203126-84-5Relevant academic research and scientific papers
Systematic studies on synthesis, structural elucidation, and biological evaluation of A-ring diastereomers of 2-methyl-1α,25-dihydroxyvitamin D3 and 20-epi-2-methyl-1α,25-dihydroxyvitamin D3
Takayama, Hiroaki,Konno, Katsuhiro,Fujishima, Toshie,Maki, Shojiro,Liu, Zhaopeng,Miura, Daishiro,Chokki, Manabu,Ishizuka, Seiichi,Smith, Connie,DeLuca, Hector F.,Nakagawa, Kimie,Kurobe, Mayuko,Okano, Toshio
, p. 277 - 285 (2007/10/03)
All possible A-ring diastereomers of 2-methyl-1α,25-dihydroxyvitamin D3 (2) and 20-epi-2-methyl-1α,25-dihydroxyvitamin D3 (3) were synthesized by palladium-catalyzed coupling reaction of A-ring 'enyne' synthons with CD-ring portions. The A-ring synthons were rationally synthesized via a novel and practical route, starting with methyl (R)-(+)- and (S)-(-)-3-hydroxy-2-methyl-propionate, in good yields. X-ray crystallographic analysis of 2α-methyl-1α,25-dihydroxyvitamin D3 (2b) and conformational analysis of the A-ring of 2α-methyl-(2b) and 2β-methyl-1α,25-dihydroxyvitamin D3 (2f) were carried out, and the results are described. All A-ring diastereomers (2 and 3), thus synthesized, were biologically evaluated both in vitro and in vivo. The biologic potency was highly dependent on the stereochemistry of the A-ring substituents. In particular, 2b showed 4-fold higher vitamin D receptor [VDR] binding activity than the natural hormone, and its 20-epimer (3b) exhibited exceptionally high activity, 12-fold more potent in VDR binding, 7-fold in calcium mobilization, and 590-fold in induction of human promyelocytic leukemia (HL-60) cell differentiation as compared with the natural hormone. Further, the 20-epi-2β-Me-1β, 3α(OH)2 isomer (3g) had significant biologic potencies compared to the natural hormone despite having 1β-OH configuration. The transcriptional activities on human osteocalcin gene promoter, including VDRE in transfected mammalian cells, were also evaluated. Finally, there was a clear contrast between the effects of the 2-methyl group on the HL-60 cell differentiation- and apoptosis-inducing activities of 2 and 3. Copyright
Synthesis, biological evaluation, and conformational analysis of A-ring diastereomers of 2-methyl-1,25-dihydroxyvitamin D3 and their 20-epimers: Unique activity profiles depending on the stereochemistry of the A-ring and at C-20
Konno,Fujishima,Maki,Liu,Miura,Chokki,Ishizuka,Yamaguchi,Kan,Kurihara,Miyata,Smith,DeLuca,Takayama
, p. 4247 - 4265 (2007/10/03)
All eight possible A-ring diastereomers of 2-methyl-1,25-dihydroxyvitamin D3 (2) and 2-methyl-20-epi-1,25-dihydroxyvitamin D3 (3) were convergently synthesized. The A-ring enyne synthons 19 were synthesized starting with methyl (S)-(
A novel and practical route to A-ring enyne synthon for 1α,25-dihydroxyvitamin D3 analogs: Synthesis of A-ring diastereomert of 1α,25-dihydroxyvitamin D3 and 2-methyl-1,25-dihydroxyvitamin D3
Konno, Katsuhiro,Maki, Shojiro,Fujishima, Toshie,Zhaopeng, Liu,Miura, Daishiro,Chokki, Manabu,Takayama, Hiroaki
, p. 151 - 156 (2007/10/03)
A novel and practical route to the A-ring enyne synthon (2), which can be versatile far a variety of A-ring analogs of 1α,25-dihydroxyvitamin D3 (1), was developed. This novel method led to an improved synthesis of the A-ring diastereomers of 1, the compounds 13-15, and synthesis of the new analogs, 2-methyl-1,25-dihydroxyvitamin D3 (4) with its all possible diastereomers. The biological evaluation of the 2-methyl analogs showed the ααβ-isomer to be more potent than 1.
