The novel 19 nor l α ,25 dihydroxy vitamin D 3 analogues possessing an ethyl at the 2 position(4 and 5), were synthesized by coupling 25 hydroxy Windaus Grundmann ketone derivative 20 with A ring syntho...The novel 19 nor l α ,25 dihydroxy vitamin D 3 analogues possessing an ethyl at the 2 position(4 and 5), were synthesized by coupling 25 hydroxy Windaus Grundmann ketone derivative 20 with A ring synthons(15 and 19) respectively. The enantioselective synthesis of substituted bicyclic hexanes structure A ring synthons, started from all cis 3,5 dihydroxy 4 ethyl 1 (methoxycarbonyl)cyclohexane via lipase catalyzd asymmetrization, was demonstrated.展开更多
Synthesis of an optically active intermediate 4b for the A-ring of 1a,25-dihydroxyvitamin D3 analogs has been achieved in eight steps, starting from readily available, inexpensive D-(+)-xylose.
The synthesis of 14-epi-19-nor-22-oxa-1α,25（OH）2D3 5 was started from diol 8 via Fall＇s method, oxidation, epimerization, protection, coupling with the 19-nor-A-ring 7, and then deprotection of the hydroxyl functi...The synthesis of 14-epi-19-nor-22-oxa-1α,25（OH）2D3 5 was started from diol 8 via Fall＇s method, oxidation, epimerization, protection, coupling with the 19-nor-A-ring 7, and then deprotection of the hydroxyl functions.展开更多
Nor-1α, 25-dihydroxy-22-oxo-vitamin D3 4 was synthesized by the coupling of known compound 5 and the A-ring phosphine oxide 6 followed by deprotection of the hydroxy functions.
An optically active intermediate 5 for A-ring of 19-nor-1α,25-dihydroxyvitamin D3 2 has been synthesized in five steps, starting from readily available, inexpensive v（＋）-xylose 6 with good yield.
Our previous studies revealed that 1, 25-dihydroxyvrtamin D_3[1, 25 (OH)_2, D_3] and its two novel analogues (MC903 and EB1089) play an important role in the modulation of proliferation and differentiation of a newly ...Our previous studies revealed that 1, 25-dihydroxyvrtamin D_3[1, 25 (OH)_2, D_3] and its two novel analogues (MC903 and EB1089) play an important role in the modulation of proliferation and differentiation of a newly established human megakaryoblastic leu展开更多
AIM： To investigate the possible involvement of 25-hydroxyvitamin D3-1cx-hydroxylase [1α-25（OH）2D3] in butyrate-induced differentiation in human intestinal cell line Caco-2 cells. METHODS： Caco-2 cells were incub...AIM： To investigate the possible involvement of 25-hydroxyvitamin D3-1cx-hydroxylase [1α-25（OH）2D3] in butyrate-induced differentiation in human intestinal cell line Caco-2 cells. METHODS： Caco-2 cells were incubated either with 3 mmol/L butyrate and 1 umol/L 25（OH）2D3 or with 1 umol/L 1α-25（OH）2D3 for various time intervals ranging from 0 to 72 h. Additionally, cells were co-incubated with butyrate and either 25（OH）2D3 or 1α-25（OH）2D3. 1α-25（OH）2D3 mRNA was determined semi-quantitatively using the fluorescent dye PicoGreen. Immunoblotting was used for the detection of 1α-25（OH）2D3 protein. Finally, enzymatic activity was measured by ELISA. RESULTS： Both butyrate and 1α-25（OH）2D3 stimulated differentiation of Caco-2 cells after a 48 h incubation period, while 25（OH）2D3 had no impact on cell differentiation. Synergistic effects on differentiation were observed when cells were co-incubated with butyrate and vitamin D metabolite. Butyrate transiently upregulated 1α-25（OH）2D3 mRNA followed by a timely delayed protein upregulation. Coincidently, enzymatic activity was enhanced significantly. The induction of the enzyme allowed for comparable differentiating effects of both vitamin D metabolites. CONCLUSION： Our experimental data provide a further mechanism for the involvement of the vitamin D signaling pathway in colonic epithelial cell differentiation by butyrate. The enhancement of 1α-25（OH）2D3 followed by antiproliferative effects of the vitamin D prohormone in the Caco-2 cell line suggest that 25（OH）2D3 in combination with butyrate may offer a new therapeutic approach forthe treatment of colon cancer.展开更多
文摘The novel 19 nor l α ,25 dihydroxy vitamin D 3 analogues possessing an ethyl at the 2 position(4 and 5), were synthesized by coupling 25 hydroxy Windaus Grundmann ketone derivative 20 with A ring synthons(15 and 19) respectively. The enantioselective synthesis of substituted bicyclic hexanes structure A ring synthons, started from all cis 3,5 dihydroxy 4 ethyl 1 (methoxycarbonyl)cyclohexane via lipase catalyzd asymmetrization, was demonstrated.
文摘Synthesis of an optically active intermediate 4b for the A-ring of 1a,25-dihydroxyvitamin D3 analogs has been achieved in eight steps, starting from readily available, inexpensive D-(+)-xylose.
文摘The synthesis of 14-epi-19-nor-22-oxa-1α,25（OH）2D3 5 was started from diol 8 via Fall＇s method, oxidation, epimerization, protection, coupling with the 19-nor-A-ring 7, and then deprotection of the hydroxyl functions.
基金Financial support from the National Natural Science foundation of China (No: 29972013) is gratefully acknowledged.
文摘Nor-1α, 25-dihydroxy-22-oxo-vitamin D3 4 was synthesized by the coupling of known compound 5 and the A-ring phosphine oxide 6 followed by deprotection of the hydroxy functions.
基金Financial support from the National Natural Science Foundation of China(No.29972013)is gratefully acknowledged.
文摘An optically active intermediate 5 for A-ring of 19-nor-1α,25-dihydroxyvitamin D3 2 has been synthesized in five steps, starting from readily available, inexpensive v（＋）-xylose 6 with good yield.
文摘Our previous studies revealed that 1, 25-dihydroxyvrtamin D_3[1, 25 (OH)_2, D_3] and its two novel analogues (MC903 and EB1089) play an important role in the modulation of proliferation and differentiation of a newly established human megakaryoblastic leu
基金Supported by the Else Kroner-Fresenius Foundation, Bad Homburg, Germany
文摘AIM： To investigate the possible involvement of 25-hydroxyvitamin D3-1cx-hydroxylase [1α-25（OH）2D3] in butyrate-induced differentiation in human intestinal cell line Caco-2 cells. METHODS： Caco-2 cells were incubated either with 3 mmol/L butyrate and 1 umol/L 25（OH）2D3 or with 1 umol/L 1α-25（OH）2D3 for various time intervals ranging from 0 to 72 h. Additionally, cells were co-incubated with butyrate and either 25（OH）2D3 or 1α-25（OH）2D3. 1α-25（OH）2D3 mRNA was determined semi-quantitatively using the fluorescent dye PicoGreen. Immunoblotting was used for the detection of 1α-25（OH）2D3 protein. Finally, enzymatic activity was measured by ELISA. RESULTS： Both butyrate and 1α-25（OH）2D3 stimulated differentiation of Caco-2 cells after a 48 h incubation period, while 25（OH）2D3 had no impact on cell differentiation. Synergistic effects on differentiation were observed when cells were co-incubated with butyrate and vitamin D metabolite. Butyrate transiently upregulated 1α-25（OH）2D3 mRNA followed by a timely delayed protein upregulation. Coincidently, enzymatic activity was enhanced significantly. The induction of the enzyme allowed for comparable differentiating effects of both vitamin D metabolites. CONCLUSION： Our experimental data provide a further mechanism for the involvement of the vitamin D signaling pathway in colonic epithelial cell differentiation by butyrate. The enhancement of 1α-25（OH）2D3 followed by antiproliferative effects of the vitamin D prohormone in the Caco-2 cell line suggest that 25（OH）2D3 in combination with butyrate may offer a new therapeutic approach forthe treatment of colon cancer.
