19-Methyl Analogs of Vitamin D_3:Synthesis and Structure Elucidation by ~1H NMR

摘要

Synthesis of three isomeric 19-methylated vitamin D_3 derivatives is described.Two different synthetic paths were used,both involving 3,5-cyclovitamin D precursors easily obtainable from commercial vitamin D_3.The crucial step of the first route consisted of an acid-catalyzed cycloreversion of isomeric 19-methyl-3,5-cyclovitamin D_3 compounds,whereas in the other it involved a Wittig reaction of 10-oxo-19-norvitamin analogs.Neither iodine-catalyzed nor thermal isomerization of the 5Z,10￡-isomer provided detectable quantities of the fourth possible isomeric vitamin with a 5Z,10Z-configuration.Structures,stereochemistries and A-ring conformations of the final 19-methyl vitamin D_3 analogs were tentatively established on the basis of their 500-MHz ~1H NMR spectra and conformational analysis.Application of ~1H NOE difference spectroscopy and molecular modeling studies allowed for the assignment of preferred solution conformations of the 3,5-cyclovitamin D_3 intermediates.