Global fitting

CHARACTERIZING QUINONE METHIDES BY SPECTRAL GLOBAL FITTING AND 13 C LABELING... 

Using Spectral Global Fitting to Study Transient Quinone Methides... 

Our studies of quinone methides and related species using 13C labeling and spectral global fitting started in the late 1990s and have continued to the present with two papers on prekinamycins slated for publication in 2009. In this section, we summarize what we learned from both our published and unpublished studies. 

We studied the reactions shown in Scheme 7.18 using the global fitting methodology described in Section 7.2.1. The quinone methide species rapidly built up in solution upon quinone reduction and trapped by either water or a proton to afford the final products shown in Scheme 7.18. global fitting provided the rates of quinone methide... 

The global fitting studies revealed that the hydroquinone species shown in Scheme 7.5 affords the quinone methide at rates of 1-2 x 10 3 min-1 that are independent of both pH (from 7 to 9.5) and the concentration of buffers used to hold pH. We interpreted this observation as protonation of the C-5 center followed by the slow loss on the nitrogen-leaving group. The anionic C-5 center of the electron-rich hydroquinone ring would be very basic resulting in complete protonation near neutrality. 

FIGURE 7.24 Spectra obtained from spectral global fitting to the surface shown in Fig. 7.2 spectrum of quinone at zero time and the spectrum of the quinone methide intermediate. 

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