Chemical synthesis epoxide

Enzymatic hydrolysis of A/-acylamino acids by amino acylase and amino acid esters by Hpase or carboxy esterase (70) is one kind of kinetic resolution. Kinetic resolution is found in chemical synthesis such as by epoxidation of racemic allyl alcohol and asymmetric hydrogenation (71). New routes for amino acid manufacturing are anticipated. 

By employing Sharpless epoxidation as a key step, a multistep chemical synthesis of (E)-pantolactone has also been reported (55). 

Studies on the comparative abilities (13) of B[a]P metabolites to bind to DNA in microsomal systems showed that the 7,8-dihydrodiol was the most efficient. This led to the proposal (69) that dihydrodiol epoxides were the ultimate carcinogenic metabolites. Chemical synthesis of all possible isomers (70.71) has allowed complete structural identification of the adducts (72-74). 

In the application of the above discovery, ( )-3-benzyloxy-2-methyl pro-pionaldehyde 52 is used as the starting material in the synthesis of rifamycin A. As outlined in Scheme 7-12, compound 52 is converted to allyic alcohol 55 via a series of chemical reactions. Epoxidation of 55 proceeded stereoselectively, giving a single epoxide that affords 57 after subsequent treatment. Compound 57 may be converted to 58 upon acetonide formation. 

In spite of the potential interest of such enzymes for fine chemical synthesis, it was only recently that a detailed search for epoxide hydrolases from microbial... 

Miscellaneous Iminium Catalyzed Transformations The enantioselective construction of three-membered hetero- or carbocyclic ring systems is an important objective for practitioners of chemical synthesis in academic and industrial settings. To date, important advances have been made in the iminium activation realm, which enable asymmetric entry to a-formyl cyclopropanes and epoxides. In terms of cyclopropane synthesis, a new class of iminium catalyst has been introduced, providing the enantioselective stepwise [2 + 1] union of sulfonium ylides and ot,p-unsaturated aldehydes.As shown in Scheme 11.6a, the zwitterionic hydro-indoline-derived catalyst (19) enables both iminium geometry control and directed electrostatic activation of sulfonium ylides in proximity to the incipient iminium reaction partner. This combination of geometric and stereoelectronic effects has been proposed as being essential for enantio- and diastereocontrol in forming two of the three cyclopropyl bonds. 

The catalytic asymmetric epoxidation of a,p-unsaturated aldehydes has also been an important challenge in iminium catalysis and for chemical synthesis in general. More recently, Jprgensen and coworkers have developed an asymmetric organocatalytic approach to ot, (3-epoxy aldehydes using pyrrolidine catalyst 20 and H2O2 as the stoichiometric oxidant. The reaction appears to be extremely general and will likely receive wide attention from the chemical synthesis community (Scheme 11.6b). 

Carbon dioxide is a widely available, inexpensive, and renewable resource. Hence, its utilization as a source of chemical carbon or as a solvent in chemical synthesis can lead to less of an impact on the environment than alternative processes. The preparation of aliphatic polycarbonates via the coupling of epoxides or oxetanes with CO2 illustrates processes where carbon dioxide can serve in both capacities, i.e., as a monomer and as a solvent. The reactions represented in (1) and (2) are two of the most well-studied instances of using carbon dioxide in chemical synthesis of polymeric materials, and represent environmentally benign routes to these biodegradable polymers. We and others have comprehensively reviewed this important area of chemistry fairly recently. Nevertheless, because of the intense interest and activity in this discipline, regular updates are warranted. 

In the example of the asymmetric epoxidation of olefins, enzymes, synthetic catalysts, and catalytic antibodies have been compared side-by-side with respect to performance in chemical synthesis (Jacobsen, 1994). Epoxidation of olefins is a reaction of considerable industrial interest where, historically, enzymes have not performed extremely well. One reason is the dependence of the enantiomeric purity of the diol and epoxide products on the regiospecificity of the attack on the racemic epoxide by a water molecule (Figure 20.1). 

Scheme 9.4 Problems encountered during opening of typical epoxide intermediate (see also Section 9.4, Chemical Synthesis) when intended N-external ester substituents do not bear alpha-substituents [10]. A Normal, well-behaved reaction as typically deployed for beta-blockers wherein the N-alkyl group bears an alpha-substituent as most commonly represented by isopropylamine. B The over-alky-lation problem that occurs significantly when the N-alkyl group is not alpha-substituted. Also note that when n = 3 or 4, the first alkylation is instead followed immediately by an intramolecular ring-closure reaction to form the five- or six-membered lactam. These unwanted side products, although readily...

The most widely studied aspect of arene-oxide chemistry is the aromatization reaction to yield phenols. The acid-catalyzed, spontaneous, and thermal rearrangements of epoxides to ketones have a parallel in the isomerization of arene oxides to dienone intermediates with subsequent aromatization to phenols. Prior to their availability by chemical synthesis, arene oxides were postulated as initial inter-... 

Reactions with aliphatic and aromatic epoxides. The metabolism of many alkenes and arenes Is known to proceed via epoxides formed by phase I reactions (166). Chemical methods for the preparation of epoxides will not be discussed here but valuable references (or references cited therein) for their synthesis are found In Table VII. The electrophilic character of the epoxides has been utilized In chemical synthesis of several PMAF metabolites. Differences In the reactlvltes of arene oxides are probably less Important In chemical synthesis of their conjugates but may Influence the ratio of positional and dlasteromers formed. The reaction of GSH with a xenobiotic epoxide gives the 1,2-dlhydro--l-hydroxy-2-glutathlonyl-xenoblotlc conjugate and with cysteine and N-acetyl-cystelne the corresponding dlhydro-hydroxy conjugates. The nucleophile (GSH, cysteine or N-acetyl-cystelne)... 

Peracids are not used as initiators they are applied in chemical synthesis as epoxidation reagents or in disinfection (Table 1). For decomposition schemes of various classes see Figs. 4—9. 

In spite of the considerable value of epoxide hydrolases for fine chemical synthesis, it was only recently that a detailed search for epoxide hydrolases from microbial sources was undertaken by the groups of Furstoss185, 901 and Faber123, 79, 911, bearing in mind that the use of microbial enzymes allows an (almost) unlimited supply of biocatalyst. The screening was based along the following considerations on the one hand, the catabolism of alkenes often implies the hydrolysis of an epoxide inter-... 

The microbial transformation of humulene, a substrate showing a structure similar to that of germacrone, was studied by Abraham and Stumpf using a screen of about 300 strains1175 . This led the authors to select the fungi Diplodia gossypina and Chaetonium cochlioides for preparative scale experiments. It was thus observed that the main reaction path starts with the epoxidation of the 1,2-double bond, as shown by direct biotransformation of this monoepoxide obtained by chemical synthesis. This is then further oxidized to yield a multitude of products including diepoxides and hydroxy-epoxides (Fig. 16.1-28). 

Eudesmanolides (such as (3)) constitute a large family of natural sesquiterpenoids, with more than 500 members described to date.tl] Their pharmacological properties include antifungal, anti-inflammatory, and antitumor activities among others,[2] but many of them are scarce in nature. To facilitate their chemical synthesis, a novel procedure has recently been developed that provides satisfactory overall yields.[3] Our method is based on the titanocene-catalyzed cyclization of epoxygermacrolides (such as (2)) easily prepared by selective epoxidation of accessible germacrolides such as ( I )-l 1 (5,13-dihydrocostunolidc (1)[4]. 

Analogs were prepared through total chemical synthesis in which the unstable epoxide was replaced with a cyclopropyl group (4). This afforded compounds that were not subject to epoxide metabolizing enzymes, epoxide hydrolase, and glutathione transferase. We called these compounds PBT (PaceBioAcTive compounds). The PBT competed with the native compounds in binding to neutrophil... 

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