Chikara Kaneko

Synthesis and biological activity of 1α-hydroxyvitamin D3

Abstract Hydroboration of cholesta-1,5-diene-3β-ol followed by alkaline-peroxide oxidation resulted in the formation of 1α- and 2α-hydroxy derivatives of cholesterol in nearly equal amounts. 1α-Hydroxycholesterol was then transformed to 1α-hydroxyvitamin D 3 , via 1α-hydroxycholest-5,7-diene-3β-ol. 1α-Hydroxyvitamin D 3 was as active as 25-hydroxyvitamin D 3 in the stimulation of intestinal calcium transport and bone mineral mobilization in intact rats, and moreover was able to produce both response in anephric rats similar to 1α,25-dihydroxyvitamin D 3 , the active metabolite of vitamin D 3 , as reported originally by DeLucas group.

A new synthetic method of 1α-hydroxy-7-dehydrocholesterol

Abstract Cholesta - 1,4,6 - trien - 3 - one ( 1 ) was converted to 3β - hydroxycholesta - 1,5,7 - triene ( 3 ) via the deconjugation procedure using t-BuOK in DMSO followed by the subsequent reduction with Ca(BH 4 ) 2 . The compound ( 3 ) readily reacted with 4-phenyl-1,2,4-triazoline-3,5-dione to yield the corresponding 1,4-addition product ( 4 ). Epoxidation of 4 with m -chloroperbenzoic acid resulted in the formation of the 1α,2α-epoxide ( 5 ) and the 1β,2β-epoxide ( 6 ) in the ratio 2:3. Reduction of 5 with LAH under reflux in THF afforded the titled compound ( 7 ). The same reduction of 6 gave 2β-hydroxy- and 1β - hydroxy - 7 - dehydrocholesterol ( 8 and 9 ) in the ratio 8:1. The compound ( 4 ) can be obtained in 25% yield from 1 without any purification of the intermediate compounds; cholesta - 1,5,7 - trien - 3 - one ( 2 , a very unstable compound) and 3 . Since 1 is obtained readily from cholesterol in high yield, the present study provides a simple and efficient synthetic method of 1α-hydroxycholecalciferol and is reasonably expected to be applicable in the synthesis of 12,25-dihydroxycholecalciferol and the other metabolites of vitamin D 3 .

Photolysis of 2,6-dicyanopyridine 1-oxides

Abstract Irradiation of 2,6-dicyanopyridine 1-oxide (VIIa) in dichloromethane with > 290 mμ rays gave rise to 2,6-dicyanopyridine (VIIIa; 20%), 5-cyano-2-pyrrolecarbonyl cyanide (IXa) (20%), and an oxazepine (Xa) tentatively assigned as 2,4-dicyano-1,3-oxazepine (Aa; 35%). 4-Methyl-2,6-dicyanopyridine 1-oxide (VIIb) gave similar photo-products. The mechanism implied in these photochemical reactions has been discussed.

New symbolism of electron shifts in resonance theory : Concurrent description of electronshifts and stereospecificities in pericyclic reactions

Abstract A new symbolism for resonance theory is presented which enables one not only to depict the stereochemical aspects but also to provide a very simple selection rule for all concerted pericyclic reactions. The new symbolism uses three kind of arrows; , , and , without altering the significance of the conventional double headed solid arrow symbol for normal noncyclic molecules and non-concerted reactions. A different implication is, however, incorporated into the solid arrow symbol if it is used for cyclic normal molecules and cyclic delocalized systems. Two other new symbols ( and ) are used to depict electron shifts and stereospecificity in pericyclic reactions. The selection rule embodied in the symbolism is based on MO theory and is not merely a convention with no theoretical basis. Furthermore, it can be used correctly without any knowledge of MO theory so long as four rules described in the paper are not violated. Using the new symbolism and rules, resonance theory can be extended to excited state of normal molecules to some extent and to all pericyclic reactions, both of which have been out of reach of the theory. The new arrow symbols can also be used to describe the stereospecificity of a pericyclic reaction, for which no appropriate method of representation has so far been provided.