Epoxides in biological processes

Although nucleophilic participation at the transition state is slight, it is enongh to ensure that substitution proceeds with inversion of configuration. 

PROBLEM 16.14 Which product, compound A, B, or C, would you expect to be formed when 1-methyl-1,2-epoxycyclopentane of the absolute configuration shown is allowed to stand in methanol containing a few drops of sulfuric acid Compare your answer with that given for Problem 16.13. 

A method for achieving net anti hydroxylation of alkenes combines two stereo-specihc processes epoxidation of the donble bond and hydrolysis of the derived epoxide. 

PROBLEM 16.15 Which alkene, c/s-2-butene or frans-2-butene, would you choose in order to prepare meso-2,3-butanediol by epoxidation followed by acid-catalyzed hydrolysis Which alkene would yield meso-2,3,-butanediol by osmium tetraoxide hydroxylation  

Many naturally occurring substances are epoxides. You have seen two examples of such compounds already in disparlure, the sex attractant of the gypsy moth (Section 6.18), and in the carcinogenic epoxydiol formed from benzo[a]pyrene (Section 11.8). In most cases, epoxides are biosynthesized by the enzyme-catalyzed transfer of one of the oxygen atoms of an O2 molecule to an alkene. Since only one of the atoms of O2 is 

A prominent example of such a reaction is the biological epoxidation of the polyene squalene. 

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Model computational studies aimed at understanding structure-reactivity relationships and substituent effects on carbocation stability for aza-PAHs derivatives were performed by density functional theory (DFT). Comparisons were made with the biological activity data when available. Protonation of the epoxides and diol epoxides, and subsequent epoxide ring opening reactions were analyzed for several families of compounds. Bay-region carbocations were formed via the O-protonated epoxides in barrierless processes. Relative carbocation stabilities were determined in the gas phase and in water as solvent (by the PCM method). 

Epoxides also are important in biological processes because they are reactive enough to be attacked by nucleophiles under the conditions found in living systems (Section 12.8). 

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. 

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. 

The opening of epoxide rings with nucleophiles is a key step in some important biological processes. 

PROBABLE FATE photolysis direct photolysis may be important oxidation probably not important, photooxidation by u.v. light in aqueous medium 90-95°C, formation of CO2 25% took 2.9 hr, 50% took 4.8 hr, 75% took 12.5 hr, photooxidation half-life in air 4 hrs-1.7 days hydrolysis hydrolysis of epoxide, too slow to be important, first-order hydrolytic half-life 10.5 yrs volatilization volatilization is an important process, volatilization 25°C from soils in lab sandy loam 8.9% after 60 days, sand 34.2% after 60 days, calculated half-life in water based on an evaporation rate of 5.33x10m/hr 12,940 hr sorption probably an important process, will adsorb strongly to sediments once it reaches surface water biological processes moderate bioaccumulation... 

Cytochrome P-450 is a heme-containing monooxygenase that catalyzes a number of important substrate oxidations, including hydroxylation of alkanes and epoxidation of alkenes. These transformations are an important part of the metabolic processes involved in the formation of biologically active compounds from lipids and aromatics, and for the excretion of exogenous compounds in detoxification processes. The stoichiometric reaction of cytochrome P-450 is given in equation 1. 

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