Paul B. Savage and Dr. David B. McMullin, Chemistry and Biochemistry
The stability of all cellular life in the presence of adverse environmental conditions may be attributed to the function of cellular membranes. Membranes are unique in their ability to act as barriers with selective permeability (1). Such selective permeability allows cells to control and differentiate between the chemical constituents of their intracellular fluid and that of their extracellular environment.
While such a barrier system is essential to cellular life, the membrane bilayer has posed many challenges for researchers. Many therapeutic compounds are hydrophilic, and thus are blocked from cellular entry. Research has attempted to overcome this problem by specifically designing amphiphiles to aid in the diffusion of hydrophilic compounds through the membrane bilayers (2).
In this research cholic acid has been used to synthesize a special amphiphilic molecule (called compound 5), which may subsequently be used to form a target dimer. The target dimer is expected to be able to nondestructively penetrate membrane bilayers.
Compound 5 was made in order to probe various oxidation conditions. Scheme 1 illustrates how Compound 5 has been synthesized in a purifiable form. (Compound 1 in Scheme 1 was prepared as described by Li and coworkers) (1).
Scheme 1 utilizes an oxidation via Jones Reagent and sonication. Allanson and coworkers have previously reported the use of these conditions to oxidize numerous delicate compounds (2).
Having synthesized Compound 5, a two part synthetic pathway has been devised for the synthesis of the target dimer. This pathway consists of making an adequate amount of starting material similar to Compound 5. This starting material is subsequently linked together to form the target dimer. This synthetic pathway is currently being researched.
References
- Stryer, L. Biochemistry, 4th ed.; W.H. Freeman and Company: New York, 1995; p 263.
- Janout and co-workers used cholic acids to design “molecular umbrellas” to open and close around hydrophilic therapeutic compounds. Janout, V.; Lanier, M.; Regen, S. L. J. Am. Chem. Soc. 1997, 119, 640.
- Li, C.; Peters, A. S.; Meredith, E. L.; Allman, G. W.; Savage, P. B. J. Am. Chem. Soc. 1998, 120, 2961.
- Allanson, N. M.; Liu, D.; Chi, F.; Jain, R. K.; Chen, A.; Ghosh, M.; Hong, L.; Sofla, M. J. Tetrahedron Lett. 1998, 39, 1889.