Synthesis and conformation of four 16,17-diols in the 3-methoxy-13alpha-estra-1,3,5(10)-triene series.
All four diasteromeric 16,17-diols in the 3-methoxy-13alpha-estra-1,3,5(10)-triene series have been synthesized. The trans-diols 1 and 2 can be obtained by hydroborating the 17-enol acetate 6 (61%, ratio 27:73, preferred alpha attack). OsO(4) dihydroxylation of the olefin 7 yielded the cis-diols 3 and 4 (ratio 13:87). The dihydroxylation proceeds with preference for beta attack caused by a C-ring twist-boat form of 7. The conformations of the diols 2 and 4, the 17-benzyl-17-hydroxy compounds 9 and 10 (obtained by Grignard reaction), and the 16alpha-bromo-17beta-hydroxy compound 8 were determined by X-ray analysis and by 1H NMR spectroscopy in solution. Some compounds, in spite of a 17beta-hydroxy group, had a conformation with a ring C chair form (4, 8, 9) caused by intermolecular interaction in the solid state. The rest of the compounds studied here (2, 10) possessed a conformation with a ring C twist-boat form, which has been also found for all 17beta-substituted compounds in solution. The preferred conformation of the D-ring with 17beta-substituents seems to be the 16beta-envelope form or near this form, but the existence of the 16alpha-envelope form (inversion of the ring D) for some compounds showed great variance in the conformation of ring D, which is substituent dependent.
Schwarz
Sigfrid
S
Jenapharm GmbH & Co. KG, Otto-Schott-Str. 15, D-07745 Jena, Germany.
Schönecker
Bruno
B
Fritsche
Kai
K
Poser
Andreas
A
Lange
Corinna
C
Günther
Wolfgang
W
Göttke
Stephan
S
Görls
Helmar
H
Bäsler
Siegfried
S
D004963:Estrenes / Q000138:chemical synthesis* / Q000737:chemistry*; D006860:Hydrogen Bonding; D007536:Isomerism; D008958:Models, Molecular; D008968:Molecular Conformation; D012996:Solutions; D014961:X-Ray Diffraction
D004963:Estrenes; D012996:Solutions; C015347:3-methoxyestra-1,3,5(10)-triene