A rapid, asymmetric synthesis of the decahydrofluorene core of the hirsutellones.
A tandem ketene-trapping/Diels-Alder cyclization sequence was the pivotal transformation in an efficient, asymmetric synthesis of a decahydrofluorene tricyclic structure possessing eight stereogenic centers and key features of the hirsutellone class of antitubercular natural products. The hirsutellone-like beta-keto ester that was fashioned by this sequence (13 steps; 6% overall yield) demonstrated significant inhibitory activity against Mycobacterium tuberculosis. The mechanism of action of this antitubercular compound is not yet known.
Tilley
S David
SD
Department of Chemistry, Princeton University, Frick Chemical Laboratory, Princeton, New Jersey 08544, USA.
Reber
Keith P
KP
Sorensen
Erik J
EJ
D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003500:Cyclization; D005449:Fluorenes / Q000138:chemical synthesis* / Q000737:chemistry; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects
D000995:Antitubercular Agents; D005449:Fluorenes; D006576:Heterocyclic Compounds, 4 or More Rings