Enantio- and Diastereoselective Organocatalytic α-Alkylation of Aldehydes with 3-Substituted 2-(Bromomethyl)acrylates

The catalytic direct α-alkylation of aldehydes with 2-(bromomethyl)­acrylates has been accomplished, giving rise to α-branched and functionalized aldehydes of high diastereo- and enantiopurity. The influence of the nature of the ester group of the acrylates in reaction stereoselectivity and especially in reactivity is investigated. Optimum conditions implicate the use of phenyl acrylates in conjunction with organocatalyst <b>8</b>. Application of thus obtained adducts in synthesis is illustrated with a concise stereocontrolled preparation of trisubstituted cyclopentenes

Enantio- and Diastereoselective Organocatalytic α-Alkylation of Aldehydes with 3-Substituted 2-(Bromomethyl)acrylates

The catalytic direct α-alkylation of aldehydes with 2-(bromomethyl)­acrylates has been accomplished, giving rise to α-branched and functionalized aldehydes of high diastereo- and enantiopurity. The influence of the nature of the ester group of the acrylates in reaction stereoselectivity and especially in reactivity is investigated. Optimum conditions implicate the use of phenyl acrylates in conjunction with organocatalyst <b>8</b>. Application of thus obtained adducts in synthesis is illustrated with a concise stereocontrolled preparation of trisubstituted cyclopentenes

Synthesis and Biological Evaluation of 1α,25-Dihydroxyvitamin D₃ Analogues with a Long Side Chain at C12 and Short C17 Side Chains

Structure-guided optimization was used to design new analogues of 1α,25-dihydroxyvitamin D₃ bearing the main side chain at C12 and a shorter second hydroxylated chain at C17. The new compounds <b>5a</b>–<b>c</b> were efficiently synthesized from ketone <b>9</b> (which is readily accessible from the Inhoffen–Lythgoe diol) with overall yields of 15%, 6%, and 3% for <b>5a</b>, <b>5b</b>, and <b>5c</b>, respectively. The triene system was introduced by the Pd-catalyzed tandem cyclization–Suzuki coupling method. The new analogues were assayed against human colon and breast cancer cell lines and in mice. All new vitamin D₃ analogues bound less strongly to the VDR than 1α,25-dihydroxyvitamin D₃ but had similar antiproliferative, pro-differentiating, and transcriptional activity as the native hormone. In vivo, the three analogues had markedly low calcemic effects