Oximes, immobilization

Domino radical transformations on solid support can also be used, as shown by Naito and coworkers [18]. Thus, immobilized oxime ether 10-55 (Wang resin) afforded the tetrahydrofuranones 10-57 after removal of the resin, when it was exposed to BEt3 in the presence of different alkyl iodides 10-56 (Scheme 10.14). 

Immobilized, highly reactive phenyl esters can be prepared by acylating resin-bound 4-acyl-2-nitrophenol (Entry 4, Table 3.13 [285-288]) or 4-(aminocarbonyl)-2,3,5,6-tetrafluorophenol (Entries 7 and 8, Table 3.13). These esters are similar to oxime esters (see Section 3.3.3.3), and even react with weak nucleophiles such as anilines or alcohols. This type of linker is not, therefore, well suited for long synthetic sequences on insoluble supports, but only for the preparation of simple acid derivatives. Because cleavage yields the unchanged phenol, these resins can be reused several times, which renders this strategy of preparing acid derivatives quite cost-effective. 

This first section wiU study different regjoselective processes of several types of nucleosides depending on the lipase used. Application of biotransformations over these compounds has acquired great importance in order to prepare new derivatives with interesting pharmacological activities. Two lipases, namely, Candida antarctica type B (CALB) and Pseudomonas cepacea, free (PSL) or Pseudomonas cepacea, immobilized (PSLC), are selective towards one of the two hydroxyl groups of different 2 -deoxynucleosides. Thus, it is possible to prepare the acylated compounds in S -position with CALB [10], whereas PSL is selective towards the secondary hydroxyl group [11]. Vinyl or oxime esters can be used as acyl donors. 

The authors also investigated the feasibility of a radical cyclization-capture sequence [14] using immobilized phenylsulfonyl oxime ether 107 and iodide 110 (Scheme 23). Upon treatment with hexamethylditin, 110 undergoes a sequence of two 5-exo cyclizations followed by capture of the resultant radical by resin 107. Cleavage from the support gave 111 in moderate yield. 

Wu P, Brand L. N-terminal modification of proteins for fluorescence measurements. Methods Enzymol. 1997 278 321-330. Gilmore JM, Scheck RA, Esser-Kahn AP, Joshi NS, Erancis MB. N-terminal protein modification through a biomimetic transamination reaction. Angew. Chem. Int. Ed. 2006 45 5307-5311. Christman KL, Broyer RM, Tolstyka ZP, Maynard HD. Site-specific protein immobilization through N-terminal oxime linkages. J. Mater. Chem. 2007 17 2021-2027. 

Another field of application for active esters is solid-phase synthesis. Some polymer-supported reagents are available commercially (see Fig. 9). The acid is first immobilized on a polymer support as an active ester and the excess reagents are washed away conveniently. Finally, the amide is released by amine treatment. During the cleavage, a limited amount of amine can be used to avoid the presence of excess amine in the final mixture. The acid is loaded onto the resin using classic ester condensation methods for TFP resin 35 (66), HOBt resin 36 (67), and oxime resin 37 (68). In the case of the triazine resin 38, the acid is loaded via an aromatic nucleophilic substitution in the presence of a base (69). 

Regioselective acylations of polyhydroxylated compounds such as carbohydrates, glycerols, steroids, or alkaloids have been carried out with lipases, esterases, and proteases [13, 20]. One example is the Candida antartica lipase (immobilized on acrylic resin) catalyzed monoacylation of the signalling steroid ectysone (1) giving selectively the 2-C)-acetate 2 (eq. (1)). Using vinyl acetate for this transesterification the reaction was irreversibly pushed to the product side, since the liberated enol instantaneously isomerizes to acetaldehyde [21]. The sometimes unfavorable aldehyde is avoided when 1-ethoxyvinyl acetates [22], trichloro- or -fluoroethyl esters [23 a, b], oxime esters [23 c] or thioesters [23 d] are employed for the quasi-irreversible reaction courses. 

Under the usual conditions for enzyme-catalyzed (trans)esterification, the composition at equilibrium is often far from optimal. Complete conversion can be achieved by removal of alcohol and/or water by vacuum or chemical means, i.e. by the use of enol or oxime" esters. We endeavoured to fix the water activity at a low level by adding zeolite to the reaction mixture. Immobilized enzymes which are stable in these very dry media have recently become available. ... 

Eshghi and Hassankhani (2007) studied the Beckmann rearrangement using sulfuric acid immobilized on the surface of silica gel (Scheme 5.57). Under these conditions, high conversion and excellent selectivity were found in the Beckmann rearrangement of cyclohexanone oxime. Treatment of carbamates and oxazolidi-nones with anhydrides in the presence of SSA under solvent-free conditions at room temperature results in the formation of V-acyl carbamates and oxazolidinones... 

An idenhcal approach was followed for the preparahon of combinatorial libraries from ursohc acid, betulinic add, and lupeol (Figure 11.50). In the case of betuhnic acid (105) and ursohc acid, the triterpene scaffold was immobilized onto a prederivatized amino acid on 2-chlorotrityl or Sieber amide resin, and treated with a variety of ahphahc, aromatic, and amino acids, to generate a library of C-3 and C-28 derivatives 106.In another series, C-3 oxime esters 107 were prepared from... 

Oxime Aminooxy and aldehyde/ketone pH 6—8, reaction time <30 min No catalyst required Cell encapsulation, protein immobilization ... 

The Naito laboratory has investigated the applicability of radical reactions in solid-supported chemistry. A pronounced effect of the solid support on the stereochemical outcome of a radical reaction was reported for the addition of an alkyl radical onto the chiral oxime 139, delivering a-amino acid derivatives 140 in good yield and with high stereoselectivity (Scheme 6.32). Higher diastereoselectivities were observed with the substrate 139 immobilized on the solid support (>90% de), compared to comparable solution-phase reactions of 139 (72-85% de). This effect was rationalized based on the lower reactivity and reduced reaction rate of the immobilized oxime, inducing an enhanced selectivity. ... 

To increase the OP/enz5mie stoichiometry, polyurethane-immobilized enzymes were combined with oximes (enzyme reactivators such as HI-6 Peter et al., 2007) so that the catalytic activity of OP-inhibited AChE (or BChE) is rapidly and continuously restored before irreversible aging of the enzyme-OP complex can occur. Thus, the OP is continuously detoxified. A reusable immobilized-enzyme sponge of ChEs and oximes for OP decontamination is the envisioned product. Next, it... 

---