Cyanogen bromide elimination

Independent synthesis of IQ, eliminating the alkylating reaction step, involved the cyclizations of 7-R-5-amino-6-methylaminoquinolines with cyanogen bromide. When " C-labeled BrCN was used, the corresponding 2- " C-labeled analogues of IQ and MelQ were synthesized (83ACSI57). The diamines are available from 5-nitroderivatives, which in turn have been prepared by nitration of methylami-noderivatives (82CPB1857). 

Treatment of MFA (1) with cyanogen bromide [6] opened ring G to yield the bromo derivative 3 [7]. Attempts to dehydrobrominate 3 in one step via a base-catalyzed elimination with DBU/CH3CN, KOH/MeOH, or terr-BuOK/DMSO were unsuccessful. However, the required methylene entity could be introduced by converting 3 first to a selenide, then oxidation with periodate, followed by thermolysis in benzene to provide compound 4. Hydrolysis of the cyano group with NaOH in ethylene glycol [8] produced 5 (50% yield). Osmium catalyzed oxidation of 5 in the presence of 4-methylmorpholine A-oxide (NMO) gave a diol, which was cleaved to an aldehyde upon treatment with periodate. Treatment of the aldehyde with sodium cyanoborohydride resulted in an intramolecular reductive animation to yield the desired product PHB (6). 

Immunoaffinity chromatography cleanup has also been applied as an ideal and reliable strategy for residue analysis. Immunoaffinity columns prepared by coupling the antibodies to a cyanogen bromide-activated support were used to analyze avermectin BI residues in cattle tissues (359) and ivermectin in sheep serum (376). An immunoaffinity column prepared by an alternative activation/ coupling procedure with carbonyl diimidazole was also employed to analyze ivermectin residues in swine liver (361) since the earlier-reported methods did not work well in the analysis of this matrix. This recent work demonstrated the high specificity of tire antibody-mediated cleanup, but also showed that the immunoaffinity procedures could not always or completely eliminate matrix interference of samples. Therefore, application of additional cleanup steps before or after these procedures is often inevitable. 

Cocaine, a levorotatory crystalline base, is a tertiary amine that forms a methiodide with one mole of methyl iodide (100). Methyl bromide is eliminated from Z-cocaine by cyanogen bromide (165a) in the formation of cyanonorcocaine. Z-Cocaine must therefore contain the characteristic... 

A variation on this theme is the cyanogen bromide or chloroformate ester-mediated rupture of the fusion bond, accompanied by elimination. An example is the synthesis of the strained naph-thaleno-fused azonine (260) from the tetracycle (261) reported by Bremner et al. (Equation (31)) <85JA3910> (see also <85H(23)i45l, 86JOC3295 . A similar approach has been used by Danishefsky and co-workers in their total synthesis of indolizomycin <90JA2003>. 

A related reaction, elimination of an alkyl bromide from a pentavalent cyanogen bromide adduct, has been a useful means of preparing cyano-arsines (236). 

Other Matrices. A large number of other matrices have been employed, including starch (33), cross-linked dextrins (34,35), a vinyl maleimide polymer (36), chitin (37), mannan (38), and insolubilized proteins (39). The number of potential matrices is almost limitless, and most of the matrices used for immobilization of enzymes have potential application in bioselective adsorption. Among these are nylon (40), metal oxides (41), maleic anhydride-ethylene co-polymers (42), and polystyrene derivatives (43). Few of these have been used because of their potential for nonspecific adsorption either by charge, as with the metal oxides, or by hydrophobic interactions (as would be the case with polystyrene). The derivatized matrix must be free of nonspecific adsorption. Proper derivatization can eliminate nonspecific adsorption or, as with cyanogen bromide activation, create nonspecific adsorption in matrices having no prior nonspecific adsorption properties. 

Stereospecific synthesis of c/5-disubstituted or trisubstituted olefins from mono- or di-substituted alkynes can be accomplished via hydroboration to dialkylvinylboranes followed by addition of sodium hydroxide and iodine. By treatment of the vinylborane with cyanogen bromide in methylene chloride solution, the complementary procedure, namely conversion into the /ra 5-olefin, may be effected. In the c/j-producing case, the stereochemistry is believed to be the result of /m 5-elimination of iodide and boron from the intermediate (64). In the corresponding intermediate (65) produced using... 

Neostrychnine. Neither the Hofmann, Emde, or cyanogen bromide reactions have been particularly useful as starting points for systematic degradations of strychnine because of the stereochemistry which is not suitable for eliminations and instead a multiplicity of Sn2 products were usually formed. It was a study of the Hofmann degradation that first led to neostrychnine (Chart 6.4), a double bond isomer (J20,2i Qf strychnine, a compound more readily made by heating strychnine with selenium or Raney... 

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