Convergent Approaches and Biological Activity of C1 and/or C3 Mono or Diamino Derivatives of 1α,25-Dihydroxy-19-nor-vitamin D3. Key Enzymatic Desymmetrization of A-Ring Synthon Precursor

Three novel 19-nor-1 alpha,25-dihydroxyvitamin D-3 derivatives modified at C1 and/or C3 with an amino group were synthesized to study the influence of the substitution of one or both hydroxyl groups of A-ring by amino groups on the affinity for vitamin D receptor (VDR) and vitamin D binding protein (hDBP), and also on the antiproliferative activity. The A-ring precursors were prepared from cis,cis-1,3,5-cyclohexanetriol applying a desymmetrization reaction of a prochiral 1,3-diol catalyzed by Pseudomonas cepacia lipase as a key step. The structural elucidation of diastereoisomers were unambiguously assigned by NMR spectroscopy.

Automated summary

Three novel 19-nor-1 alpha,25-dihydroxyvitamin D-3 derivatives modified at C1 and/or C3 with an amino group were synthesized to investigate the impact of substituting one or both hydroxyl groups of the A-ring with amino groups on the affinity for VDR and hDBP, as well as the antiproliferative activity. The A-ring precursors were obtained through a desymmetrization reaction of a prochiral 1,3-diol catalyzed by Pseudomonas cepacia lipase, and the diastereoisomers were identified by NMR spectroscopy.