Du Vigneaud

Prepn Weiss and Stekol J Am Chem Soc 73 2497 I95I see also du Vigneaud et al. J Biol Chem 143 60 1942 Biological synthesis Greenberg Methods Enzymol 5 943 1962.]... 

Oxytocin [50-56-6] M 1007.2, m dec on heating, [a] -26.2"(c 0.53, N AcOH). A cyclic nonapeptide which was purified by countercurrent distribution between solvent and buffer. It is soluble in H2O, rt-BuOH and isoBuOH. [Bodanszky and du Vigneaud J Am Chem Soc 81 2504 1959 Cash et al. J Med Pharm Chem 5 413 1962 Sakakibara et al. Bull Chem Soc Jpn 38 120 1965 solid phase synthesis Bayer and... 

V. du Vigneaud (New York) biochemically important sulfur compounds, especially the first synthesis of a polypeptide hormone. 

FIGURE 3.4 Deprotection of functional groups by reduction with sodium in liquid ammonia [du Vigneaud et al., 1930]. As in Figure 3.3, except reduction is effected by solvated electrons and protons are provided by water at the end of the reaction. Excess sodium is destroyed by NH4C1. This is a simplified presentation of the reaction. AH benzyl-based protectors as well as -Arg(N02)-, -Arg(Tos)-, and -His(Tos)- are sensitive to sodium in liquid ammonia. 

The first indication that methylation occurred in vivo was probably the observation that if pyridine was given to animals, methyl pyridine was excreted in their urine (His, 1887). From his studies on the fate of administered tellurides and their excretion as methyl telluride, Hofmeister (1894) proposed methylation might be a normal metabolic process in animals. This was conclusively established as a result of extensive work from du Vigneaud and his group between the late 1930s and 1955. Standard nutritional experiments with rats were combined with pioneering studies on the metabolism of 2H-labeled compounds (see du Vigneaud, 1952). 

The question therefore arose about the fate of the methyl group from methionine. When minimal amounts of methionine were used to supplement the diet of rats given homocysteine as their main source of sulfur, the rats did not usually thrive, and at death had fatty accumulations in their livers. Best and his co-workers had earlier reported the efficacy of choline as a lipotropic agent, facilitating the mobilization of fat from the liver. Du Vigneaud therefore tried supplementing homcys-... 

The mechanism of transmethylation was then examined. A series of deuterium-labeled methylated compounds were synthesized by du Vigneaud s group, including arsenocholine, trimethylamine, dimethyl-glycine, and dimethylthetin. Of these only betaine and dimethylthetin served as methyl donors. In 1949 Dubnoff found that choline could only act as a donor under aerobic conditions, when it was oxidized to betaine. 

Vincent Du Vigneaud United States sulfur compounds of biological importance, synthesis of polypeptide hormone... 

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