Anhydrides nucleophilic ring opening

Our final example is that of cyclic anhydrides, namely prochiral 3-sub-stituted glutaric anhydrides (7.101, R = Me, Et, or Pr). When incubated with lipase in an inert solvent in the presence of an alcohol (methanol, butan-l-ol, etc.), these compounds underwent nucleophilic ring opening with formation of a hemiester (7.102) of (/ -configuration (60-90% ee) [180]. This product enantioselectivity and, of course, the lack of reactivity in the absence of lipase show the enzymatic nature of the reaction. 

Chiral 3-suhstituted glutaric acid monoester (23) can be obtained via Pseudomonasfluorescens lipase-catalyzed nucleophilic ring opening of anhydride (22) hy butanol (38). 

Type II catalytic asymmetric acyl transfer processes have been most extensively developed for the case of ASD of meso-anhydrides by nucleophilic ring-opening with alcohols, and so these processes will be the first type II processes considered here. 

Spivey, A. C. Andrews, B. I. Catalysis of the Asymmetric Desymmetrization of Cyclic Anhydrides by Nucleophilic Ring-Opening with Alcohols, Angew. Chem. Int. Ed. 2001, 40, 3131-3134. 

Nucleophilic ring opening of the cyclic sulfinic-carboxylic anhydride (11) is found to occur exclusively by attack at C=0 <86KFZ843, 88IZV1633>. 

Recently, Langer and co-workers have attached cell adhesion peptide sequence such as RGD onto co-polymers of lactides containing lysine residues (Barrera, 1993). These materials exhibit improved cell interactions in comparison vdth the homopol) mer of lactic acid. They have also s)Tithesized comb polymers containing poly(L lysine) pendant groups (Hrkach, 1995) by the nucleophilic ring opening polymerization of the N-carboxy anhydride of -Z-L-lysine, which was initiated by the -amino terminus of the lysine residue in the co-polymer backbone. 

The enol acetates of aldehydes (but not ketones) are obtained in high yield with acetic anhydride and triethylamine with 4-JV,JV-dimethylaminopyridine. Regiospecific enol acetates (95) are obtained by nucleophilic ring opening of cyclopropyl ketones [equation (60)]. ... 

There are efforts to use the potential of 1. for chemical modification such as conjugation (- isomerism), cyclization with maleic anhydride and epoxi-dation, followed by nucleophilic ring-opening leading to products with functional groups. 

The tetrahedral intermediate is generated by a nucleophilic attack on the carbonyl carbon atom of the activated nucleophile, which in the case of chymotrypsin and trypsin is the catalytic Serl95. The mechanism of chymotrypsin can be compared to that of Song catalyst 77 that catalyzes the nucleophilic ring opening of acid anhydrides. The role of the sulfonamide group is played by the oxyanion hole amide NH groups, and the role of the cinchona alkaloid-derived base is played by the Asp-His-(Ser) dyad/triad. 

Oxidation is the first step for producing molecules with a very wide range of functional groups because oxygenated compounds are precursors to many other products. For example, alcohols may be converted to ethers, esters, alkenes, and, via nucleophilic substitution, to halogenated or amine products. Ketones and aldehydes may be used in condensation reactions to form new C-C double bonds, epoxides may be ring opened to form diols and polymers, and, finally, carboxylic acids are routinely converted to esters, amides, acid chlorides and acid anhydrides. Oxidation reactions are some of the largest scale industrial processes in synthetic chemistry, and the production of alcohols, ketones, aldehydes, epoxides and carboxylic acids is performed on a mammoth scale. For example, world production of ethylene oxide is estimated at 58 million tonnes, 2 million tonnes of adipic acid are made, mainly as a precursor in the synthesis of nylons, and 8 million tonnes of terephthalic acid are produced each year, mainly for the production of polyethylene terephthalate) [1]. 

Even carefully purified acetonitrile and DMF still contain nucleophilic impurities, which can interfer with the electron transfer SEM/OX so strongly that it becomes irreversible and E2 cannot be derived from the polarographic data. With E2 s rather positive, as e.g. in 15, this behaviour is most pronounced. Probably the adduct of 15qx and nucleophiles e. g. 75 undergoes consecutive reactions like ring openings. In these cases addition of some perchloric acid trifluoroacetic acid or its anhydride and aluminium oxide will completely suppress such interfering... 

---