Solid-phase synthesis of macrolide analogues.
The synthesis of a solid-phase macrolide library is described. The library introduces three sites of diversity to a suitable macrolide scaffold via reductive aminations.
Azithromycin↗
Biomedical subjects
T J Sowin
Publications and source records attributed to T J Sowin.
Solid-phase synthesis of benzoxazoles from 3-nitrotyrosine.
A method to synthesize benzoxazoles on solid phase using 3-nitrotyrosine as a scaffold has been developed. The synthesis couples N-protected 3-nitrotyrosine to polystyrene via a Wang-type linker. The polymer-supported 3-nitrotyrosine is deprotected and the resultant primary amine converted to a tertiary amine via sequential reductive alkylation using aromatic followed by unhindered aliphatic aldehydes. The phenol is acylated, and the nitro group is reduced using SnCl(2). The resulting amino ester is then dehydratively cyclized to a benzoxazole. The synthesis was developed for a large mix and split (50 x 50 x 50) combinatorial library. The single compounds presented herein represent a diverse array of the types of monomers amenable to the chemistry developed.
Alkylation↗
Application of base cleavable safety catch linkers to solid phase library production.
We have used sulfide "Safety Catch" linkers to anchor typical medicinal chemistry functional groups to amine resins. Compounds are loaded as the ester, carbamate, or amine. At the end of the synthesis, the linker is activated by peracid. The sulfone resins are then cleaved by beta-elimination in the gas phase or in solution by secondary amines to produce acids and primary, secondary, or tertiary amines. Comparison of cleavage rates to other sulfone resins including SEM showed significantly faster cleavage for this system with conditions similar to Fmoc deprotection. Application of this strategy to a medicinal chemistry library gives good yields and purities of the resulting compounds.
Chemistry, Pharmaceutical↗