Short Synthesis Leads to Alkaloids Simple dialdehyde yields complex compound resembling strychnine and curare alkaloids A simple indole derivative yields in one operation a complex organic com pound containing five fused rings and six asymmetric centers, University of Wisconsin chemists report. And the structure of this compound closely re sembles the structures of strychnine and the curare alkaloids. The relatively simple synthesis sim ulates the supposed path by which plants make such alkaloids. The dis covery may open the door to synthe sizing complex natural products along short, efficient routes, say Dr. Ε. Ε. van Tamelen, Dr. Lloyd Dolby, and Rich ard Lawton. With minor changes in the structure of the materials in the model system, the scheme should per mit synthesis of any of several alka loids, Dr. van Tamelen adds. Most
immediate commercial prospect for the synthesis appears to be the curare alka loids, now useful in medicine as anti spasmodics. Simple Reaction. The beauty of the whole reaction is its simplicity, says Dr. van Tamelen. Periodate cleavage of the diolamide, Ν-(β-ιηdoleacetyl ) -4- ( r-amino-2' - butyl ) - cyclopentan-l,2-diol, produces the key intermediate in the scheme—N-( β-indoleacetyl) -β'- ( l-amino-2-butyl ) - glu tardialdehyde. This cyclizes sponta neously to an alkanolamide. Subse quent heating in an aqueous acid sys tem such as acetic acid-sodium ace tate or formic acid-sodium formate yields—probably via an indolinene— the five-ringed fused system whose structure corresponds to a tertiary base
of oxotetrahydro-C-fluorocurarine, one of the curare alkaloids. One major advantage: There's no need to isolate each of the relatively unstable intermediates involved in going from the dialdehyde to the alka loid. The sequence does pose a puzzle, though. Normally, the alkanolamide would be expected to undergo a-cyclization to a true indole derivative, instead of yielding a five-ring sys tem. Dr. van Tamelen's group is now seeking the reasons for this unexpected result. Early Steps. The route to the diol amide starting material begins with alkylation of ethylcyanoacetic ester with the p-toluenesulfonate of A3-cyclopentenol. The resulting product— when saponified and decarboxylated— gives 2- ( A3-cyclopentenyl ) -butyronitrile. Lithium aluminum hydride re duces this nitrile to the unsaturated primary amine, 2-(A 3 -cyclopentenyl)n-butylamine. This is heated with methyl indole-3-acetate to get the oily unsaturated amide, N-(/?-indoleactyl)4- ( r-amino-2'-butyl ) -cyclopentene - 1 .
New Synthesis Approaches Biogenetic Routes
Tertiary Base of OxotetrahydroC-fluorocurarine
Indole Cyclization Product Spontaneous
Mkanolamide Normal
Heat + Acetic Acid — Sodium Acetate
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BRIEFS phosphorus sulfides sulfuryl chloride muriatic acid tions it may be used for the chlorination and sulfonation of both aliphatic and aromatic derivatives. It may also be ap plied as an acylating and condensing agent. The simplicity of these reactions, their ease of control and their high yields promise to make the reagent par ticularly useful in many applications which require simple and unspecialized equipment." What was said in 1944 is just as true today. For a reprint of this comprehen sive technical article and our technical data sheet, check coupon below*.
BETTER ABSORPTION WITH HCL
HOOKER OFFERS TWO OF THE FOUR According to the Encyclopedia of Chemical Technology, only four of the 14 phosphorus-sulfur compositions are true chemical entities. We offer two of them: phosphorus sesquisulfide (P4S3) and phosphorus pentasulfide (P2S5). Both have wide use as reagents in or ganic synthesis. We provide the penta sulfide as a grey-yellow material fused solid or as a powder in three mesh sizes. It has a typical melting point of 278 °C. Our phosphorus sesquisulfide is a lem on-yellow powder with a typical melt ing point of 171 °C. It contains no free phosphorus. Write for complete data sheets on both.
WHAT THEY SAID IN 1944 A technical paper in the September, 1944 issue of Industrial and Engineer ing Chemistry predicted great things for a relative newcomer on the reagent scene, Hooker sulfuryl chloride. It said : "Sulfuryl chloride is a versatile re agent with great potentialities in organ ic synthesis. Under appropriate condi-
Now they're activating clay with mu riatic acid instead of the cheaper sul furic acid. Reason : 25% to 75% higher decolorizing efficiency of the resulting clays. Chloride salts produced in the digestion step are more soluble than sulfites produced by H2SO4. The new process is a boon to lube oil producers, vegetable oil refiners and manufactur ers of catalysts. Our authority for this is Chemical Engineering, January 12, 1959, page 62. Since Hooker is a major producer of muriatic acid, we look with great fa vor on any new process that involves substantial tonnages of this product. We produce two grades, commercial and Hooker white, both arsenic-free and of exceptional purity. Our data sheet No. 720-Β will be sent on request.
For more information, check here and mail with name, title and company address: Π Phosphorus pentasulfide, data sheet Π Phosphorus sesquisulfide, data sheet Π Muriatic acid, data sheet Π Sulfuryl chloride, reprint and data sheet
HOOKER CHEMICAL C O R P O R A T I O N 608-1 Forty-seventh Street, Niagara Falls, New York Sales Offices: Buffalo Chicago Detroit Los Angeles New York Niagara Falls Philadelphia Tacoma Worcester, Mass. In Canada: Hooker Chemicals Limited, North Vancouver, B. C.
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Chemical and Lubrication Engineers Outstanding Career Openings at Boeing Boeing's Transport Division has immediate openings for experienced men to work as members of the Structures Staff in research into aircraft applications of lubrication, surface preparation and inorganic finishes. These positions are:
Lubrication Specialist This position offers the opportunity to plan and conduct laboratory programs, develop materials and process specifications and consult with designers on lubricant selection. Requirements include BS or higher degree in Chemical Engineering or Lubrication Engineering, and four or more years experience in lubrication in aircraft and related fields. You should be familiar with general composition, properties and functioning of a wide variety of lubricants and bearing materials.
Oxidation with osmium tetroxide then leads to the required diolamide. No direct comparison of the fivering material has been made with corresponding natural material. But definitive chemical and physical chemical studies have been made to identify all the substances involved in the synthesis, Dr. van Tamelen says. The findings allow "no reasonable structure other than that proposed." Synthesis of complex alkaloids such as strychnine and the curare group has been a severe challenge to scientists. Because of the importance of these compounds in medicine, there have been many efforts to find a commercially useful synthesis for them. It wasn't until the late 1940's that the structure of strychnine was determined—a finding which verified that the synthesis wouldn't be easy. Success came in 1954, however, when Dr. R. B. Woodward and co-workers at Harvard worked out a route involving more than two dozen steps. Swiss and British scientists have determined the structure of the curare complex of alkaloids, which are similar to strychnine. And it is possible to convert strychnine to some of the more valuable curare compounds.
Surface Preparation and Inorganic Finishes Specialists Here are opportunities to participate in planning and conducting laboratory programs, developing materials and process specifications and consulting with designers on the selection of finishes for airplane components. Requirements include BS or higher degree in Chemical Engineering, and at least four years experience in surface preparation and inorganic finishes in the aircraft, or related fields. At Boeing, in the mild, evergreen Pacific Northwest, you'll enjoy the benefits of a dynamic career environment that is conducive to rapid advancement and deeply rewarding achievement.
Send your resume of education and experience today to
Mr. Robert W. King Boeing Airplane Company, Transport Division, P.O. Box 707 · 9ED, Renton, Washington
J*£7JFJTA/£Z
... environment for dynamic career growth
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BRIEFS More research grants have been announced by military agencies: Army Chemical Corps launches a new grant program for support of basic research with nine awards totaling more than $220,000. Areas of investigation: genetic, biochemical, and physiological characterization of infectious microorganisms; the host-parasite relationship in airborne infection; and medical entymology. Controls for Radiation, Inc., gets a contract from the Air Force Missile Development Center to evaluate the biological effects of cosmic radiation. The company will use high energy radiation from cyclotrons and linear accelerators to simulate radiation in outer space, will study the effects on a mammalian cell to evaluate relative hazards of cosmic rays. Rensselaer Polytechnic Institute will continue its study of combustion characteristics of high energy borane fuels under a contract from the Air Force. The research is being done by Dr. W. A. Bauer and Dr. S. E. Wiberley.
