connective tissue metabolism. In sit uations in which natural elastase inhibitor is compromised, unchecked human leukocyte elastase is very destructive. Such cases occur through genetic deficiencies and, in the case of emphysema, usually as a result of cigarette smoke. The Syntex scientists worked with benzoxazinones, reagents known to substitute for the normal substrate of elastase and form acyl enzyme intermediates. Normally, such en zyme intermediates are broken down rapidly by enzyme catalyzed deacylation. By using steric effects to block deacylation, Krantz and co workers showed that the lifetime of acyl elastases derived from benzox azinones can be dramatically in creased. "Very few strategies that rely on steric effects to inhibit enzymes ex ist/' Krantz says. He points out that the addition of an isopropyl group to the amino group of 2-aminobenzoxazinone and introduction of an ethyl group in the 5 position of the benzoxazinone ring increases the potency of the compound as an inhibitor of human leukocyte elas tase by a factor of 67,000. Rudy Baum, San Francisco
Chemists designing molecular-scale Lego
Toronto Chemists from the University of Texas, Austin, have made progress in fashioning a set of Lego building blocks on a molecular scale. Such small, rigid, linear components of well-defined lengths and connecting capabilities will be useful for build ing racks, nets, and scaffolding for study of other molecular groups held at fixed distances and angles from one another. At an organic chemistry session, CH 3 0 2 C
C0 2 CH 3
Polypropellanes afford rigid rods of known dimensions with versatile connecting groups
chemistry professor Josef Michl said he chose polypropellanes (polyl,3-bicyclo[l.l.l]pentylenes) as the first type of building block in his Lego set. Working with graduate students Piotr Kaszynski and Adrienne Friedli, he tailored these mo lecular rods to length according to the number of propellane units. Michl calls such compounds [n]staffanes, where η is the number of propellane units. Work with crystallographer Vin cent Lynch established lengths of each rod, which run about 1.82 A for each propellane unit and 1.47 A for each bond stringing them to gether. Widths are 5 to 6 A. Rods three propellanes long crystallize as rotational conformers that the Austin group calls syn, anti', and anti", each with a slightly different length. Building on work of earlier in vestigators, the Texas chemists made propellane itself by treatment of l,l-dibromo-2,2-bis(chloromethyl)cyclopropane with methyllithium. Radical chain transfer reaction of propellane with methyl formate yielded methyl propellane-1-carboxylate and bipropellane-1-carboxylate. Further reaction of the pro pellane-1-carboxy late with phosgene yielded polypropellanes one to four units long with a carbomethoxy group at each end. Such end groups will furnish means of linking rods to one another and to other mole cules. As an approach to probing these systems, Michl showed that he could distinguish individual methylene protons and carbon atoms by pro ton and carbon-13 nuclear magnet ic resonance. These differed accord ing to location and rod length. He also showed different coupling con stants of phosphorus-31 atoms in rods of different lengths bearing phosphonate groups at each end. These molecular rods have the desired stability to heat and air, decomposing at about 300 °C. Their propellane components are trans parent in ultraviolet-visible spectros copy. Further work at Austin cen ters on designing electrically con ducting and insulating rods and re versible or irreversible connections by end groups. Stephen Stinson, New York
Novel route taken to arenesulfonates
Toronto A homogeneous conversion of alkyl halides to arenesulfonate esters has been developed that avoids use of silver salts. Describing the meth od at an organic chemistry session, organic chemistry professor Roger C. Hahn of Syracuse University noted that it has potential for making in termediates for drugs and pheromones cheaply and on a large scale. Quaternary ammonium halides catalyze exchange of alkyl halides with such readily available com pounds as methyl p-toluenesulfonate. Distillation of a low-boiling methyl halide drives the reaction to completion. Use of heterodihalides enables chemists to make difunctional products. For example, working with organic chemistry professor Jan Tompkins of the State University of New York Health Sciences Center, Syracuse, Hahn reacted 2-bromo-l-chloroethane with methyl p-toluenesulfonate to get 2-chloroethyl p-toluenesulfonate with evolution of methyl bro mide. Nuclear magnetic resonance spectra showed that the reaction mixture contained only 5% of the 2-bromoethyl ester and traces of starting materials. Substitution of chloroiodomethane in the reaction yielded a mix ture of chloromethyl and methylene p-toluenesulfonates. The Syracuse chemists are working to optimize the reaction as a means of making either of these useful intermediates. Though chloroiodomethane is costly and hard to make, Hahn had previously devised an easier, inex pensive route to this difunctional intermediate [/. Org. Chem., 53,1331 (1988)]. Heating of readily available bromochloromethane with methyl iodide in the presence of a quater nary ammonium chloride ion ex change resin gave a 92% yield of chloroiodomethane, 99% pure. Dis tillation of methyl bromide from the reaction drove it to completion. Stephen Stinson, New York June 27, 1988 C&EN
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