Synthesis and some reactions of steroid dimers
The main aims and objectives of this project have been to (i) synthesise pregnane (C21), dinorcholane (C22) and cholane (C24) steroidal monomers as precursors for the synthesis of steroid dimers, (ii) synthesis symmetrical and unsymmetrical steroid dimers via oxalate and simple ester linkages and (iii) perform flash vacuum pyrolysis (FVP) studies on synthesised oxalate steroid dimers in order to generate new steroidal derivatives. The chapter 1 of this thesis reviews the literature since the early part of 1997 on the synthesis of steroid dimers connected directly or via spacer groups in different ring systems as well as side chain through spacer groups. It also reviews the uses of synthetic dimers as molecular umbrellas and their potential applications in drug delivery in the lipid bilayer, and the occurrence of steroid dimers in various natural sources, such as plants and marine organisms, and their biological and pharmacological properties including anticancer activities. The synthesis of pregnane (C21), dinorcholane (C22) and cholane (C24) derivatives by several classical methods has been described in the chapters 2 and 3. The difficulties for the synthesis of C22 amino nitrile using Strecker synthesis and its corresponding acid have been explained. The synthetic routes for several new mixed C18, C21 and C24 anhydrides via oxalate ester formation have also been presented. The chapter 4 depicts the synthesis of several symmetrical oxalate dimers from various natural steroidal hormones such as estrone (C18), testosterone (C19), androstane (C19), pregnenolone (C21), bile acid (C24), cholesterol (C27) and stigmasterol (C29). The importance of the use of pyridine for the formation of oxalate dimers from primary alcohol has been evaluated experimentally. The synthesis of unsymmetrical dimers via side chain and ring A through simple ester linkage has also been presented in this chapter. Flash Vacuum Pyrolysis (FVP) technique and its use for the synthesis of dimers from oxalate dimers have been evaluated. It has been observed that none of the steroid oxalate dimers has produced any new dimers, instead yielded only monomeric olefins. The oximinyl oxalate dimers have been pyrolysed in similar fashion but the reaction has produced some volatile gas and no steroid derivative has been isolated. Interestingly, it has been noted that 5a-derivatives have produced 90% 2-end and 10% 3-ene compounds but 5b-derivatives have yielded solely 3-ene compounds. It has been easy to break 3-oxalate linkages at 600°C but 17-oxalate linkages have needed higher temperature. Possibly this has been because of the steric hindrance at 17-positon.