66791-71-7Relevant articles and documents
Synthesis and biological activities of 2α-chloro-1-epicalcitriol and 1- epicalcitriol
Schoenecker, Bruno,Reichenbaecher, Manfred,Gliesing, Sabine,Gonschior, Manuela,Griebenow, Sirid,Scheddin, Dietmar,Mayer, Hubert
, p. 28 - 36 (1998)
Anomalous diequatorial epoxide ring opening of 1β, 2β-oxido-cholesta- 5,7-diene-3β,25-diol 1 produces the 1β-hydroxy-2α-chloro-provitamin 2 and its corresponding 1β-hydroxy-provitamin 3. The provitamins 2 and 3 are transformed by irradiation and thermal isomerization to 2α-chloro-1- epicalcitriol NS3 (4) and 1-epicalcitriol NS8 (5), respectively. These two A- ring derivatives were tested for their in vitro biological activity in the mesenchymal, murine cell line C3H10T 1/4 , and their effects were compared with those of the native vitamin D3 derivatives 25(OH)D3 and 1,25(OH)2D3. NS3 and NS8 showed marked differences in their affinity for the vitamin D binding protein (DBP) and in their ability to inhibit cell proliferation. NS8 has the ability to bind to a high-affinity DBP-binding site for which 25(OH)D3 has none affinity. The 2α-chloro-substitution (NS3) prevents binding to the postulated noncompetitive, NS8-specific DBP-binding site and diminishes the affinity to the vitamin D receptor (VDR) and therefore diminishing NS3 's biological abilities. The elucidation of the structure-function relationships at the DBP-binding-sites could have major impact on the development of new vitamin D3 derivatives with extended serum half-life.
New Convergent Synthesis of 1α,25-Dihydroxyvitamin D3 and Its Analogues by Suzuki-Miyaura Coupling between A-Ring and C,D-Ring Parts
Hanazawa, Takeshi,Koyama, Akiko,Nakata, Kunio,Okamoto, Sentaro,Sato, Fumie
, p. 9767 - 9772 (2007/10/03)
A new convergent method for the synthesis of 1α,25 -dihydroxyvitamin D3 and its analogues has been developed that involves efficient preparation of the A-ring part 1a, (Z)-(3S,5R)-1-bromom-ethylene-3,5-bis(tert-butyldimethylsilyloxy) -2-methylenecyclohexane, starting from epichlorohydrin (4) and its Suzuki-Miyaura coupling reaction with the C,D-ring part 12. Thus, (R)-4 was converted to (3S,5R)-5-(tert-butyldimethylsilyloxy)-8-(trimethylsilyl)-oct-l-en-7-yn-3-ol (3a) through a ten-step reaction sequence in 49% overall yield. Compound 3a thus obtained was treated with a Ti(O-i-Pr)4/2 i-PrMgCl reagent and then with NBS to afford (Z)-(1S,2S,5R)-2-bromomethyl-3-[bromo-(trimethylsilyl)methylene] -5-(tert-butyldimethylsilyloxy)cyclohexanol (10a) in 51% yield, from which la was obtained in 87% yield by sequential treatment with TBSCl/imidazole, DBU, and Cs2CO3. The resulting A-ring intermediate 1a was reacted with alkenylboronate 12 in the presence of a PdCl2(dppf) catalyst to furnish 1α,25 -dihydroxyvitamin D3 in 82% yield after protodesilylation. Similarly, all of the other three possible stereoisomers of A-ring parts 1b, 1c, and 1d were prepared, from which 1-epi-, 3-epi-, and 1,3-di-epi-1α,25-dihydroxyvitamin D3 were synthesized by coupling with 12 in excellent yield, respectively. Starting from 1a and 1c, des-C,D-1α,25-dihydroxyvitamin D3 analogues, retiferol 13 and its 3-epi derivative, were also prepared, respectively.
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.
