Brominated natural compounds

Covaci, A., Voorspoels, S., Ramos, L., Neels, H., Blust, R. (2007a) Recent developments in the analysis of brominated flame retardants and brominated natural compounds. J. Chromatog. A, 1153 145-171. 

In spite of the fact that biotechnology rather than chemical processing will probably provide the future greatly needed chirally pure compounds (ref. 1), we believe that simple chemical reactions starting from chiral natural compounds and proceeding under stereochemical control will eventually retain full importance. On the above grounds, we report on simple reactions which start from a-aminoacids, as an example of utilization of natural compounds, and move to related bromine containing compounds (Fig. 1). 

Although the process as it stands is still not enantioselective in nature, the high yield and mild reaction conditions may attract further search for an asymmetric version of this reaction using proper chiral bromine-comtaining compounds as the catalyst. 

The addition of a mass-signature element that contains a 1 1 ratio of one or more stable isotopes ( C, N. or H) splits the molecular ion into two equal peaks (similar to bromine). All compounds that contain the peak-splitting component are easily recognized in the spectrum as goalpost-like peaks separated by the mass difference between the natural and isotopically labeled components. The peak-splitting element provides a valuable means for recognition of the compounds synthesized on the solid phase. 

Numerous chlorine, fluorine, and bromine-containing compounds (halocarbons) are produced at the Earth s surface, both by natural and... 

Although the fragmentation patterns we have described are well characterized, the most interesting feature of the mass spectra of chlorine- and bromine-containing compounds is the presence of two molecular ion peaks. As Section 8.4 indicated, chlorine occurs naturally in two isotopic forms. The natural abundance of chlorine of mass 37 is 32.5% that of chlorine of mass 35. The natural abundance of bromine of mass 81 is 98.0% that of Br. Therefore, the intensity of the M -I- 2 peak in a chlorine-containing compound should be 32.5% of the intensity of the molecular ion peak, and the intensity of the M -I- 2 peak in a bromine-containing compound should be almost equal to the intensity of the molecular ion peak. These pairs of molecular ion peaks (sometimes called doublets) appear in the mass spectra of ethyl chloride (Fig. 8.49) and ethyl bromide (Fig. 8.50). 

In hindsight, this is remarkable in several respects. For one, purple stands out as one of the first known examples of natural brominated organic compounds. For another, the substitution pattern is unusual bromination of indigo in nitrobenzene gives 5,5 -, not 6,6 -dibromoindigo. 

The advantage of stable isotope patterns for metabolite identification is the ease of identification of metabolites with the same specific isotope patterns as parent drug in a complex biological sample. For example, chlorine and bromine exhibit unique natural isotopic patterns. Chlorine or bromine-containing compounds will have similar isotopic ratio patterns arising from Cl Cl... 

A method of synthesis which should prove useful for the preparation of carboxyl-labeled linoleic acid has been recently announced by Howton and co-workers (1952). In this procedure tetrabromstearic acid was produced by bromination of natural linoleic acid. After decarboxylation of the silver salt of the tetrabrom-acid with bromine, the compound was debrominated with zinc, and the linoleic acid was regenerated with a new carboxyl group by means of the Grignard reagent with CO. ... 

Chlorinated and brominated organic compounds that come from natural sources are... 

Many polycyclic natural compounds that contain bromine atoms have been isolated from several different marine organisms (Fig. 9.3) [7, 8]. Most of them possess bioactivities of pharmacological interest such as antibacterial, anticancer, antifungal, anti-inflammatory, and antiviral activities. Natural products that have an a-bromo-p,p-dimethylcyclohexane structure are also bioactive compounds. Their biosynthesis... 

Isotopic clusters are especially apparent when atoms such as bromine and chlorine are present m an organic compound The natural ratios of isotopes m these elements are... 

For other elements that occur with major relative abundances of more than one isotope in the natural state, the isotope pattern becomes much more complex. For example, with chlorine and bromine, the presence of these elements is clearly apparent from the isotopes Cl and for chlorine and Br and Br for bromine. Figure 47.2a shows the molecular ion region for the compound chlorodecane. Now, there are new situations in that C, C, C1, and Cl isotopes all have probabilities of occurring together. Thus, there are molecular ion peaks for + Cl, C + Cl, + Cl, and so on. Even so, the isotopic ratio of 3 1 for Cl to Cl is very clear... 

Dissolved Minerals. The most significant source of minerals for sustainable recovery may be ocean waters which contain nearly all the known elements in some degree of solution. Production of dissolved minerals from seawater is limited to fresh water, magnesium, magnesium compounds (qv), salt, bromine, and heavy water, ie, deuterium oxide. Considerable development of techniques for recovery of copper, gold, and uranium by solution or bacterial methods has been carried out in several countries for appHcation onshore. These methods are expected to be fully transferable to the marine environment (5). The potential for extraction of dissolved materials from naturally enriched sources, such as hydrothermal vents, may be high. 

An asymmetric synthesis of estrone begins with an asymmetric Michael addition of lithium enolate (178) to the scalemic sulfoxide (179). Direct treatment of the cmde Michael adduct with y /i7-chloroperbenzoic acid to oxidize the sulfoxide to a sulfone, followed by reductive removal of the bromine affords (180, X = a and PH R = H) in over 90% yield. Similarly to the conversion of (175) to (176), base-catalyzed epimerization of (180) produces an 85% isolated yield of (181, X = /5H R = H). C8 and C14 of (181) have the same relative and absolute stereochemistry as that of the naturally occurring steroids. Methylation of (181) provides (182). A (CH2)2CuLi-induced reductive cleavage of sulfone (182) followed by stereoselective alkylation of the resultant enolate with an allyl bromide yields (183). Ozonolysis of (183) produces (184) (wherein the aldehydric oxygen is by isopropyUdene) in 68% yield. Compound (184) is the optically active form of Ziegler s intermediate (176), and is converted to (+)-estrone in 6.3% overall yield and >95% enantiomeric excess (200). 

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