Susceptibility asymmetry

Only the anion (239) is susceptible to C-alkylation in the 4-position. The two other anions (240) and (241) can only give rise to O-and A-substituted derivatives which result in the asymmetry of Scheme 19. 

Methods used to demonstrate the existence of membrane phospholipid asymmetry, such as chemical labelling and susceptibility to hydrolysis or modification by phospholipases and other enzymes, are rmsuitable for dynamic studies because the rates of chemical and biochemical reactions are of a different order compared to the transmembrane translocahon of the phospholipids. Indirect methods have therefore been developed to measure the translocation rate which are consequent on the loss of membrane phospholipid asymmetry. Thus time scales appropriate to rates of lipid scrambling under resting conditions or when the forces preserving the asymmetric phospholipid distribution are disturbed can be monitored. Generally the methods rely on detecting the appearance of phosphatidylserine on the surface of cells. Methods of demonstrating Upid translocation in mammalian cells has been the subject of a recent review (Bevers etal., 1999). 

Two or more of these conditions can occur at the same time, resulting in asymmetric axial, radial and tangential velocity vectors. Some flowmeters are more sensitive than others to particular types of flow distortion, e.g. orifice meters are affected by pure swirl more than venturi meters are magnetic flowmeters are unaffected by changes in the radial velocity component whereas ultrasonic time-of-flight meters are highly susceptible thereto swirl and asymmetry have the least effect on positive displacement meters and the greatest effect on variable area meters. 

Some materials are very sensitive to disorder [3]. In general, the low-temperature susceptibility follows x a T a (a5=3 0.6 to 0.9). (NMP)(TCNQ) and Qn(TCNQ)2 are examples of this effect, the disorder being intrinsic, attributed to the asymmetry of the cation. (HMTSF)(TNAP) has a similar behavior at low temperature, the disorder being attributed to the TNAP molecule. In (TTT)2I3+6 the disorder results from nonstoichiometry. Similar effects have been obtained when disorder is induced by irradiation... 

Related allylic systems, such as enoates (12) bearing a phosphate leaving group are susceptible to copper-catalyzed Sn2 reactions. Employing copper triflate and a dialkylzinc, peptidic ligand (13) is especially effective at inducing asymmetry at the newly created stereogenic carbon a to the ester in (14) (equation 13). 

Thus, the aldol shown, which is susceptible to Sharpless-type epoxidation, has been obtained from phytal and the protected hydroquinone (ref. 120). Formation of the epoxide presumably with a chiral peracid (or perhaps with a conventional peracid relying on the asymmetry of the substrate) and then cleavage reductively in t-butyl methyl ketone containing lithium aluminium hydride led to a diol. The benzylic hydroxyl group of this was hydrogenolysed to afford the hydroquinone dimethyl ether in 85% yield. Ceric ammonium nitrate (CAN) oxidation afforded the intermediate benzoquinone hydrogenation of which was reported to result in 2R,4 R,8 R-a-tocopherol by, presumably, avoidance of a racemisation step. 

---