Synthesis and biological activity of 1α-hydroxyvitamin D3

Kaneko, Chikara; Yamada, Sachiko; Sugimoto, Akihiro; Eguchi, Y.; Ishikawa, Masayuki; Suda, Toshio; Suzuki, Michiko; Kakuta, Saburo; Sasaki, Satoshi

doi:10.1016/0039-128x(74)90142-1

Cited by 31 publications

(4 citation statements)

References 21 publications

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“…calcium mediated by 1-fluorovitamin D3, on the other hand, did not maximize until 24 h after dosage and did not abruptly decline, but rather remained elevated or perhaps slowly declined throughout the 48-h test period. Similarly, the intestinal-calcium transport response to la-OH-D3 maximized at 12 h, but that of 1-fluorovitamin D3 maximized only after 24 h. la-OH-D3 was able to increase both serum calcium concentration and intestinal-calcium transport rate in bilaterally nephrectomized rats as expected (Holick et al, 1973;Kaneko et al, 1974). In contrast, nephrectomy eliminated the bone-calcium mobilization response to 1 pg of 1-fluorovitamin D3 and vastly diminished the intestinal-calcium transport response (Table IV).…”

Section: Biological Evaluationsupporting

confidence: 56%

1-Fluorovitamin D3, a vitamin D3 analog more active on bone-calcium mobilization than on intestinal-calcium transport

Napoli¹,

Fivizzani²,

Schnoes³

et al. 1979

Biochemistry

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Section: Biological Evaluationsupporting

confidence: 56%

1-Fluorovitamin D3, a vitamin D3 analog more active on bone-calcium mobilization than on intestinal-calcium transport

Napoli¹,

Fivizzani²,

Schnoes³

et al. 1979

Biochemistry

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“…1A). About 3% of la-hydroxytachysterol3 had been found, a material not reported by Kobayashi (5) but reported by other workers (6). The formation ofundesirable byproducts (i.e., decomposition ofmaterials) continued at a steady rate and, at the leveling-off point for la-OHpreD3 formation, these products amounted to 45% of the total reaction mixture (Fig.…”

mentioning

confidence: 52%

Efficient photochemical formation of 1 alpha-hydroxyprevitamin D3.

Dauben¹,

Phillips²,

Jefferies³

1982

Proc. Natl. Acad. Sci. U.S.A.

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Control of the band width of the irradiating light between 280 and 310 nm and of the temperature of the reaction permits formation of la-hydroxyprevitamin D3 in yields of over 80%, at 40-60% conversion of the la-hydroxyprovitamin D3. The procedures developed permit doubling the photochemical yield of the la-hydroxyvitamin D3 compounds which are the major circulatory forms of vitamin D3.The utility of la-hydroxyvitamin D derivatives in the treatment of various medical disorders arising from faulty calcium metabolic processes has led to the preparation of a wide variety of hydroxylated sidechain derivatives (for reviews of the physiology of vitamin D, see refs. 1-3). In the preparation of these materials, the major attention often has been directed only to the preparation of the material, without optimization of the overall yield. It was early found by Barton (4) that the standard irradiation condition utilized to prepare previtamin D3 (preD3) in good yield gave a much lower yield (15-25%) when applied to the preparation of la-OHpreD3 and its side chain-hydre ylated derivatives.7-dehydrocholesterol in dry ether was irradiated at the given temperature with 300-nm light from a CMX-4 laser (6 kV per pulse; 15 pulses per sec; 5 mW; rhodamine 6-G in methanol) and the reaction was monitored by HPLC with progesterone as the standard. Under the HPLC conditions used, la-hydroxyprovitamin D3 and la-hydroxylumisterol could not be separated, and therefore the sum of the two compounds is reported here. At 0C, the formation of la-OHpreD3 leveled off at a maximal yield of about 22%; the amount of the provitamin continued to decrease, 60% having been consumed at this leveling-off stage (Fig. 1A). About 3% of la-hydroxytachysterol3 had been found, a material not reported by Kobayashi (5) but reported by other workers (6). The formation ofundesirable byproducts (i.e., decomposition ofmaterials) continued at a steady rate and, at the leveling-off point for la-OHpreD3 formation, these products amounted to 45% of the total reaction mixture (Fig. 1B).When the laser irradiation was conducted at -21°C, quite a different reaction profile was found. The formation of la-HO la-Hydroxyprevitamin D3 la-Hydroxyprovitamin D3 It was noted that UV light in the ranges below 275 nm and above 310 nm, especially between 310 and 330 nm, gave rise to undesirable products.The problem of synthesis recently has been investigated in detail at room temperature by Kobayashi and his collaborators (5) using monochromatic UV light obtained from a spectroirradiator for analytical irradiations and using a newly reported filter solution (light between 280 and 310 nm) for preparative irradiation. These studies showed that the maximal yield of lahydroxyvitamin D was obtained by using their filter solution III, the results being 39% la-OHD3, 20% starting la-hydroxyprovitamin D3 (1-OHproD3) and 41% undesirable byproducts (i.e., a 50% yield of vitamin D based upon recovered preD3 precursors). EXPERIMENTALThe effect of bandwidth of the incident light and of the ...

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“…The dienol7 was prepared by the method of Kaneko et al (6). An improvement to this procedure was found to be one in which cholesta-1.5-diene-3-one was purified by chromatography on silicic acid prior to its reduction to 7.…”

Section: Cholcsta-i5-diene-3p-o1(7)mentioning

confidence: 99%

“…The dienol7 was prepared by the method of Kaneko er al. (6). It was, however, unstable in pyridine, and underwent a rapid, irreversible rearrangement as evidenced by 'Hmr spectroscopy.…”

mentioning

confidence: 99%

The solvolysis of the p-toluenesulphonate and methanesulphonate of cholesta-1,5-diene-3β-ol

Georghiou¹,

MacDiarmid²

1980

Can. J. Chem.

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PARIS E. GEORGHIOU and MARGARET A. MACDIARMID. Can. J . Chem. 58, 1759Chem. 58, (1980. In sittr preparations of 3P-tosyloxycholesta-1,5-diene and 3P-mesyloxycholesta-1.5-diene were subjected to methanolysis and hydrolysis. The products obtained were those of nucleophilic displacement with inversion at C3, a s well a s the epimers formed with retention of stereochemistry. No cyclized products could be isolated.Can. J . Chem. 58, 1759Chem. 58, (1980. Nous decrivons la preparation in situ du tosylate et du mtsylate de cholesta-1.5-diene-3P-01. L e methanolyse et I'hydrolyse en milieu acetonique aqueux deces deux composes conduit a la formation aussi bien des produits avec inversion que des produitsavec retention de configuration en position 3. On n'a pas observe experimentalement la formation d'un produit d e cyclisation.Baldwin recently proposed a set of simple empirical rules (1) to predict the relative facility of different ring closures. According to the these rules, both 3-exo-tet and 3-exo-trig ring closures leading to the formation of three-membered rings are favoured processes. The well-known "icholesteryl" solvolytic rearrangement (2) of cholesteryl tosylate 1 to form the C3-C5 bicyclo ring A steroids 2 or 3 is an example of the former type. Here, the breaking of the C3-oxygen bond of the tosylate 1 is exocyclic to the 3-membered ring formed in the reaction and the geometry of C3 is tetrahedral (see Scheme 1):There are no simple examples of the 3-exo-trig ring closure resulting in the formation of a threemembered carbon ring in steroids."'Author to whom correspondence should be addressed. 'Revision received May 12, 1980. 'Laing and Sykes (3) however, have reported that the attempted tosylation of 5a-cholest-1-en-3P-01, 4, resulted in the It appeared to us that cholesta-13-diene-3P-ol,7 could serve to ascertain whether or not a preference is exhibited for one type of three-membered ring formation over the other. In principle, the C1-C5 bicyclo ring A-type compound4 8 could be formed via a 3-exo-trig ring closure with concommitant elimination. On the other hand, the icholesteryl-type product 9 could be formed via the 3-exo-tet mode (see Scheme 2):formation of Ia,5-cyclo-5a-cholest-2-ene, 5. A mechanism was proposed which involved a 1,3-transannular hydrogen shift in the tosylate 6 which is too unstable to be isolated. The second step in the rearrangement (step ( b ) ) could be regarded a s an example of a 3-exo-trig ring closure in which C5 is an incipient carbonium ion which could be considered to be approximately trigonal:?The preparation of another Cl-C5 bicyclo ring A steroid, Ia,5-cyclo-5a-cholestan-3~-ol-6-one in which ring B is functionalized has been reported by Laing and Sykes (4). These results, however, could not be duplicated (see ref. 5).

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Synthesis and biological activity of 1α-hydroxyvitamin D3

Cited by 31 publications

References 21 publications

1-Fluorovitamin D3, a vitamin D3 analog more active on bone-calcium mobilization than on intestinal-calcium transport

1-Fluorovitamin D3, a vitamin D3 analog more active on bone-calcium mobilization than on intestinal-calcium transport

Efficient photochemical formation of 1 alpha-hydroxyprevitamin D3.

The solvolysis of the p-toluenesulphonate and methanesulphonate of cholesta-1,5-diene-3β-ol

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