Dimerization cholesterol

Recently dimeric cholesterol-based derivatives were reported as a new class of organogelator architecture. The examples pubhshed so far display a A(LS)2 structure in which a central unit A is sandwiched by two cholesterol moieties. Moreover, all such gemini -type cholesterol-based structures reported to date are based on the cholesterol unit having the natural (S) configuration at C-3. They are listed below according to the main functional characteristics of the central unit. 

The health impairing and toxic elfects of oxidation of lipids are due to loss of vitamins, polyenoic fatty acids, and other nutritionally essential components formation of radicals, hydroperoxides, aldehydes, epoxides, dimers, and polymers and participation of the secondary products in initiation of oxidation of proteins and in the Maillard reaction. Dilferent oxysterols have been shown in vitro and in vivo to have atherogenic, mutagenic, carcinogenic, angiotoxic, and cytotoxic properties, as well as the ability to inhibit cholesterol synthesis (Tai et ah, 1999 Wpsowicz, 2002). 

From activated isoprene, the metabolic pathway leads via dimerization to activated geraniol (1 = 2) and then to activated farnesol = 3). At this point, the pathway divides into two. Further extension of farnesol leads to chains with increasing numbers of isoprene units—e.g., phytol (1 = 4), dolichol (1 = 14-24), and rubber = 700-5000). The other pathway involves a head-to-head linkage between two farnesol residues, giving rise to squalene (1 = 6), which, in turn, is converted to cholesterol (1 = 6) and the other steroids. 

Liposomes were formed from 1,2-dipalmitoylphosphatidylcholine (DPPC) and cholesterol (Choi) and the effect of liposomal entrapment on pulmonary absorption of insulin was related to oligomerization of insulin (Liu et al. 1993). Instillation of both dimeric and hexameric insulin produced equivalent duration of hypoglycemic response. However, the initial response from the hexameric form was slightly slower than that from dimeric insulin, probably due to lower permeability across alveolar epithelium of the hexameric form caused by larger molecular size. The intratracheal administration of liposomal insulin enhanced pulmonary absorption and resulted in an absolute bioavailability of 30.3%. Nevertheless, a similar extent of absorption and hypoglycemic effects was obtained from a physical mixture of insulin and blank liposomes and from liposomal insulin. This suggests a specific interaction of the phospholipid with the surfactant layer or even with the alveolar membrane. 

Chain elongation during polymerization of prenyl units can be terminated in one of a number of ways. The pyrophosphate group may be hydrolyzed to a monophosphate or to a free alcohol. Alternatively, two polyprenyl compounds may join "head to head" to form a symmetric dimer. The C30 terpene squalene, the precursor to cholesterol, arises in this way from two molecules of famesyl diphosphate as does phy-toene, precursor of the Qo carotenoids, from E,E,E geranylgeranyl diphosphate. The phytanyl groups of archaebacterial lipids (p. 385) arise rather directly from geranylgeranyl diphosphate by transfer of the poly-... 

We also investigated chelate binding by dimers of a synthetic hydrophobic macrocycle, in place ofthecyclodextrins [187]. In the systems examined the chelate effect was weaker than that seen with the cyclodextrin dimers. We also studied the strong binding of cholesterol by some cyclodextrin dimers and a cyclodextrin polymer, and saw that the large sterol could occupy parts of two binding cavities [188]. 

In summary, the dimeric lipids (29a-29h) with low m-value (3-4) and high m-value (20-22) showed exceptional thermal, lipid-packing and cholesterol-association properties. Obviously the introduction of a polymethylene spacer chain at the level of headgroup brought about dramatic effect on the aggregation behavior, membrane organization and lipid packing of 29. 

It is iot obvious how the two farnesyl pyrophospate molecules could be combined to make the steroid skeleton, and the chemistry involved is extraordinary and very interesting. The first clues came from the discovery of the intermediates squalene and lanosterol. Squalene is obviously the farnesyl pyrophosphate dimer we have been looking for while lanosterol looks like cholesterol but still has all 30 carbon atoms. 

Oxidation and Dehydrogenation.—Some novel oxidations of A -olefinic steroids are reported. Silver oxide, in refluxing benzene or toluene, converted cholesterol into the 6,6 -dimeric compound (148), probably through a one-electron process. The dimer decomposed above its m.p. to give an equimolar... 

Cholesterol, on reaction with dibenzoyl peroxide followed by trichloroacetic acid, gave a blue colour attributed to cations with conjugated unsaturated structures. Cholesta-2,4,6-triene and 3-(cholest-5-en-3/8-yl)cholesta-2,4,6-triene were isolated from the product mixture. Some other sterols gave diverse colours.The coloured solutions formed from cholesterol or oestrone with antimony trichloride give e.s.r. spectra suggesting the presence of radical-cations. Cholesta-3,5-diene and 3,3 -bicholesta-2,4-diene were isolated from the reaction of cholesterol, and the hexaene (131) from oestrone. Dimeric and trimeric products have been... 

---