Silicon-containing steroids

Other, removable cation-stabilizing auxiliaries have been investigated for polyene cyclizations. For example, a sdyl-assisted carbocation cyclization has been used in an efficient total synthesis of lanosterol. The key step, treatment of (257) with methyl aluminum chloride in methylene chloride at —78° C, followed by acylation and chromatographic separation, affords (258) in 55% yield (two steps). When this cyclization was attempted on similar compounds that did not contain the C7P-silicon substituent, no tetracycHc products were observed. Steroid (258) is converted to lanosterol (77) in three additional chemical steps (225). 

DNPH-steroids can be separated by HPLC with several partition systems [31,32] including 1 % /3,/3 -oxydipropionitrile (BOP) on Zipax with eluting solvents containing 0-20% tetrahydrofuran in heptane or 2-methylheptane, or 1% ethylene glycol on Zipax with 3% chloroform in heptane as the mobile phase. Reversed-phase chromatography with 1.0% hydrocarbon polymer (HCP) or 1% cyanoethyl silicone (ANH) on Zipax and methanol-water as the mobile phase can be useful for the separation of several polar steroids. Gradient elution (water to methanol) on octadecylsilane (ODS), Permaphase (chemically bonded on Zipax), also provides a separation of polar DNPH-steroids. The separation of five DNPH-steroids on 1.5% BOP coated on Zipax is shown in Fig.4.13. 

As an example of a clear improvement in separation we can cite the data on the retention of steroids on a non-polar silicone stationary phase, SE-30, as presented by Heftmann [54]. Two monohydroxy-steroids, 5a-cholestan-3 3-ol and 5-cholesten-3 3-ol, have the same relative retention (2.85) on a column containing a non-polar stationary phase (internal standard cholestane), but the relative retentions of their trimethylsilyl derivatives are 2.60 and 2.55 and those of their chlorodichloroacetates are 3.79 and 3.62, respectively. The relative retention times of 3a-hydroxy-5a-androstan-17-one and 3j3-hydroxy-5a-androstan-17-one are similar at 0.96 and 1.00, respectively, whereas those of their TMS ethers are 0.46 and 0.61, respectively. 

Haleblian J, Runkel R, Mueller N, Christopherson J, Ng K. Steroid release from silicone elastomer containing excess drug in suspension. Journal of Pharmaceutical Sciences. April 1971 60(4) 541-545. PubMed PMID 4108479. 

Another major breakthrough in lead design is the steroid-eluting electrode (Figure 11.12). About 1 mg of a corticosteroid (dexamethasone sodium phosphate) is contained in a silicone core that is surrounded by the electrode material. The leaking of the steroid into the myocardium occurs slowly over several years and reduces the inflammation that results from the lead placement. It also retards the growth of the fibrous sack that forms around the electrode, which separates it from viable myocardium. As a result, the dramatic rise in acute thresholds that is seen with nonsteroid leads during the 8-16 weeks postimplant is nearly ehminated. 

May contain volatile and non-volatile steroids, synthetic musks, lipids and silicon compounds... 

A third type of silicone implant fabrication is a hybrid of the capsule and matrix-type implants such as microsealed drug delivery system." This system consists of a matrix-type silicone im.plant with microsealed compartments containing drug/steroid dissolved or suspended in a hydrophilic solvent. Addition of solvents in the silicone implants changes the physical structure of the silicone network and affects the solubility and diffusivity of drugs/hormones so that release fluxes of drugs/hormones increase."... 

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