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Alcoholics Anonymous may b e c o m e a thing of t h e past. W i l l i a m Shive, Uni versity of Texas, tells a symposium oni antimetabolites that glutamine seems to work well against alcoholism as untreated alcoholics. Peptic ulcer patients taking glutamine seem to heal more rapidly than ulcer patients on conventional therapy. Antagonism among naturally occur ring amino acids is probably a factor in explaining glutamine's actions, Wil liam Shive told a Symposium on Anti metabolites sponsored by the Division of Biological Chemistry. The research on glutamine -was done b y University of Texas researchers and sponsored b y the Clayton Foundation for Research. • Alcoholism. T h e cause of alcohol ism isn't known, When an alcoholic hasn't h a d alcohol for a long time h e has no compulsion to drink. The first drink seems t o trigger a craving for alcohol. Shive and coworkers thought this efiFect of alcohol might be due to a toxic effect on some biological process. If this were t h e case, a s t u d y of how alcohol inhibits the growth of bacteria could help unravel the mystery. Studies with Streptococcus jaecalts R revealed that ldver extracts reverse the growth-inhibiting action of alcohol, T h e factor in liver extract which causes this reversal h a s been identified as gliztamine. Further studies showed that glutamine-treated rats, when given a choice of water or alcohol, t e n d e d t o choose water. A group of -40 alcoholics w e r e treated with glutamine. E a r l y clinical results showed 20 patients controlled, 1 1 im proved, no change in six, and three a r e worse. Possibly, says Shive, alcoholism i n volves the inhibiting action of alcohol
o n trie production and u s e of glutamine i n biological process. • Ulcers. A factor i n cabbage juice has been reported t o b e effective against ulcers. Shive, while investigat ing this factor, found t h a t cabbage juice contains large amounts of glutamine. Glutamine w a s fed t o 24 ulcer p a tients, who received no other treatment. T h e result: ΙΟ were healed i n t w o weeks, eight in four weeks, and t h e rest within eight weeks. These results w e r e so encouraging t h e study was ex tended to 57 patients, divided into t h r e e groups. One group got gluta m i n e alone. Another group received conventional treatment—antiacid a n d antispasmodic—plus a placebo, while a t h i r d group got conventional treatment plus glutamine. Glutamine alone seemed to do as well or even better than the conventional treatmentIncidence of ulcers i n heavy drink ers is higher than average. Maybe, says Shive, alcohol inhibits the forma tion and u s e of glutamine in t h e bio synthesis of t h e hexosamine part of rnucoproteins. This would prevent t h e formation of enough stomach mucosa and result in a h i g h e r tendency to ulcers. • Viruses Too? W h i l e studying antagonism among naturally occurring amino acids, Shive and coworkers n o ticed that t h e s e chemicals in certain in stances show a beneficial efiFect in pre venting virus infection in mice. High
concentrations of a m i n o acids, such as phenylalanine reduced influenza in fections in mice. A more complete understanding of natural antagonism among amino acids, says Shive, is needed to explain this finding.
Streptomycin Clue Barbiturates raise strepto mycin y i e l d in synthetic fer mentation medium Good yields of streptomycin can b e obtained ACS NATIONAL MEETING from a simple meAgriculturd & ' nutrient dium, according ^Seâ-Cteirnîstiyï to work reported b y Pfizer's H. T. H u a n g to the Division of Agricultural a n d F o o d Chemistry. Since yields in synthetic media a r e normally low, this work m a y provide a useful tool for studying biosynthetic mechanisms. H u a n g finds that streptomycin can be boosted fo-urfold i n a synthetic fermentation m e d i u m by adding 5,5-dialkylbarbituric acids. One of t h e best is t h e hypnotic a n d sedative, Barbital. T h e action of these materials seems to bear no relation t o their hypnotic effect on humans. Streptomycin out-
Scientists in t h e Pfizer biochemical r e s e a r c h method to stimulate streptomycin production media. Examining assay plates for antibiotic mycin fermentations i n flask a r e H . T. H u a n g Davisson
d e p a r t m e n t h a v e developed a with barbiturates in synthetic potency a n d growth of strepto( l e f t ) , Joan Criffin, and J . W.
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put can be increased by compounds that cause hypnosis as well as by those that do not. In fact, one compound that effectively counteracts t h e hypnotic action of barbiturates is good in stimulating streptomycin production. In commercial streptomycin production, t h e medium is usually corn steep liquor or distillers' solubles. These contain complex natural materials that promote high yields; according to one theory, these contain an "activity factor" that stimulates the biosynthesis of streptomycin by acting as precursor or coenzyme. H u a n g believes that the barbiturates, unlike t h e "activity factor," do not act as precursors or coenzymes. They affect only proliferating mycelia during growth in such a way that the over-all enzyme system involved in accumulating streptomycin is increased.
• Molecular Stru«tu re. The action of Barbital depends o n Uv-o structural factors: the barbiturate ring system and the dialkyl substitution at carbon 5. Substitution in t h e ring at a position other than carbon 5-, as in 5,5diethyl-l-methylbarl)itiiric acid, d e stroys activity. On "the other hand, elimination of t h e —CO- *jnit at position 2 to give dietlhylirfcalondiamide does not cause a complete loss of activity. The entire barbiturate ring is replaceable by t h e glutariini-de since t h e activity of ^^-etli^lrnethy^lglutarimide compares favorably with that of 5 methyl-5-ethylbarbituric acid. "It would appear," says Huarag, "that t h e essential feature in^voWed is t h e shape and size of the ring rathter than t h e identity of its member atoms."
Robert B . Woodwcsrd American Chemical Society A w a r d for Creative W o r k in S y n thetic Organic Chemistry ^ sponsored by Hie S y n thetic Organic Chemical Manufacturers ^AssociaRobert B. Woodward (right) gets the award sponsored by Synthetic Organic Chemical Manu- tion facturers Association from A. H. Tenney Using a standard organic reaction as a tool for making a complex natural product is how Robert B . Woodward turned t h e trick in his synthesis of reserpine. And t h e synthesis of reserpine is one of the many reasons why Woodward is t h e first winner of t h e A M E R I C A N CHEMICAL SOCIETY Award for
Creative Work in Synthetic Organic Chemistry, sponsored by the Synthetic Organic Chemical Manufacturers Association. With reserpine, as with other natural molecules, t h e key to successful synthesis is stereospecificity. By starting with t h e Diels-Alder reaction, Woodward and his coresearchers went on t o work out the complicated stereospecificity of reserpine. As h e puts it, the synthesis is a "process of magnification of asymmetry." Actually, any one of his achieve-
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ments in the synthesis o f organic molecules would prof>ably be enough to warrant his receiving the award. A partia] List o f Woodward's successful synthèse-s includes quinine, cortisone a n d other steroids, lysergic acid, strychnine, as well as reserpine. But of almost equal importance, Wood.ward has made it clear to liis fellow chemists that almost no organic molecule whose structure is known i s too complicated for synthe-sis. His work in synthesis lias prompted chemists the world over "to synthesize anything. Born in Boston, WoocHward obtained his Ph.D. from MIT in 1937. Since then, he has been a * Harvard, rising from research assistant t o full professor by 1950. I n 1953, Woodward was named Morris Loeb professor of chemistry a t Ha_rvard.
Long Chains-Good Suds Fourteen-carbon length for d e t e r g e n t molecules found minimum to give stable h a r d - w a t e r foams In addition to syndets, cleaning formulations sometimes contain soaps and fatty acids. These make some syndet foams unstable in t h e presence of calcium ions. But Henry Peper of Lever Brothers finds that detergents composed of straight hydrocarbon chains containing at least 14 carbon atoms give long-lasting suds under these conditions. Peper told t h e Division of Colloid Chemistry that such molecules as sodium tetradecyl sulfate—or the hexadecyl compound—can form mixed films with fatty-acid soaps. This provides stable foams in the presence of divalent metal ions. His film-penetration studies of monolayers at air/water interfaces show strong cohesion in calcium-soap films. This is due to a "tanning" action of Ca^-^ ions, whereby liquid films are transformed into insoluble solid films. These in turn can b e solubilized by detergents having long straight chains which give strong interaction, Peper says. The hydrocarbon portions of some short-chain or branched syndet molecules are "mechanically" unable to provide this interaction, he explains. To demonstrate this, Peper deposits a monolayer of a stéarate or palmitate on the surface of a dilute CaCl 2 solution. He then admits an aqueous detergent mixture into the solution beneath the fatty-acid film. Those detergents which do give stable suds under such conditions are able to penetrate the solid stéarate a n d convert it into a mixed liquid film. Peper has applied this in further work, with Henri L . Rosano, on solidliquid dispersions. Rosano reported that surfactants show greater suspending power than either builders or polyelectrolytes. All three of these detergent components increase the f-potential (electrical surface-charge) on solid carbon particles in distilled water. Calcium ions cause flocculation of carbon black coated with fatty acids; Peper and Rosano attribute this t o cross linking. They find that those detergents which do penetrate Ca-soap films are good dispersing agents for these coated particles.
