Jun-ichi Oshida

Synthesis of 24,24-difluoro- and 24ξ-fluoro-25-hydroxyvitamin D3

Abstract From cholenic acid 24,24-difluoro-25-hydroxyvitamin D 3 and 24ξ-fluoro-25-hydroxyvitamin D 3 were prepared.

Synthesis of 2β-fluoro-1α-hydroxyvitamin D3

Abstract 2β-Fluoro-1α-hydroxyvitamin D 3 ( 3 ) was prepared from 1,2α-epoxy-cholest-5-en-3β-yl tetrahydropyranyl ether( 1a via 2β-fluorocholest-5-ene-1α, 3β-diol( 2 ).

Studies on organic fluorine compounds. Part 37. Studies on steroids. Part 78. Synthesis of 24,24-difluoro- and 24ξ-fluoro-25-hydroxyvitamin D3

To clarify the physiological significance of C-24 hydroxylation in vitamin D3 metabolism, vitamin D3 compounds blocked at C-24 by fluorine substituents, namely 24,24-difluoro-25-hydroxyvitamin D3(1) and 24ξ-fluoro-25-hydroxyvitamin D3(2) have been synthesized from 3β-hydroxychol-5-en-24-oic acid (13).

Synthesis of 26,26,26-trifluoro-25-hydroxy and 27-nor-26,26,26-trifluoro-25-hydroxyvitamin D3

Two new fluorinated 25-hydroxyvitamin D3 analogs, 26,26,26-trifluoro- 25-hydroxy (1) and 27-nor-26,26,26-trifluoro-25-hydroxyvitamin D3 (2), were prepared from 24-phenylsulfonyl 25,26,27-triorcholest-5-en-3β-yl tetrahydropyranyl ether (3).

Novel vitamin D3 derivatives, 26-Homo-Δ22-dehydro-1α, 25(S)-dihydroxyvitamin D3 and 26-Homo-Δ22-dehydro-1α, 25(R)-dihydroxyvitamin D3: Preferential activity in c-myc mRNA production and in induction of phenotypic differentiation of HL-60 cells

Novel vitamin D3 derivatives, 26-homo-delta 22-1 alpha,25(S)-dihydroxyvitamin D3 and 26-homo-delta 22-1 alpha,25(R)-dihydroxyvitamin D3 were compared with the native hormone, 1,25-dihydroxyvitamin D3, and with other vitamin D3 derivatives, in inhibition of cell growth, induction of phenotypic differentiation, and c-myc mRNA reduction of HL-60 cells. The degree of inhibition in cell growth caused by 26-homo-delta 22-1 alpha,25(S)-(OH)2D3 was the greatest followed by 26-homo-delta 22-1 alpha,25(R)-(OH)2D3. The ability to reduce NBT was parallel to that to inhibit cellular proliferation. 26-homo-delta 22-1 alpha,25(S)-(OH)2D3, 26-homo-delta 22-1 alpha,25(R)-(OH)2D3, 24-homo-24-F2-1 alpha,25-(OH)2D3, and 1 alpha,24(R)-(OH)2-26-Cl-D3 were more active than 1 alpha,25-(OH)2D3 in the induction of OK-M1+ and OK-Mo-2+ HL-60 cells. Using two color flow cytometric analysis, the percentages of OK-M5(+)- and OK-DR(+)-HL-60 cells were 33% in the treatment with 26-homo-delta 22-1 alpha,25(S)-(OH)2D3 plus interferon-gamma (IFN-gamma) but 14% in the treatment with 1 alpha,25-(OH)2D3 plus IFN-gamma. 26-Homo-delta 22-1 alpha,25(S)-(OH)2D3 has an inhibitory effect on c-myc reduction in treated HL-60 cells. These results suggest that the novel vitamin D3 derivatives, 26-homo-delta 22-1 alpha,25(S)-(OH)2D3 and 26-homo-delta 22-1 alpha,25(R)-(OH)2D3, have preferential activity in inducing phenotypic differentiation and in inducing cell proliferation related c-myc mRNA activity.

Synthesis of 26,26,26,27,27,27-hexafluoro-25-hydroxyvitamin D3

In order to investigate the biological significance of 26-hydroxylation of vitamin D3, 26,26,26,27,27,27-hexafluoro-25-hydroxyvitamin D3 was prepared from 24-tosyloxy-25,26,27-trinorcholest-5-en-3β-yl tetrahydropyranyl ether.

Chemoenzymatic synthesis of 1α,24(R)-dihydroxycholesterol

Abstract 1α,24( R )-Dihydroxycholesterol, which is the key intermediate for the synthesis of 1α,24( R )-dihydroxyvitamin D 3 , was effectively synthesized via stereoselective esterification of the 24( R )-hydroxy group using a lipase in combination with inversion of configuration of the 24( S )-hydroxy group using the Mitsunobu reaction ( R : S =99:1).

Synthesis and biological evaluation of 1α, 24-dihydroxy-25-nitrovitamin D3

Abstract 1 α ,24( R )-Dihydroxy-25-nitrovitamin D 3 1 and 1 α ,24( S )-dihydroxy-25-nitrovitamin D 3 2 were synthesized using the palladium-catalyzed alkylative enyne cyclization reaction. Their biological properties were studied based on VDR binding affinity and HL-60 cell differentiation activity.