Bioactivation reduction reactions

A chemical reduction, also based on a hydride transfer, was also developed the amino-reduction reaction. One example of such a reaction applied to a bioactive molecule is presented below (Figure 9.9). 

The last reaction perhaps involves an intermediate such as 33a which expells a proton and dimethyl sulfide. Formation of the Schiff s base with t-butylamine, reduction with sodium borohydride and hydrogenolysis of the benzyl ether produces sulfonterol (28). Despite the fact that the methylene hydrogen of sulfonterol must be much less acidic than of the corresponding urea proton on carbuterol or the sulfonamide proton on soterenol, good bioactivity is retained. 

Deprotection of X, and subsequent oxidation, reduction, and acetylation reactions can, with care, be carried out without decomposition of the inorganic backbone. Reactions of this type are of particular interest for the synthesis of bioactive or biocompatible polyphosphazenes. 

It has been proven that palladium catalyzed reductive Heck reactions are versatile and high-yield approach for preparing of new bioactive alkaloid epibatidine (1) analognes fromN-benzoylated 2-aza-bicyclo[2.2.1]hept-5-ene (3) and it has been shown that in case of aryl- groups reaction progresses regioselectively. All Heck type reactions proceed exo-selectively, leading to the same stereochemistry as fonnd in 1. 

Sulfahydantoins 87 and 88 are analogues of hydantoins and provide heterocyclic scaffolds with a great potential for the construction of bioactive compounds. A total of 28 derivatives, with crude purity generally higher than 85%, were prepared by parallel synthesis using an oxime resin as a solid support (Scheme 46) . The results constitute the first report of successful Mitsunobu reactions and reductive alkylations on the oxime resin. 

Furthermore, electron transfer (ET) to the 0-0 bond is believed to be critical to the bioactivities of the cyclic peroxides <2003CC1246> and the ET reaction chemistry of 3,3,6,6-tetraphenyl-l,2-dioxane 42 has been studied by cyclic voltammetry. Reaction products, besides the expected diol and benzophenone, were identified based on the standard reduction potentials and product analysis (Scheme 10). 

The metabolism of carbon tetrachloride (a chemical solvent that was formerly in common use) attracts attention as well. Its bioactivation appears to involve consecutive one-electron reduction and the formation of chloride ion and the trichloromethyl radical. The latter radical then reacts with oxygen, giving rise to an oxygenated radical and, eventually, to highly toxic phosgene (Mico Pohl 1983). Scheme 3-70 (below) describes these reactions ... 

When the last condensation reaction has occurred, the linear precursor needs to be released from the enzyme. For this important last step, several mechanisms are known simple hydrolysis of the thioester (balhimycin, vancomycin), intramolecular cyclization leading to a lactam (tyrocidine, bacitracin) or a lactone (surfactin), or even reductive thioester cleavage (linear gramicidin). In some cases, the linear precursor is dimerized (gramicidin S) or even trimerized (bacillibactin, enterobactin) before cyclization (Fig. 2). Even though these reactions are critical for the compound s bioactivity, the catalytic domains responsible for the release are not found in all NRPS systems and will therefore be called modifying domains. 

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