Dihydroxy-addition

B. Oxygen, Nitrogen, or Sulfur on One or Both Sides 15-46 Hydroxylation (Addition of Oxygen, Oxygen) Dihydroxy-addition... 

The addition of hydroxy groups to the carbon-caibon double bond of an alkene (equation 1) is classed under the lUPAC nomenclature for transformations as a dihydroxy addition. Many reagents can bring about this transformation,which can proceed in a syn or anti manner, as shown in equation (2), and the type of addition which occurs depends on the reagent. 

Hydroxylation (Addition of Oxygen, Oxygen) Dihydroxy-addition... 

The osmium tetroxide produces a dihydroxy-addition to the alkene. 

Reactions in which a product remains in the him (as above) are complicated by the fact that the areas of reactant and product are not additive, that is, a nonideal mixed him is formed. Thus Gilby and Alexander [310], in some further studies of the oxidation of unsaturated acids on permanganate substrates, found that mixed hlms of unsaturated acid and dihydroxy acid (the immediate oxidation product) were indeed far from ideal. They were, however, able to ht their data for oleic and erucic acids fairly well by taking into account the separately determined departures from ideality in the mixed hlms. 

This cleavage is a retro aldol reaction It is the reverse of the process by which d fruc tose 1 6 diphosphate would be formed by aldol addition of the enolate of dihydroxy acetone phosphate to d glyceraldehyde 3 phosphate The enzyme aldolase catalyzes both the aldol addition of the two components and m glycolysis the retro aldol cleavage of D fructose 1 6 diphosphate... 

In the treatment of diseases where the metaboUtes are not being deUvered to the system, synthetic metaboUtes or active analogues have been successfully adrninistered. Vitamin metaboUtes have been successfully used for treatment of milk fever ia catde, turkey leg weakness, plaque psoriasis, and osteoporosis and renal osteodystrophy ia humans. Many of these clinical studies are outlined ia References 6, 16, 40, 51, and 141. The vitamin D receptor complex is a member of the gene superfamily of transcriptional activators, and 1,25 dihydroxy vitamin D is thus supportive of selective cell differentiation. In addition to mineral homeostasis mediated ia the iatestiae, kidney, and bone, the metaboUte acts on the immune system, P-ceUs of the pancreas (iasulin secretion), cerebellum, and hypothalamus. 

Potential 2,5-dihydroxy compounds (185) exist in the dicarbonyl forms (186). Succinic anhydride (186 Z = O) on silylation is converted into 2,5-bis(trimethylsilyloxy)furan (187) the latter compound readily participates in Diels-Alder addition reactions (80TL3423). Reaction of thiosuccinic anhydride (186 Z = S) with the triphenylphosphorane Et02CH=PPh3 gives a product which exists in the aromatic form (188) (75LA1967). 

Catechin and epicatechin are two flavanols of the catechin family. They are enantiomers. The capillary zone electrophoresis (CE) methods with UV-detection were developed for quantitative determination of this flavanols in green tea extracts. For this purpose following conditions were varied mnning buffers, pH and concentration of chiral additive (P-cyclodextrin was chosen as a chiral selector). Borate buffers improve selectivity of separation because borate can make complexes with ortho-dihydroxy groups on the flavanoid nucleus. 

When 3a,17a-dihydroxy-5jS-pregnane-ll,20-dione is allowed to react at room temperature overnight with sodium borohydride in aqueous methanol, no crystals form and only 5j5-pregnane-3a,l ljS,17a,20j5-tetrol is isolated in good yield. If the reaction is halted at the end of 3 h y the addition of water and extraction with chloroform, it is possible xo obtain a 55% yield of 3a,17a,20jS-trihydroxy-5j5-pregnan-ll-one, mp 218-220°,after recrystallization of the chloroform residue from aqueous methanol. The analytical sample, crystallized once more, has mp 219.0-220.6° [a][, 36° (acetone), reported mp 220° [aJu 38°. 

P, lp-Dihydroxy-5fi,6P-difluorom thyleneandrostane Diacetate 17)- A solution of 2.25 g (0.006 mole) of 3, 17/ -dihydroxyandrost-5-ene diacetate, mp 164-166° in diglyme (100 ml), is treated with 7.2 g (0.048 mole) of sodium chlorodifluoroacetate as previously described. The crude product, mp 123-130°, is crystallized from hexane affording unchanged olefin (16 1.64 g) mp 163-165°. The mother liquor is adsorbed from hexane on Florisil (100 g). Elution with hexane-ether (4 1) furnishes an additional 0.3 g of the... 

The oxygen is then replaced by nitrogen and a solution of sodium hydroxide (5 g) in methanol (100 ml) and water (50 ml) is added. After agitation for 70 min at ambient temperature, followed by the addition of acetic acid (10 ml), the mixture is poured into water (4 liters). The precipitate is isolated by filtration, washed with water and dried in an air draft at 100° to yield 47 g of crude product. This material is dissolved in methanol (1.5 liters) and ethyl acetate (500 ml) and the solution concentrated to half its initial volume. Ethyl acetate (500 ml) is added and the solution is cooled to yield 29.4 g (63%) of 3, 17a-dihydroxy-16f -methyl-5a-pregnan-20-one mp 255-260° [ajp 45.6° (diox.). 

A solution of 0.38 g of the diazoketone in 2 ml of acetic acid is heated 0.5 hr at 100-105°. Removal of the solvent under reduced pressure and crystallization of the residue from acetone-ether gives 0.27 g of 1 la,21-dihydroxy-pregn-4-ene-3,20-dione 11,21-diacetate mp, 144-146° [a]o 156° (CHCI3). An additional 60 mg of this product is obtained by chromatography of the mother liquor (total yield 72%). 

Dihydroxypteridine was expected to undergo hydration but, a priori, it was difficult to decide whether covalent hydration would occur across the 3,4- or the 7,8-position, or both. Kinetic and spectroscopic evidence now indicate that addition of water occurs much more rapidly across the 3,4-positions (and, hence, that the energy of activation must be less for this site), but the 7,8-water-adduct is thermodynamically the more stable. With time, the concentration of the species hydrated in the 3,4-position reaches a maximum (about 64% of the total concentration). Thereafter, it falls steadily and the concentration of the 7,8-adduct rises until, at equilibrium, the latter accounts for 92% of the total and the 3,4-adduct for only 7.6%. In 2,6-dihydroxy-4-methylpteridine, the methyl group drastically reduces the extent of water addition to the 3,4-position but does not significantly affect 7,8-addition, so that, spectroscopically, only a first-order conversion of anhydrous molecule into the 7,8-water-adduct is observed. ... 

Preparation of 9a-Bromo-110,17a 1 Trihydroxy-16 -Methyl-4-Pregnene-3,20-Dione 21-Acetate To a mixture of 620 mg of 17a,21-dihydroxy-16/3-methyl-4,9(11 )-pregnadiene-3,20-dione 21-acetate and 330 mg of N-bromosuccinimide in 10 ml of dioxane and 3.2 ml of water cooled to 10°C was added 1.8 ml of cold 1 M aqueous perchloric acid. The mixture was stirred at 15°C for 3 hours. Excess N-bromosuccinimide was destroyed by addition... 

To approximately 1.3 g of hydrogen fluoride contained in a polyethylene bottle and maintained at -60°C was added 2.3 ml of tetrahydrofuran and then a solution of 500 mg (0.0012 mol) of 6a-fluoro-9/3,11/3-epoxy-16a-methyI-17a,21 -dihydroxy-1,4-pregnadiene-3,20-dione-2T acetate in two ml of methylene chloride. The steroid solution was rinsed in with an additional 1 ml of methylene chloride. The light red colored solution was then kept at approximately -30°C for 1 hour and at -10°C for 2 hours. At the end of this period it was mixed cautiously with an excess of cold sodium bicarbonate solution and the organic materiai extracted with the aid of additional methylene chloride. 

The cold solution was then allowed to stand overnight and all crystalline material filtered through a sintered glass filter. The filtrate was treated with an additional 300 ml of concentrated hydrochloric acid to yield a heavy white precipitate. The precipitate was filtered, dried and combined with the Initial precipitate obtained as described above. The combined precipitated product, 3A-dihydroxy-N-[3-(4-hydroxyphenyl)-1-methyl-n-propyl-/ henethylamine hydrochloride, had a melting point of about 184°Cto 186°C after recrystallization from boiling 4N hydrochloric acid. 

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