Alkene biological epoxidation

The Udenfiiend system of 1954 was perhaps the first to be specifically presented as a model of a biological process. In this system, Fe(II) is the catalyst, EDTA the ligand, air is the primary oxidant and ascorbic acid provides the reducing equivalents called for in this monooxygenase system. Arenes can be hydroxylated to phenols, alkanes to alcohols, and alkenes to epoxides, although with modest efficiency. The NIH shift was not observed in the model, however. 

Many naturally occurring substances are epoxides You have seen two examples of such compounds already m disparlure the sex attractant of the gypsy moth (Section 6 18) and m the carcinogenic epoxydiol formed from benzo[a]pyrene (Section 118) In most cases epoxides are biosynthesized by the enzyme catalyzed transfer of one of the oxy gen atoms of an O2 molecule to an alkene Because only one of the atoms of O2 is trans ferred to the substrate the enzymes that catalyze such transfers are classified as monooxy genases A biological reducing agent usually the coenzyme NADH (Section 15 11) is required as well... 

Chapter 7, Alkenes Reactions and Synthesis—Alkene epoxidation has been moved to Section 7.8, and Section 7.11 on the biological addition of radicals to alkenes has been substantially expanded. 

Sodium hexakis(formato)molybdate, 3, 1235 Sodium hypochlorite alkene epoxidation manganese catalysts, 6,378 Sodium ions biology, 6, 559 selective binding biology, 6, 551 Sodium molybdate, 3, 1230 Sodium peroxoborate, 3,101 Sodium/potassium ATPase, 6, 555 vanadate inhibition, 3, 567 Sodium pump, 6, 555 mechanism, 6, 556 Sodium pyroantimonate, 3, 265 Sodium salts... 

In addition to the unfunctionalized alkene epoxides discussed in the previous subsection, various other types of epoxides exist that are also derived from unconjugated alkenes but that share two additional features, i. e., being characterized by the presence of one or more functional group(s) and having biological significance. Thus, the present subsection examines epoxy alcohols, epoxy fatty acids, allylbenzenes 2, 3 -oxides, as well as alkene oxide metabolites of a few selected drugs. 

Polyamino acids are easy to prepare by nucleophUe-initiated polymerisation of amino acid JV-carboxyanhydrides. Polymers such as poly-(L)-leucine act as robust catalysts for the epoxi-dation of a wide range of electron-poor alkenes, such as y-substituted a,Ji-unsaturated ketones. The optically active epoxides so formed may be transformed into heterocyclic compounds, polyhydroxylated materials and biologically active compounds such as dUtiazem and taxol side chain. 

Preparation of nonracemic epoxides has been extensively studied in recent years since these compounds represent useful building blocks in stereoselective synthesis, and the epoxide functionality constitutes the essential framework of various namrally occurring and biologically active compounds. The enantiomericaUy enriched a-fluorotropinone was anchored onto amorphous KG-60 silica (Figure 6.6) this supported chiral catalyst (KG-60-FT ) promoted the stereoselective epoxidation of several trans- and trisubstituted alkenes with ees up to 80% and was perfectly reusable with the same performance for at least three catalytic cycles. 

Apart from the catalytic properties of the Mn-porphyrin and Mn-phthalo-cyanine complexes, there is a rich catalytic chemistry of Mn with other ligands. This chemistry is largely bioinspired, and it involves mononuclear as well as bi- or oligonuclear complexes. For instance, in Photosystem II, a nonheme coordinated multinuclear Mn redox center oxidizes water the active center of catalase is a dinuclear manganese complex (75, 76). Models for these biological redox centers include ligands such as 2,2 -bipyridine (BPY), triaza- and tetraazacycloalkanes, and Schiff bases. Many Mn complexes are capable of heterolytically activating peroxides, with oxidations such as Mn(II) -> Mn(IV) or Mn(III) -> Mn(V). This chemistry opens some perspectives for alkene epoxidation. 

The next step is simple—the epoxidation of one of the terminal double bonds—but it leads to two of the most remarkable reactions in all of biological chemistry. Squalene is not chiral, but enzymatic epoxidation of one of the enantiotopic alkenes gives a single enantiomer of the epoxide with just one stereogenic centre. 

The activation of oxygen in oxygen transfer reactions is usually mediated by a suitable transition metal catalyst which has to be sufficiently stable under the reaction conditions needed. But also non-metal catalysts for homogeneous oxidations have recently been of broad interest and several of them have been compiled in a recent review.2 Other examples for well known alkene oxidation reactions are the ozonolysis, hydroboration reactions or all biological processes, where oxygen is activated and transferred to the substrate. Examples for these reactions might be cytochrome P450 or other oxotransferases. Of these reactions, this contribution will focus on transition-metal mediated epoxidation and dihydroxylation. 

Biological systems overcome the inherent unreactive character of 02 by means of metalloproteins (enzymes) that activate dioxygen for selective reaction with organic substrates. For example, the cytochrome P-450 proteins (thiolated protoporphyrin IX catalytic centers) facihtate the epoxidation of alkenes, the demethylation of Al-methylamines (via formation of formaldehyde), the oxidative cleavage of a-diols to aldehydes and ketones, and the monooxygenation of aliphatic and aromatic hydrocarbons (RH) (equation 104). The methane monooxygenase proteins (MMO, dinuclear nonheme iron centers) catalyze similar oxygenation of saturated hydrocarbons (equation 105). ... 

Another biologically important epoxide is disparlure (4), the pheromone of the gypsy moth. This economically important insect epoxidizes a straight-chain alkene to produce just one enantiomer. The epoxide is required to be displayed as a single enantiomer to be attractive59. 

Epoxidation of the cis alkene A from two different sides of the double bond affords two cis epoxides in the last step—a racemic mixture of two enantiomers. Thus, half of the product is the desired pheromone disparlure, but the other half is its biologically inactive enantiomer. Separating the desired from the undesired enantiomer is difficult and expensive, because both compounds have identical physical properties. A reaction that affords a chiral epoxide from an achiral precursor without forming a racemic mixture is discussed in Section 12.15. 

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