Solid-phase asymmetric synthesis using a polymer-supported chiral Evans'-type oxazolidin-2-one

Abstract

This protocol describes the synthesis of (S)-4-(4-hydroxybenzyl)-oxazolidin-2-one, its attachment to a Merrifield-Cl resin and its use for asymmetric synthesis. The chiral auxiliary is prepared in four steps from N-Boc-L-tyrosine on a multigram scale in high yield and attached to Merrifield-Cl resin via its phenolic group to afford a solid-supported chiral auxiliary for asymmetric synthesis that takes ∼7 d to prepare. A procedure for its N-acylation is reported and a method for carrying out diastereoselective solid-supported Evans' syn-aldol reactions is described, with aldol products being cleaved from the polymer by either hydrolysis or reduction. The use of the supported auxiliary for two sequential 'on-bead' reactions has been demonstrated for the synthesis of a chiral cyclopropane aldol and a γ-lactone in a >95:5 diastereomeric ratio. These polymer-supported reactions are carried out in IRORI Kan resin capsules to protect the polymer support from mechanical degradation, thus allowing multiple on-bead reactions to be performed.

Size-Reduced Macrocyclic Analogues of [Pyr1]-apelin-13 Showing Negative Gα12 Bias Still Produce Prolonged Cardiac Effects

“…For compound 1 , allylglycine residues were introduced at both positions to prepare for cyclization using ring-closing metathesis (RCM) (Scheme ). Compound 2 was obtained from 1 by hydrogenation using 10% Pd/C catalyst . Compounds 3 and 6 were synthesized by macrolactamization according to the protocol described previously, with Dap­(Alloc) or Lys­(Alloc) in Pro3 position and Asp­(OAll) in His7 position, respectively.…”

“…Compound 2 was obtained from 1 by hydrogenation using 10% Pd/C catalyst. 65 Compounds 3 and 6 were synthesized by macrolactamization according to the protocol described previously, 66 with Dap(Alloc) or Lys-(Alloc) in Pro3 position and Asp(OAll) in His7 position, respectively. Macrocycles 4, 5, 7, and 8 were also prepared using RCM (Scheme 1).…”

Synthesis of optically pure ant pheromones with high enantiomeric purity.

“…Over the last few decades there has been much interest in the development of polymersupported chiral auxiliaries as an expedient and clean method for producing libraries of chiral compounds [2]. The major benefit of this approach is rapid and simplified purification of reaction by filtration, allowing for simple isolation of the desired chiral products and facile recovery of the polymersupported auxiliaries [3]. A number of polymer-supported auxiliaries have been developed for asymmetric synthesis, with recent examples using auxiliaries derived from ephedrine [4,5], pseudo ephedrine [6], sugars [7,8], hydrobenzoin [9,10], sulfoxide and sulfinamides [11], sulfoximine [12], naphthamide [13], hydroxyl pyrolidinone [14], imidazolidinone [15], and hydrazones [16].…”