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

Abstract

Three novel 19‐nor‐1α,25‐dihydroxyvitamin D3 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.

Julia‐Kocienski Olefination in the Synthesis of Trisubstituted Alkenes: Recent Progress

“…BT‐sulfone 263 reacted separately with cyclohexanones 266 a and 266 b in the presence of LiHMDS at −78 °C in THF to obtain the desired trisubstituted olefins 267 a , 267 b each as a 1 : 1 diastereomeric mixture (92 % and 71 % yields, respectively). In search for novel vitamin D derivatives of potential therapeutic value and following a similar strategy, Ferrero et al [108] . utilized BT‐derivative 265 a as the sulfone partner.…”