Phosphate derivatives

As of the mid-1990s all commercial phosphoms is manufactured at a few sites around the world. Significant production occurs in Idaho and Montana in the United States, in the Netherlands, in Kazakstan, and in China smaller production occurs in Prance, Russia, and India. A large amount of furnace capacity has been shut down worldwide because of cost pressure from electric power costs, phosphate derived from purified wet acid, and detergent phosphate bans legislated in the Western World. However, as of late 1995, additional production is stiU being brought on line in China. 

Introduction of the cobalt atom into the corrin ring is preceeded by conversion of hydrogenobyrinic acid to the diamide (34). The resultant cobalt(II) complex (35) is reduced to the cobalt(I) complex (36) prior to adenosylation to adenosylcobyrinic acid i7,i -diamide (37). Four of the six remaining carboxyhc acids are converted to primary amides (adenosylcobyric acid) (38) and the other amidated with (R)-l-amino-2-propanol to provide adenosylcobinamide (39). Completion of the nucleotide loop involves conversion to the monophosphate followed by reaction with guanosyl triphosphate to give diphosphate (40). Reaction with a-ribazole 5 -phosphate, derived biosyntheticaHy in several steps from riboflavin, and dephosphorylation completes the synthesis. 

Mannose, one of the eight essential monosaccharides (Section 25.7), is biosynthesized as its 6-phosphate derivative from fructose 6-phosphate. No enzyme cofactor is required. Propose a mechanism. 

Whereas nonionic ethylene oxide adducts discolor badly on contact with sodium hydroxide, phosphate derivatives of these nonionics exhibit good color stability even under these conditions. But in the presence of strong acids poly-oxyethylated phosphate esters undergo hydrolysis to the base nonionic and phosphoric acid. However, the free surface-active acids by themselves show little tendency to hydrolyze. They have a pH value of 2 in aqueous solution. 

The inhibition of Streptococcus mutans adherence to hydroxyapatite with combinations of alkyl phosphates and nonionic surfactants was tested. Seven alkyl phosphate derivatives and three nonionic surfactants were examined for their ability to inhibit the adherence of 3H-labeled cells of S. mutans to hydroxyapatite treated with buffer or parotid saliva. No compound by itself effectively hindered binding of bacteria to hydroxyapatite. A combination of certain of the alkyl phosphates, notably a disodium phosphate of 1-octadecanol, and nonionic surfactant at a 1 1 molar ratio gave a strong inhibition of S. mutans adherence. Treatment with this combination resulted in 98% reduction of adherence. Adsorption of the two types of surface-active agents alone and in combinations was studied using 14C-labeled agents. Electrophoretic measure-... 

Note. When the linkage between monosaccharide units is non-glycosidic (as in the phosphate derivative shown below), use of the glycan terminology is inappropriate other methods of polymer nomenclature should be employed [20],... 

Fig. 3-12 Lipids consist of a triglyceride, three fatty acids such as those in (a) joined to glycerol (b). Other lipids include other functional groups such as phosphate derivatives (c). (Reprinted with permission from W. K. Purves and G. H. Orians, "Life The Science of Biology," pp. 63-81, Copyright 1987 by Sinauer Associates, Inc., Simderland, MA.)...

Clindamycin (93 R = H), an antibiotic obtained by chlorinating linco-mycin, is converted by a species of Streptomyces into inactive phosphorus-containing compounds. These have been shown to be nucleoside 5 -phosphates derived from adenosine, cytidine, guanosine, and uridine. 

In an effort to improve the water solubility of camptothecin, Rahier et al. [50] synthesized four 20-O-phosphate derivatives (VI). These compounds are freely water-soluble, stable to physiological pH, and stabilize the human topo I-DNA covalent binary complex with the same sequence-selectivity as camptothecin itself All four compounds inhibited the growth... 

McGuigan C, Pathirana RN, Balzarini J, De Clercq E. Intracellular delivery of bioactive AZT nucleotides by aryl phosphate derivatives of AZT. J Med Chem 1993 36 1048-1052. 

Breslow demonstrated the catalytic effect of having not only a Lewis acid zinc center but also an auxiliary catalytic center held in close, but non-binding, proximity. An imidazole or thiophenol (81) demonstrated increase in effectiveness in cyclization of a phosphate derivative.706,707 Pyridine pendents on this macrocycle gave a stability for zinc in line with the Irving Williams series for two pyridine and three pyridine pendents.708 A contrast was noted with other metals (Ni, Cu, Cd, Pb, Fe, and In), all of which increase in stability with three pendent arms as does zinc this was attributed to coordination preferences. 

The RNA world hypothesis then rekindled interest in the still open question of the origin of the phosphorus. How could acceptable synthetic routes to the nucleic acids be developed, if it was not even clear which phosphate derivatives were available on the primeval Earth An RNA world is not possible without reactive phosphates or similarly efficient phosphorus compounds Thus, the search for effective phosphorus or phosphate sources continued unabated. 

Although these organic phosphate derivatives are highly toxic and have been used in ways to exploit that property, many organophosphorus compounds have significant utility in the chemical industry. 

Hata, T. and Sekine, M., Silyl- and stannyl-esters of phosphorus oxyacids — intermediates for the synthesis of phosphate derivatives of biological interest, in Phosphorus Chemistry Directed Toward Biology, Stec, W.J., Ed., Pergamon, New York, 1980, p. 197. 

The reactions of [Ru(edta)(H20)] with adenine, and with adenosine and its phosphate derivatives amp, adp, and atp, involve ring closure in a reversibly-formed intermediate containing a unidentate incoming ligand. Both formation (cf. above) and aquation of the intermediates are, on the evidence of the AS values for the amp, adp and atp systems, associative. Rate constants for ring closure are between 0.6 and 4.4 s-1 (165). 

Takayama and coworkers (60) introduced the h.p.l.c. separation technique for such amphiphilic molecules as lipid A, and in earlier experiments they applied paired-ion reverse-phase h.p.l.c. for the preparation of homogeneous fractions deriving from 4,-monophosphated lipid A of S. typhimur-ium. The purified preparations obtained were suitable for f.a.b. - m.s. analysis. However, monophosphated lipid A isolated in this way expressed a considerable heterogeneity with respect to the number and location of 0-acyl residues (60). In order to further improve the purification procedure, as well as to obtain lipid A derivatives suitable for n.m.r. spectroscopy, Qureshi et al. (174) prepared the dimethyl phosphate derivative of S. minnesota (R595) lipid A, which, after purification by reverse-phase h.p.l.c. (C18), could be analyzed by1 H-n.m.r. The n.m.r. spectrum of, for example, the heptaacyl lipid A dimethyl monophosphate fraction, unequivocally revealed 0-acyl substitution [14 0(3-OH)J at position 3 and a free hydroxyl group at position 4 of GlcN(I). 

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