Oxidation ethambutol

An alternative method of synthesis consists of preparing (+) 2-aminobutanol (34.1.3) by redncing ethyl ester of L-2-aminobutyric acid hydrochloride with hydrogen nsing simnlta-neonsly Raney nickel and platinum oxide catalysts. This gives pure (+) 2-aminobutanol. Reacting this with 1,2-dichloroethane in the presence of sodium hydroxide gives the desired ethambutol (34.1.4) [16,17]. 

Allopurinol is used to lower uric acid levels in the treatment of primary gout, as a prophylaxis in myeloproliferative neoplastic disease, for investigational purposes in Lesch-Nyhan syndrome, and as an adjunct with thiazide diuretics or ethambutol (see Chapter 24). Allopurinol acts by inhibiting xanthine oxidase, which converts hypoxanthine into xanthine and in turn becomes oxidized into uric acid. 

The synthetic application of the a-chloro aldehydes has been demonstrated by the preparation of a variety of important chiral building blocks (Scheme 2.35) [26b]. The a-chloro aldehydes could be reduced to the corresponding optically active a-chloro alcohols in more than 90% yield, maintaining the enantiomeric excess by using NaBFU. It was also shown that optically active 2-aminobutanol - a key intermediate in the synthesis of the tuberculostatic, ethambutol - could be obtained in high yields by standard transformations from 2-chlorobutanol. Furthermore, the synthesis of an optically active terminal epoxide was demonstrated. The 2-chloro aldehydes could also be oxidized to a-chloro carboxylic acids in high yields without loss of optical purity, and further transformations were also presented. 

Established Drugs - The oxidative degradation of ethionamide to sulfoxide and other products vitro was studied with relation to activity in tuberculosis. A test for ethionamide sulfoxide in urine was devised so that clinicians could check that patients were ingesting the drug. Clinical and laboratory experience with ethambutol was reported in I5 papers and was summarized by Herman. The pro and con of the isoniazid prophylaxis of tuberculosis was discussed, and the production of hepatic carcinoma in mice with this agent was disclosed.The metabolism of doubly labeled thiocarlide XIII was studied in humans. Blood levels were 10-12 mcg/ml from doses 6 g per day, twice the level seen in rabbits. 

Epinephrine, see Adrenaline Erythromycin, versus the new macrohdes, 21.269 Erythropoietin, pure red cell aplasia, 27.348 status and safety, 16.400 Ethambutol, optic neuropathy, 30.358 Ethylene oxide, dialyser hypersensitivity,... 

Trost has utilized the same class of chiral ligands for the conversion of butadiene oxide (54) into a number of useful chiral building blocks, such as 57 (Scheme 14.11) [67, 68]. In the course of reaction optimization studies, naphthyl-substituted ligand 56 proved optimal and led to the formation of 57 in 96% ee (>99% ee after recrystallization). A powerful illustration of the synthetic utility of such optically active building blocks involved the synthesis of several medicinally important agents, including the tuberculostatic drug ethambutol (58) [68]. 

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