomopropargyl bromide (1) provides ene-yne (2), which then undergoes a cycloisomerization catalyzed by a Hoveyda-Grubbs 2nd generation catalyst. A Diels-Alder cycloaddition of 3 leads to 4, from which it is only a few steps to the gem-difluoro-perhydroisoquinoline core (5).
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Undergraduate Research Poster Session: Organic Chemistry
11:00 AM-1:00 PM, Monday, April 7, 2008 Morial Convention Center -- Hall A, Poster
Division of Chemical Education |
