8676
Acknowledgements
This work was supported by grants from the National Institutes of Health (grant GM 28961)
and Pfizer, Inc.
References
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9. A representative experimental procedure is summarized here for the preparation of 2c: DMAP (0.2680 g, 2.19
mmol), DMAP·HCl (0.3575 g, 2.25 mmol)10 and PS-carbodiimide (1.9547 g, 2.15 mmol) were dissolved in
ethanol-free chloroform (25 mL)10 in a flame dried 50 mL round-bottomed flask equipped with a condenser and
stir bar. The mixture was then brought to reflux, and a solution of 15-hydroxypentadecanoic acid (0.0557 g, 0.216
mmol) in dry THF (5 mL) was added via syringe pump over 14 h. A gastight syringe and Teflon tube were used
with the Teflon tube inlet placed in the condensate formed at the tip of the reflux condenser. A TLC taken after
the addition was completed (50% ethyl acetate in hexanes, Rf 0.78) showed no starting material. The syringe and
Teflon tube were rinsed to recover 10.4 mg of hydroxy acid. The reaction mixture was cooled to rt, filtered using
a sintered glass funnel, concentrated to approximately 5 mL, diluted with 20 mL of ether, filtered through a pad
of Celite, and concentrated. The crude product was purified by flash chromatography (using a 24×1.5 cm column,
packed in hexanes, eluted with 20 mL of hexanes followed by 3% THF in hexanes, collecting 6 mL fractions).
Concentration of fractions 14–16 yielded 41.1 mg (97%, based on hydroxy acid delivered to the reaction) of
lactone. Concentration of fractions 17–22 yielded 1.1 mg of diolide.
10. DMAP·HCl is easily prepared by passing anhydrous HCL into a solution of DMAP in THF and collecting the
precipitate. The CHCl3 used was EM Science ‘OmniSolve’ and contains a hydrocarbon stabilizer; alternatively,
ethanol-free CHCl3 can be prepared as described in the following: Perrin, D. D.; Armego, W. L.; Perrin, D. R.,
Eds. Purification of Laboratory Chemicals; Pergamon: Oxford, 1966.
.