Upjohn, introduction

Diels-AUer reactions. This diene can serve as a precursor to the highly oxygenated cyclohexane derivative shikimic acid (3), as shown in Scheme 1. Oxidative desilylation of the Diels-Alder adduct 2 could not be effected with peracids, but was effected by cis-dihydroxylation (Upjohn procedure, 7, 256-257) followed by p-elimination of (CH3)3SiOH with TsOH. Introduction of the 4a,5P diol system was effected indirectly from the 4a,5a-epoxide in several steps, since direct hydrolysis of the epoxide resulted in a mixture of three triols.1... 

Strand LM, Cipolle RJ, Morley PC. 1992. Pharmaceutical care An introduction. In Current Concepts, p. 1. Kalamazoo, MI Upjohn Company. 

Strand L, CipoUe RJ, Morley PC. Pharmaceutical care an introduction. In Current concepts, 1992. Kalamazoo, Ml The Upjohn Co., 1992 15. 

Other reoxidants which minimize overoxidation are f-butyl hydroperoxide in the presence of Et4NOH [4], tertiary amine oxides, and most importantly N-methylmorpholine A -oxide (NMO) (Upjohn process) [14], although for tri- and particularly tetrasubstituted alkenes as substrates, trimethylaminoxide is superior to NMO [14 c], The introduction of potassium hexacyanoferrate(III) in the presence of potassium carbonate [15] substantially improved the selectivities in chiral dihydroxylations [16], although it was first reported as a co-oxidant in 1975 [17]. Industrial efforts led to an electrochemical oxidation of potassium ferrocyanide to ferricyanide in order to use electricity as the actual co-oxidant [18]. 

A few years after the introduction of Taxol in 1996, further phytogenic anticancer drugs were launched to treat advanced cancers. Topotecan, marketed by Smith Kline Beecham under the trade name of Hycamtin, was approved by the FDA to treat ovarian cancers that have resisted other chemotherapy drugs. Furthermore, irinotecan was introduced by Pharmacia Upjohn under the trade name of Camptosar for the treatment of metastatic cancer of the colon or rectum. Both compounds are derivatives of camptothecin which was isolated from the Chinese tree Camptotheca acuminata, well known in Chinese Traditional Medicine for anticancer treatment [65]. Isolation of the bioactive principle camptothecin and its structure elucidation had already been performed in 1966... 

These issues are summarized in the extremely simplified mechanism given in Scheme 8.14. All osmylation reactions ultimately afford the osmate ester shown, although the mechanism for this step has been controversial. Note that the osmium is reduced over the course of the reaction. In efforts to minimize the amount of toxic osmium used in these reactions, catalytic methods using a variety of stoichiometric reoxidants for osmium were introduced, beginning with the introduction of KCIO4 in 1917 by Hofmann [66] and including the convenient Upjohn process, which uses N-methylmorpholine-A-oxide for this purpose [67]. 

While Merck, beginning in 1949, and Sobering, in 1951, manufactured cortisone from deoxycholic acid, Peterson and Murray, biochemist and microbiolc st, respectively, with the Upjohn Company, chose to attack the problem of the introduction of 11-oxygen by the potentially more direct, microbiological method. They have said (P-723) that they were stimulated to enter this fi d by the successes of the Mamoli school. They were also encouraged, early in their work, by the report of Hechter and collaborators that perfusion of deoxycorticosterone through isolated adrenal glands resulted in the formation of corticosterone by enzymatic 11/3-hydroxylation. 

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