4,4-Difluoro-1α,25-dihydroxyvitamin D3: Analog to probe A-ring conformation in vitamin D-receptor complex

Tetrahedron Letters

Volumn 40, Issue 9, 1999, Pages 1697-1700

  Shimizu, Masato ^a   Iwasaki, Yukiko ^a   Yamada, Sachiko ^a  

^a TOKYO MEDICAL AND DENTAL UNIVERSITY   (Japan)

Author keywords

Conformation; Fluorine and compounds; NMR; Vitamins

Indexed keywords

4,4 DIFLURO 1ALPHA,25 DIHYDROXYVITAMIN D3; CALCITRIOL RECEPTOR; UNCLASSIFIED DRUG; VITAMIN D RECEPTOR;

ARTICLE; DRUG RECEPTOR BINDING; MOLECULAR INTERACTION; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PROTEIN CONFORMATION; STRUCTURE ANALYSIS;

EID: 0033605271     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(99)00030-1     Document Type: Article

References (19)

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12. + 17); 434 (34); 323 (56); 305 (18); 135 (100). UV λmax (95 % EtOH): 271 nm.
13. 19F NMR spectra of 2 and 3 were assigned on the basis of the spectra of rigid difluorosteroid derivatives 5 - 8: In the spectra of 5 and 6, which have both an α-OH group and an α-double bond, the fluorine signals appear in the following order of increasing shielding: (1) axial F with an anri-parallel OH and a parallel π-bond orbital (-82.6), (2) axial with a cis-OH and a parallel π-bond orbital (-98.1 ), (3) equatorial with a cis-OR and an orthogonal π-orbital (-115.0), and (4) equatorial with a trans-OH and an orthogonal π-orbital (-116.5), while in the spectra of 7 and 8, which have only an α-OH group, the order is: (1) equatorial F with a cis-OH (-106.9), (2) equatorial with a trans-OH (-108.5), (3) axial with an anri-parallel α-OH (-112.1), and (4) axial with a cis-OH (-126.4). Thus, the signals in the spectra shown in Fig. 1b can be assigned as follows: the lowest signal (-92.9) to 4α-F and its partner (-119.8) to 4β-F in the β-form; the highest signal (-121.2) to 4α-F and its partner (-108.1) to4β-F in the α-form: a) Bovey FA, Anderson EW, Hood FP, Kornegay RL. J. Chem. Phys. 1964;40:3099-3109;
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