bishi's previously announced plans to make an initial public offering of UCAR stock. The Blackstone-led company will purchase UCAR's newly issued com mon stock, with the equity portion of the sale valued at $810 million. As part of the leveraged buyout, $280 million of UCAR's debt will be refinanced. UCAR will redeem Mitsubishi's share for $406 million in cash. Mitsubishi orig inally paid Carbide $233 million for its stake in UCAR. Carbide says the sale fits its "strategy of reducing emphasis on noncore busi ness." The joint venture was apparent ly not as successful as first hoped. When the venture was announced at the end of 1990, Carbide chairman Rob ert D. Kennedy said it would create a global alliance that would strengthen the business considerably. But UCAR sales rose only about 8% to $770 mil lion from the end of 1990 to the end of 1993. Kennedy says Carbide will con tinue to work with Mitsubishi in other business areas. Blackstone Group is a private invest ment bank that specializes in investments, mergers and acquisitions; advisory ser vices for corporate clients; and advice on asset management and restmcturing. It is headed by Peter G. Peterson, Com merce Secretary in 1972-73. George Peaff
Cholesterol-lowering agents synthesized
Zaragozic adds have complex core structure
Zaragozic acid A
Key: Black = carbon, red = oxygen, gray = hydrogen
H0 2 CH0 2 COH ϋ υ 2 Γ Zaragozic acid C
Members of a promising class of bio logically active compounds with cho (1994), and Angew. Chem. Int. Ed. Engl,reocenters one at a time, using a num lesterol-lowering properties, called 33, 2190 (1994)]. ber of reactions, including a Sharpless zaragozic acids or squalestatins, have In addition, David A. Evans and co asymmetric dihydroxylation." been synthesized for the first time. The zaragozic acids and squalestatins workers in the department of chemis Organic chemistry groups at several try at Harvard University have com were discovered independently in fun universities have been pursuing the pleted a second synthesis of zaragozic gal cultures about five years ago by challenging total synthesis of these acid C. A paper on their work will be groups at Merck & Co. in Rahway, N.J., complex structures. Now, two groups published next month in the Journal of and Madrid, Spain, and at Glaxo Group have reached the goal simultaneously. the American Chemical Society. Research Ltd., Greenford, England. The Erick M. Carreira and Justin Du Bois Zaragozic acids A and C have iden Merck scientists named them after the of the division of chemistry and chem tical core structures and differ only in natural source where they were found—a ical engineering at California Institute their side chains. They both have high water sample from the Zaragoza region of Spain. Glaxo researchers named them of Technology synthesized zaragozic biological activity. acid C [/. Am. Chem. Soc., 116, 10825 Carreira says his group's synthetic squalestatins because they inhibit the (1994)]. Zaragozic acid A was prepared strategy "relies on acyclic stereocontrol enzyme squalene synthase. Scientists at by K. C. Nicolaou, Alan Nadin, James to prepare a functionalized intermedi the two companies have since isolated E. Leresche, Eddy W. Yue, and Susan ate, which is converted to the dioxabi- dozens of these compounds. La Greca of the chemistry departments cyclooctane core common to the zara The compounds "have generated a lot at Scripps Research Institute, La Jolla, gozic acids and squalestatins." Nico of interest in the academic community Calif., and the University of California, laou says his group "started with a flat, because of their biological activity and San Diego [Angew. Chem., 106, 2312prochiral molecule and built on the ste- complex structure," Carreira tells C&EN. NOVEMBER 21,1994 C&EN 9
NEWS OF THE WEEK "At least 10 different groups that I know of have been working on the synthesis/' The compounds "are very potent inhibitors of squalene synthase—the enzyme in all of our bodies that's responsible for the first committed step in cholesterol biosynthesis. They were identified early on as really exciting leads toward very powerful cholesterol-lowering agents." Nicolaou says in vitro and in vivo r e suits show zaragozic acid A lowers cholesterol levels dramatically. Zaragozic ac-
ids also inhibit Ras farnesyl transferase, which is implicated in cancer—particularly colon and pancreatic cancer. He notes that "there has been a lot of manipulation of these compounds, mostly by Glaxo and Merck, to fine-tune their biological activity—which maybe is not perfect right now." The syntheses should make it easier to produce analogs—some perhaps more biologically active, more specific in their action, or safer to administer than the natural products. Stu Borman
Rhone Poulenc Rorer to spur R&D on gene therapy Rhône-Poulenc Rorer (RPR) has launched an aggressive effort to develop cell and gene therapy. The pharmaceutical unit of French chemical and pharmaceutical giant Rhône-Poulenc has created a new division, RPR Gencell, to spur research and product development in cell and gene therapy. And it has formed a novel col-
laborative network with 14 French and U.S. companies and research organizations to advance its efforts. RPR Gencell, based in Collegeville, Pa., will tie together R&D efforts by RPR and its 14 partners on gene discovery, sequencing, and expression; on development of vectors for genetic transformation; and on cell selection and ex vivo cellular manipulation. The new division will focus initially on oncology, nervous Rhône-Poulenc Rorer to collaborate system disorders, and carwith 14 organizations diovascular disease. Alliances between major Organization/location Area of collaboration pharmaceutical companies Applied Immune Sciences3 Gene therapy methods and small R&D firms have Santa Clara, Calif. become common. Under Centre National de Gene transfer, nervous difficult economic and comRecherche Scientifique system disorders Vitry, France petitive conditions, large companies turn to small Darwin Molecular Gene therapy for cancer Seattle firms to access new technolGénéthon ogies and potential new Gene discovery for Paris genetic diseases products. In return, small Genetix Pharmaceuticals Multiple drug resistance companies and researchNew York City genes, retroviral products based organizations gain Genopoietic Gene therapy for cancer access to the large compaParis nies' resources and infraInstitut Gustave Roussy Adenovirus vectors structure for product develParis opment, clinical testing, regInstitut Pasteur Lille High-density lipoprotein ulatory assessment, and Lille, France cholesterol manufacturing. Introgen Therapeutics Two antitumor programs But RPR Gencell is Houston unique in attempting to Lawrence Berkeley Laboratory Genes for diabetes, Human Genome Center obesity, atherosclerosis pull together so many difBerkeley, Calif. ferent research organizaPasteur Merieux Connaughtb Cell and gene therapy, tions. Its partners include and affiliate, Virogenetics immunotherapy biotechnology companies, Lyons, France two laboratories particiTransgène Adenovirus vectors for pating in the worldwide Paris gene therapy applications Human Genome Project, Université Louis Pasteur Lipid-based molecules two major cancer centers, for gene transfer Strasbourg and several research instia Rhône-Poulenc Rorer acquired a 37% stake in the company in June 1993. b Company wholly owned by Rhône-Poulenc. tutes and university departments. About 150 sci10
NOVEMBER 21,1994 C&EN
entists at RPR will cooperate with the program. RPR Gencell expects synergies within the network to enable the division to translate discoveries into products more efficiently than can a single company. Over the past 18 months, RPR and RPR Gencell have signed individual agreements with each member—with separate funding, licensing, and royalty arrangements—but they hope to foster a collaborative atmosphere among partners. By the end of 1994, RPR will invest $300 million in RPR Gencell's internal and partner programs. This includes $113 million for a 37% stake in Applied Immune Sciences and $5 million in funding for Darwin Molecular. Next year, RPR expects to spend about $100 million more, depending on progress made. Funding commitments will be based on "performance" and "milestones." RPR Gencell and its partners have six therapies in clinical trials, with three more to start trials soon. Ann Thayer
Shuttle mission probes atmospheric chemistry Space shuttle Atlantis returned to Earth last week after almost 11 days in orbit conducting what its organizers call "the most comprehensive examination ever made of the Earth's atmosphere and the solar energy that drives its chemistry." Part of the National Aeronautics & Space Administration's Mission to Planet Earth, the ATLAS-3 mission (Atmospheric Laboratory for Applications & Science) carried seven instruments. The instruments studied the Sun's energy output and the chemical composition of the middle atmosphere, and how they affect global ozone levels. The international crew of six astronauts, including one from France, also deployed and retrieved a German-built satellite carrying two instruments. One instrument observed gases in the middle atmosphere, the other measured nitric oxide and hydroxyl in the middle atmosphere and lower thermosphère. And the crew performed onboard life sciences and microgravity processing experiments, including protein crystal growth tests. This was the third—and apparently final—mission in the ATLAS series launched in March 1992. Up to 10 missions were originally planned to cover
