Esters positions

In a related approach, Padovani et al. prepared copolymers of styrene and a styrene derivative containing two pendant ester bonds using free-radical polymerization (Scheme 15) [108], Transesterification reactions were conducted with Novozym 435 as the catalyst and benzyl alcohol or (rac)-l-phenylethanol as the nucleophile. Interestingly, the ester bond closest to the polymer backbone (position A in Scheme 15) remained unaffected, whereas ester bond B reacted in up to 98% to the corresponding benzyl ester. The transesterification was not only highly chemoselective but also enantioselective. Conversion of (rac)-l-phenylethanol in the transesterification reaction amounted to a maximum conversion of 47.9% of the (/ )-alcohol, and only at the ester position B. 

If one or more of the ester positions is held by an R group, the compound will be resistentto detoxification and make a more stable derivative of Achase. 

The remainder of the radioactivity is associated with three main phospholipid classes, namely, phosphatidylcholine, phosphatidylethanolamine, and the phosphoinositides, mainly PIP2. Nonetheless, this type of result is commonly attributed to the action of a phospholipase A2, which is activated upon agonist interaction with the platelet. The other presumed product, a lysolecithin, would not be labeled in the above experimental protocol and thus, due to the very small amount formed in the reaction, could not be detected. Though one could potentially label the polar head group of the parent phosphoglycerides, there is little need to do so since the arachidonic acid is associated almost exclusively with the sn-2 ester position on phosphoglycerides. Consequently, the release of free arachidonic acid can be safely attributed to phospholipase A2 activity. While the yield of arachidonic acid is very low, the activation of the cell occurs only over a short time span, anywhere from 5 sec to 1 min. Thus self-control of cell activation is evident. 

In the biochemical method, the enzyme phospholipase A2, isolated from Naja naja snake venom can attack the native alkenylacylglycerophosphocho-line and liberate completely the esterified fatty acid and the alkenyl(lyso)glyc-erophosphocholine. On the basis of the stereospecific mode of attack of this enzyme on the 2-acyl ester position of sn-3 phosphoglycerides, it can be concluded that the naturally occurring alkenylacylglycerophosphocholine possessed the sn-3 stereochemical configuration. 

Assuming that the above enzymatic reaction was run in an ether-rich medium, the products can be isolated by thin-layer chromatography. Thus, the fatty acids released from the sn-2 position can be easily recovered as well as the lysophosphatidylethanolamine. The latter derivative will contain the fatty acyl groups associated with the sn-1 ester position. Base-catalyzed metha-nolysis of the lyso compound will produce the methyl esters. In the usual instance, these will contain mainly saturated chains. In any event the attack by phospholipase A2 can proceed smoothly to completion. These results would strongly support an sn-3 stereochemical configuration for the parent diacylphosphatidy lethanolamine. 

Lipases can be divided into those that have a positional specificity and those that do not. The former preferentially hydrolyze the ester bonds of the primary ester positions. This results in the formation of mono- and diglycerides, as represented by the following reaction ... 

It is well known that synthetic arginine esters, such as NQ -tosyl-L-arginine methyl ester (TAME), are hydrolyzed by thrombin and inhibit the clotting activity of thrombin. Since the binding specificities of arginine derivatives would be determined by the structure of both sides of arginine, i.e., amino as well as carboxyhc sides, a series of studies were undertaken by Okamoto et al. [104-106] to obtain potent and specific inhibitors of thrombin by modifications of the Na-substituent and methyl ester positions of TAME. 

Figure 12. Histochemistry of cholesterol ester in mouse liver treated with 3-H-CPIA-cholesterol (X72O) 5 weeks after single intravenous injection of ca- 30 mg/kg of 3-H-[2R]-CPIA-cholesterol ester. Positive coloring (arrows) is observed in giant cells.

Treatment of 3,4-didehydro-L-pyroglutamate, protected as a cyclic orthoester, with ESTA gave a mixture of two diastereomeric products that differed in configuration at the a-ethyl ester position (eq 11). These diastereomers could be separated and converted to enantiomeiically pure, cyclopropane L-glutamate analogs, ... 

Acquotti, D., Fronza, G., Riboni, L., Sonnino, S., and Tettamanti, G., 1987, Ganglioside lactones H-NMR determination of the inner ester position of GDlb-ganglioside lactone naturally occurring in human brain or produced by chemical synthesis, Glycoconjugate J. 4 119-127. 

Maleate esters of APG are intermediates in the preparation of sulfosuccinate APG esters. Positive ion spectra show unreacted APG, as discussed above, and [M -I- Na]" and [M + NH4]" ions of the esters up to a degree of APG polymerization of 3. [2M -I- Na]" and [2M + NH4] ions are also visible, where M represents mono- or dimaleates of APG with varying alkyl chain lengths and with degree of APG polymerization up to 3. [M -I- H]" ions... 

---