Clay M. Sharts

The solubility of oxygen in aqueous fluorocarbon emulsions

Abstract The solubility of oxygen in aqueous fluorocarbon emulsions has been measured directly for several perfluorocarbons and monobromo or monoiodo-perfluorocarbons. The measured oxygen solubilities are consistent with results for the solubility of oxygen in neat liquid perfluorinated organic compounds.

Synthesis of perfluoroalkyl steroids as CO-emulsifying agents for 1-bromoperfluorooctane and other perfluorocompounds

Abstract Syntheses of steroids substituted with perfluoroalkyl groups at C-3, C-7, and C-20 positions on the steroid nucleus are described. Synthetic methods employed included coupling of perfluoroalkylcopper with allylic bromides and Grignard reactions. Free radical additions of perfluoroalkyl iodide to unsaturated steroids and reaction of perfluoroalkyl Grignard reagents with 6-ketosteroid were unsuccessful. Perfluoroalkyl -substituted steroids are desired for testing as co-emulsifying agents in perfluorooctyl bromide/water emulsions which are used as blood substitutes ( synthetic blood ). A rationale for the choice of perfluorooctyl bromide as the oxygen-carrying agent in the fluorocarbon-based blood substitute and on the use of perfluoroalkyl-substituted steroids as co-emulsifying agents is also reported.

Perfluoroalkyl esters of sterols and bile acids

Abstract A series of mono-, bis-, and tris-perfluorooctanoyloxy derivatives of sterols and bile acids were synthesized. To synthesize tris(perfluoro- octanoyloxy) steroids it was necessary to use 4-dimethylaminopyridine (DMAP) as a catalyst. Without DMAP catalyst the hydroxyl group at C-12 remained unreacted. The compounds obtained are intended for testing as co-emulsifying agents for synthetic blood formulations.

Selective fluorination of dispiro[3.1.3.1]decan-5,10-dione by diethylaminosulfurtrifluoride to give 10,10-difluorodispiro[3.1.3.1]decan-5-one and 5,5,10,10-tetrafluorodispiro[3.1.3.1]decane

Abstract Dispiro[3.1.3.1]decan-5,10-dione was selectively difluorinated at room temperature by diethylaminosulfur trifluoride (DAST) to give 10,10-difluorodispiro[3.1.3.1]decan-5-one. The latter was reduced to 5,5-difluorodispiro[3.1.3.1]decane and also reacted with excess DAST to give 5,5,10,10-tetrafluorodispiro[3.1.3.1]decane. Proton and fluorine magnetic resonance studies on 5,5-difluorodispiro[3.1.3.1]decane did not show significant cross-ring coupling (

Perfluoroalkenyl ethers of bile alcohols

Abstract Two synthetic routes are presented for the synthesis of bis- and tris-perfluoroalkenyloxy-substituted bile alcohols with an unsubstituted hydroxyl group in the hydrocarbon side chain. The first route involves selective protection of the 24-hydroxyl group of 3α, 7α, 12α, 24-cholan-tetrol followed by the attachment of 3α, 7α, 12α-hydroxyl groups to the perfluoroalkenyloxy linkages and removal of the protecting group. The second pathway is based on the synthesis of the tris-perfluoroalkenyloxy derivative of 3α, 7α, 12α-trihydroxy-chol-22-ene (or bis-perfluoroalkenyloxy derivative of 3α, 12α-dihydroxy-7-deoxy-chol-22-ene), followed by the hydrobaration of the double bond.

Detection of carbon-fluorine bonds in organofluorine compounds by Raman spectroscopy using a copper-vapor laser

The Raman spectra of fluoro-organic compounds show specific emission bands for carbon-fluorine bonds in the range 500- 800 wave numbers (cm-1)). With very limited exceptions, biological materials do not contain carbon- fluorine bonds. Fluoro-organic compounds introduced into biological samples can be detected by a Raman emission signal. Normal mode C-F bond bands are observed: (1) at 710- 785 cm -1 for trifluoromethyl groups; (2) at 530-610 cm -1 for aromatic organofluorine bonds; (3) a range centered at 690 cm -1 for difluoromethylene groups. Specific examples of normal mode C-F bond emissions for organofluorine compounds containing trifluoromethyl groups are: 1-bromoperfluorooctane, 726 cm -1; perfluorodecanoic acid, 730 cm -1; triperfluoropropylamine, 750 cm -1; 1,3,5-tris- (trifluoromethyl)-benzene, 730 cm -1; Fluoxetine (Prozac) commercial powdered pill at 782 cm -1. Compounds containing aromatic C-F bonds are: hexafluorobenzene, 569 cm MIN1; pentafluoropyridine, 589 cm -1. Difluoromethylene groups: perfluorodecalin, 692 cm-1; perfluorocyclohexane, 691 cm -1. Raman spectra were observed with a standard single monochromator. The 510.8 nm light source was a copper-vapor laser operated at 3-10 watts with 10-12 nanosecond pulses at 10 kHz repetition rate. Detection was made with a time-gated photomultiplier tube. Resonance Raman spectra were also observed at 255.4 nm, using a frequency doubling crystal. Observed spectra were free of fluorescence with very sharp strong C-F lines.

Perfluoroalkenyl ethers of simple sterols

Abstract Base-catalyzed addition of simple sterols to perfluoroalkenes, to give a variety of perfluoroalkenyl steroidal ethers, has been investigated. The outcome of the reaction was dependent on the base used for deprotonation of sterols. With potassium hydride, a mixture of 1- and 2-perfluoroalkenyl steroidal ethers was obtained in a low yield, whereas with n-butyllithium, preferential formation of 1-perfluoroalkenyl steroidal ethers was achieved in high yields.

Synthesis of perfluoroalkyl and perfluoroalkoxy steroids

Abstract Synthetic methods have been investigated to determine the best way to introduce two or more perfluoroalkyl groups (R f = C 6 F 13 -, C 8 F 17 -, or C 10 F 21 -) on the alpha -side of a steroid molecule. Perfluoroalkyl- alpha -substituted steroids are desired for testing as coemulsifying agents in fluorocarbon- based blood substitutes ( synthetic blood ). We postulate that a monolayer of perfluoroalkyl- alpha -substituted steroid will form around a perfluorocarbon micelle and reduce the interfacial tension between the fluorocarbon and the conventionally-used emulsifying agents ( Pluronic F68 or egg-yolk phospholipid), drawn below for Pluronic F68 , a block polymer of polyethylene oxide- polypropylene oxide-polyethylene oxide. Perfluoroalkyl steroids were prepared from potassium salts of steroidal alcohols and perfluoroalk-l-enes. A new esterification procedure for perfluoroalkanoic acids was developed to give tri-perfluoroalkanoic acid esters of methyl cholate (I). Combinations of synthetic methods were used to obtain desired compounds. Free-radical addition of 1-iodoperfluoroalkanes to unsaturated steroids was not useful.

Synthesis of n-perfluorooctyl-substituted steroids

Abstract A series of n-perfluorooctyl-substituted steroids including the examples I–IV illustrated below were synthesized for a study of their physical and biological properties. A variety of synthetic techniques were employed including coupling of perfluorooctylcopper to allylic bromides, Grignard reactions, and opening of an epoxide ring by an alcohol. The full synthetic details for each compound will be presented and the properties of the compounds described; spectral data supporting the structures will be given.