AL» meeting briefs Wood preservatives catch ride on supercritical C 0 2 Supercritical carbon dioxide works well to carry preservatives into plywood and other wood-based composites, according to John Simonsen of the department of forest products at Oregon State University. Supercritical fluids have been used commercially to extract materials, including caffeine from coffee beans, but there are no commercial systems using them to deliver materials into porous media, Simonsen says. Supercritical C0 2 dissolves biocides almost as well as a liquid would, and penetrates both the wood and glue layers of the composite like a gas. By lowering the temperature and pressure after penetration, the biocide is deposited in the wood. Treatments of 30 to 60 minutes were effective on virtually all types of panels and wood samples tested. The pressure used (from 1,800 to 4,500 psi) didn't cause deformation, according to Simonsen. Further development work will evaluate the field performance of the panels and explore fluid recycling.^
HIV protease inhibitors built on carbohydrate scaffold A new class of drug candidates that inhibit the protease enzyme of the human immunodeficiency virus are under development at Gilead Sciences, Foster City, Calif. The candidates are based on small carbohydrate scaffolds, with the same symmetry as HIV protease, that are modified with various side chains. The scaffold provides a relatively small, nonpeptide hydrophilic core, features that may make the compounds effective when taken orally, according to Gilead Sciences' Lawrence R. McGee. The research is a collaboration between Gilead scientists and researchers at the National Cancer Institute's Frederick Cancer R&D Center in Maryland. One candidate drug has a scaffold derived from mannitol that has a seven-membered ring containing a sulfur atom. Double oxidation of the sulfur atom extends the hydrophilic core, thereby improving potency and reducing the size of the compound. Several compounds, including one with a molecular 42 SEPTEMBER 16, 1996 C&EN
weight of less than 600, are potent inhibitors of HIV protease in animal tests, McGee said. One showed good absorption when given orally to dogs and remained at effective levels in the blood plasma for more than 12 hours. Gilead has several of these molecules in preclinical and toxicology tests; none have been tested yet in humans.^
Mechanism of soap browning uncovered Chemists at Japanese cosmetics giant Shiseido in Yokohama report why triethanolamine (TEA) soaps turn brown on storage in warm environments. Makers of personal care products favor such soaps as triethanolammonium laurate for their quick foaming, dense lather, and good low-temperature solubility. But the down side for cosmetics is the gradual color change. A professional perfumer at Shiseido tipped off researchers Hiroyuki Yano, Akira Noda, Tadao Hukuhara, and Kiyoshi Miyazawa that samples in accelerated aging tests at 120 °F smelled faintly of aldehyde and amine. The Yokohama team followed up that tip with studies that show that TEA decomposes to ethanolamine and 2 mol of acetaldehyde. Acetaldehyde then condenses to form crotonaldehyde. Crotonaldehyde forms a Schiff base with the ethanolamine. And finally, the unsaturated Schiff base undergoes 1,4-polymerization to colored products.^
Iridium converts strained olefins into adhesives A versatile reaction catalyzed by iridium easily converts strained cyclic olefins such as norbornenes to rubberlike polymers that can be used as adhesives. The reaction was developed by chemist Katherine A. Brown and coworkers at 3M, St. Paul, Minn. Under various conditions, low levels of iridium-based catalysts such as [Ir(cyclooctadiene)Cl]2 produce quantitative yields of high molecular weight (greater than 1 million) polymers. The iridium catalysts are robust—active over a wide temperature range (0 to more than 100 °C) and tolerant of additives. The reactions proceed more rapidly in air than in an inert atmosphere, an advantage for batch reactions and in-line processing. An example of a
typical formulation includes the monomer 5-hexyl-2-norbornene, tackifiers, the catalyst, and the cocatalyst Zn[N(S02CF3)2]2 at a ratio of 345:260:1:1.4 by weight. The formulation is coatable for hours at room temperature. When the mixture is applied to a polyester backing at a thickness of 75 Mm, polymerization is complete within two minutes at 116 °C to give a pressure-sensitive adhesive.^
Inexpensive hydride reducing agent Chemists at the University of Manchester Institute of Science & Technology in England find that poly(methylhydrosiloxane) (PMHS) with catalytic amounts of tetrabutylammonium fluoride reduces ketones, carboxylic acids, and esters to alcohols in 80 to 95% yields. Mark D. Drew and Nicholas J. Lawrence note that PMHS is inexpensive, stable to air and water, nontoxic, and soluble in most organic solvents. The immediate product is a silyl ether of the alcohol, which may be left on as protecting group for a next step or removed in a mild acidic, basic, or neutral work-up. PMHS, plus a catalyst made from titanium(rV) isopropoxide and enantiomeric iraras-l,2-diaminocyclohexane, reduces acetophenone to oc-phenethyl alcohol in 97% yield but only 26% enantiomeric excess. That suggests a search for a better ligand may result in an industrially attractive enantioselective reduction.^
Approach yields protected amino acids Researchers at Affymax, a combinatorial chemistry drug development firm in Santa Clara, Calif., have devised a synthesis of 9-fluorenylmethoxycarbonyl (FMOC) derivatives of amino acids under neutral conditions in the absence of water. The method may be useful to make FMOCprotected derivatives that form gels in water. Stephen P. Raillard, Adam D. Mann, and Ted A. Baer first treat the amino acid with A^-methyl-A^-trimethylsilyltrifluoroacetamide in methylene chloride to get the trimethylsilyl ester of the amino acid. Then to the same vessel they add 9-fluorenylmethoxycarbonyloxysuccinimide, which results in the FMOC derivative of the amino acid trimethylsilyl ester. A methanol work-up cleaves the trimethylsilyl ester. Yields are almost
quantitative. There is no detectable racemization or formation of FMOC-dipeptide impurities.^
Tritioacetylating reagent labels biological molecules Scientists in California have developed a new reagent to tritioacetylate pep tides and other biologically important molecules. Such reagents are needed to radioactively mark many compounds so that their various characteristics and properties can be detected and ana lyzed. The new compound, A^-tritioacetoxyphthalimide, has several advantag es over standard reagents such as tritiated acetic acid and acetic anhydride, says Manouchehr Saljoughian, a chem ist with the Na tional Tritium Ο Q Labeling Facili- ^^γ^\ il ty at Lawrence [Ι Γ Ν—Ο CH2T Berkeley Na- ^ ^ " " " ^ tional Laborato° ry (LBNL). Both substances suffer from low tritium con tent, volatility, and poor chemical selec tivity. Saljoughian and colleagues at LBNL created the new reagent, which readily tritiates α-amino and sulfhydryl groups in proteins. Akritioacetoxyphthalimide, which the authors say is quite easy to prepare, is stable and also appears to be active in dimethylsulfoxide, methanol, dioxane, and water.^
Amines, thiols modify diamond surfaces Changing the chemistry of diamond by functionalizing its surface could improve diamond's adhesion to metals. It also can be used to tune diamond's electronic properties. Duncan W. Brown, a chemist at Advanced Technology Materials Inc., Danbury, Conn., and John B. Miller, now an assistant professor at Western Michi gan University, Kalamazoo, have pre pared amine- and thiol-terminated dia mond surfaces. They find that surface primary amines enhance diamond's ad hesion to metals such as gold. In addi tion, surface modification alters electrical properties such as specific contact resis tance and surface sheet resistance. It also changes the ease by which electrons can be extracted from the surface—a proper ty called electron work function. Brown
and Miller prepared the modified surfaces from a hydrogen-terminated diamond sur face similar to that of natural or synthetic diamond single crystals and polycrystalline films grown by chemical vapor deposition. They chlorinated the surface either by heating or by ultraviolet (UV) irradiation in chlorine gas. UV irradiation of the result ing chlorinated diamond in gaseous am monia, methylamine, or hydrogen sul fide produced surfaces functionalized with a primary amine, a secondary amine, and a thiol group, respectively. Brown says chlorinated diamond is a necessary intermediate to amine and thiol-terminated surfaces.^
Protein cross-linking by glutaraldehyde Researchers at Japan's National Institute of Materials & Chemical Research sug gest a mechanism for the cross-linking of protein chains by glutaraldehyde, which has wide use as a polypeptide fixative. Studies by Jun-ichi Kawahara, Keiichiro Ishikawa, Tadafumi Uchimaru, and Haruo Takaya indicate that the cross-linked structure is not simply a double Schiff base of monomolecular glutaraldehyde with two pendant e-amino groups of ly sine molecules. Instead, after glutaralde hyde forms a Schiff base imine with one such amino group, it undergoes an aldol condensation with other glutaraldehyde molecules. The final structure is a linear aldol-condensed oligomer of glutaralde hyde molecules of indefinite length, with amino groups of lysine units from sever al peptide chains branching off that.^
Polymeric resin replaces solvent in 'green' synthesis Investigators at Massachusetts Institute of Technology have made a polystyrene res in bearing tetrahydrofuran (THF) side chains that can replace THF as solvent in environmentally friendly organic synthe sis. Water-soluble THF is hard to recover in industry. Graduate student Linda K. Molnar, organic chemistry professor Ste phen L. Buchwald, and chemical engi neering professor T. Alan Hatton dissolve the resin in heptane-toluene and use that mixture as a solvent to carry out an alkylation that usually goes best in THF. Hep tane-toluene may be environmentally ac ceptable under certain circumstances;
for example, if the mixture is to be used in the next step of a multistep sequence or as a recrystallization solvent. The MIT researchers make the THF-functionalized resin by treating m-chloromethylstyrene with tetrahydrofurfuryl alcohol to get m-tetrahydrofurfuryloxymethylstyrene. They polymerize this monomer to a res in that has pendant THF groups.^
Trimethylsilyl cyanide affords N-substituted formamides Medicinal chemists at the Parke-Davis Di vision of Warner Lambert Co., Ann Ar bor, Mich., find that trimethylsilyl cya nide is a novel reagent for the Ritter reaction—the sulfuric-acid-mediated re action of nitriles with alcohols to make amides. Huai G. Chen, Om P. Goel, Ste phen J. Kesten, and James A. Knobelsdorf find that their version of the reac tion is superior in converting a piperidin4-ol to a 4-formaminopiperidine as a key drug intermediate. Exploring further, they find that benzylic and tertiary alco hols give better yields than secondaries. For example, benzilic acid gives 95% of diphenylformaminoacetic acid, 1-adamantanol gives 78% of N-formyl-l-adamantylamine, and 2-phenylethanol and 3-phenyl-l-propanol do not r e a c t s
Thermosensitive gels squeeze out drugs A new drug delivery system relies on hydrogels that swell and shrink depend ing on the temperature of their environ ment, according to Anna Gutowska, a postdoctoral fellow at Pacific North west National Laboratory, Richland, Wash. She and Sung Wan Kim of the University of Utah's Department of Pharmaceutics & Pharmaceutical Chem istry placed thermosensitive crosslinked poly(7V-isopropylacrylamide) hydrogel and a solution of acetaminophen inside a rigid capsule with two very small holes. At 35 °C, the gel absorbs water and expands, plugging the holes. At 40 °C, however, the gel expels water and shrinks, opening the holes and al lowing some of the drug solution to dif fuse out of the capsule. This rapid re sponse within the range of physiologi cal temperatures makes the device a good candidate for delivering drugs that reduce fever, the researchers say.^ SEPTEMBER 16, 1996 C&EN 4 3
