Finally, parvaquone 1 was synthesized by treating 6 with an excess of BBr3 to yield a yellow crystalline solid with identical spectral properties as those reported previously (eq. 4).4
(Z) OOi-Pr-O61, 81% (1) 2.5 eq. BBr3/-78 °C/CH2Cl2(2) H2O, -78 °C(4)
In conclusion, a straightforward synthesis of parvaquone was developed with a 26% overall yield. Most of the steps in the synthetic sequence are efficient and the starting materials are either commercially available or readily prepared. Moreover, this method offers the possibility for the preparation of a host of parvaquone analogues by the addition of aryllithium derivatives with different substitution patterns.
Experimental Section
General Procedures. 1H NMR spectra were recorded on a Varian Gemini 200 (200 MHz) spectrometer in deuteriochloroform (CDCl3) with either tetramethylsilane (TMS) (0.0 ppm) or chloroform (7.26 ppm) as internal reference unless otherwise indicated. Data are reported in the following order: chemical shift in ppm (d), multiplicities (br (broadened), s (singlet), d (doublet), t (triplet), q (quartet), sex (sextet), hep (heptet), m (multiplet), exch (exchangeable), app (apparent)), coupling constants, J, are reported (Hz), and integration. Infrared spectra were recorded on a Perkin-Elmer FTIR 1600 series spectrophotometer. Peaks are reported (cm-1) with the following relative intensities: s (strong, 67-100%), m (medium 40-67%), and w (weak 20-40%).
Analytical thin-layer chromatography was performed on Merck silica gel plates with F-254 indicator. Acid-pretreated silica gel plates were used to monitor the final deprotection of 2. Visualization was accomplished by UV-light, iodine, or p-anisaldehyde solution. Medium pressure liquid chromatography (MPLC) was performed as described by Baeckström et al.9 using gradient solutions with the indicated solvent systems. THF was dried over sodium and stored over activated 4Å molecular sieves. All reactions were performed under a dry N2 atmosphere in oven- and or flame-dried glassware.
Commercial chemicals. The following materials were obtained from commercial sources: C6H11MgCl, PhLi, TFAA, and BBr3.
