Synthesis and Biological Evaluation of Dichlorinated Chondramide Derivatives

Abstract

Straightforward synthetic protocols for the synthesis of new ethyl‐substituted dichlorinated chondramides with different methyl‐substitution patterns in the polyketide fragment have been developed. The methyl groups at the ϵ‐position can be removed completely without a significant influence on the biological activity. In contrast, after removal of the α‐methyl group, a significant drop in activity is observed. This is also observed if the configuration of the α‐methyl group is inverted.

Synthesis and Late-Stage Modification of (−)-Doliculide Derivatives Using Matteson’s Homologation Approach

“…As our group is experienced in the syntheses of such peptide-polyketide conjugates [23][24][25][26], this assumption led us to develop a straightforward synthesis of doliculide, and associated derivatives, based on Matteson homologation [27][28][29], allowing late-stage variation at exactly this position [30]. In an initial modification, it was demonstrated that replacing the isopropyl group by the smaller methyl group led to almost no change in its cytotoxic activity.…”

Synthesis of modified miuraenamides – the Ugi approach

“…Concerning our ongoing interest into the syntheses of biological active natural products [25][26][27][28][29][30] we also focused on the synthesis of chondramide derivatives 31,32 and we developed a straightforward protocol towards the miuraenamides 33 based on a late stage modification approach. 34 This concept allowed the synthesis of a small library of miuraenamide derivatives via aldol reaction at the C-terminal position of a glycine containing cyclodepsipeptide (Scheme 1).…”

Synthesis and Biological Evaluation of Modified Miuraenamides

“…During our previous studies on the closely related chondramides, we observed that incorporation of halogens into the C ‐terminal aromatic amino acid had a positive effect on the biological activity of these compounds, so we decided to investigate the influence of halogens on the aryl ketone also in this case (Table ). Although one might expect a higher reactivity of the halogenated benzaldehydes, we observed a significantly slower reaction.…”