Time stereochemical analysis

The results from the cyclic series show that both oxygens come from the same side of tile double bond, probably from a single 0s04 molecule. The results in the acyclic series demonstrate that both oxygens add to the ends of the double bond at the same time. If one oxygen added first, an intermediate with a single carbon-carbon bond would be formed which could isomerize by rotation around that bond. The observation of complete diastereoselectivity requires that both C-0 bonds be formed simultaneously. Thus a concerted addition across the double bond is the most reasonable pathway consistent with these results. The stereochemical analysis is shown below for the cis starting material. 

Combining mechanisms with stereochemical analysis for the first time. 

In early studies the kinetics appeared to be sequential because of the convergence of double-reciprocal plots (72, 77). It was not entirely clear at the time that the phosphatase activity was an intrinsic part of the phosphotransferase activity, and the kinetics was not pursued further. Efforts to isolate an active phosphoenzyme failed, presumably due to its hydrolysis in the absence of a nucleoside 73, 77). The stereochemical analysis showing retention of configuration at phosphorus reopened the mechanistic question and stimulated further studies that... 

In Chapter 1 we discussed the synthesis of multistriatin (20), a pheromone of the elm bark beetle. The time has come for a stereochemical analysis of this problem. The molecule has four chiral centres ( in 20). One of them (a) turns out to be unimportant as disconnection of the acetal reveals (21) as the true-target. If (21) cyclises to form an acetal it must give (20)—no other stereochemistry is possible. 

Berchemia zeyheri (Rhamnaceae), a tree native to southern Africa which is prized for its beautiful wood, known as pink ivory or red ivory. The complexity of the phenolic compounds present in heartwood extracts prompted their analysis as permethylated derivatives. Stereochemical features were determined by using both NMR and circular dichroism spectroscopy of the parent compounds and their degradation products. These methods were used successfully to obtain a full stereochemical description of the zeyherin epimers 374 and 375, ° which were first isolated in 1971 but not fully characterized at that time. Subsequent work has led to the discovery of further auronol dimers and novel heterodimers with flavanone or isoflavanone constituents as summarized in Table 16.15. ° ° °... 

A gas chromatographic analysis of the product by the submitters using a 1.8-m. column packed with 20% Carbowax 20 M suspended on Chromosorb P and operated at 150° with a flow rate of 30 ml. per minute showed a peak for the major component having a retention time of 16 minutes and two minor peaks having retention times of 4 and 7 minutes, with relative areas amounting to 6% and 2% of the major peak, respectively. The stereochemical purity of the product was shown to be >95% cis by the submitters by gas chromatographic analysis using a 50-ft. capillary column... 

Nevertheless, when this article is continued after two decades, it should not remain restricted to stereochemical problems. During that time, other very powerful methods will have been developed which are mostly easier and often also more reliable. Particularly, the recent development in X-ray analysis gives a completely reliable proof of configuration valid even for the isolated molecule in the case of conformation it may appear necessary to prove that it is unchanged in solution (see for instance Reference 3). While X-ray is the most reliable method, NMR spectroscopy is the fastest. It still uses some empirical rules and comparison with model compounds, but in a modem version (2-D NMR, NOE) it is also completely trustworthy. Therefore, many recent dipole-moment studies investigated compounds whose steric arrangement was already known, and attention was focused on the electron distribution on the individual bonds, or in conjugated systems. The difference in the point of view may be explained as follows. 

In the 1980 s, we showed that THC-type compounds exhibit very high stereospecificity of cannabinoid action [20-24], Some of the previous observations regarding lack of stereospecificity were apparently due to separation problems. The (-)-enantiomer of d8-l 1-hydroxy-THC-DMH (3) (HU-210) (DMH=l,l-dimethylheptyl) was shown to be several thousand times more potent than the (-i-)-enantiomer (HU-211) (4) in a series of animal tests. The synthesis of HU-211 is presented in Figure 5.2 [25]. The intermediate (+)-4-oxo-myrtenyl pivalate (5), and its (-)-enantiomer are highly crystalline and can be obtained essentially stereochemically pure by recrystallization. This lucky observation made possible the ultimate synthesis of both enantiomers, HU-211 and HU-210, ine.e. higher than 99.8%, as determined by HPLC analysis of the respective diastereoisomeric bis-(S) (+)-a-methoxy-a-(trifluoro-methyl)phenyl-acetyl (MTPA) esters [25], Nonclassical cannabinoids were also shown to exhibit high stereospecificity of cannabinoid activity [21, 26]. 

Although mass spectrometry is a powerful and particularly sensitive tool in structural analysis, stereochemical aspects are more difficult to resolve by mass spectrometric means [ 1 ]. Of course, there do exist some time-honored examples for stereochemical effects showing up in mass spectra, and as a good example may serve the pronounced differences in the Retro-Diels-Alder (RDA) reactions of polycyclic compounds such as syn-1 and anti-l upon electron ionization (El) as shown in Scheme 1 [2]. 

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