Synthesis and Biological Evaluation of C(13)/C(13')-Bis(desmethyl)disorazoleâ
Z.
Angew Chem Int Ed Engl
; 62(5): e202212190, 2023 01 26.
Article
in En
| MEDLINE
| ID: mdl-36281761
ABSTRACT
We describe the total synthesis of the macrodiolide C(13)/C(13')-bis(desmethyl)disorazoleâ
Z through double inter-/intramolecular Stille cross-coupling of a monomeric vinyl stannane/vinyl iodide precursor to form the macrocycle. The key step in the synthesis of this precursor was a stereoselective aldol reaction of a formal Evans acetate aldol product with crotonaldehyde. As demonstrated by X-ray crystallography, the binding mode of C(13)/C(13')-bis(desmethyl)disorazoleâ
Z to tubulin is virtually identical with that of the natural product disorazoleâ
Z. Likewise, C(13)/C(13')-bis(desmethyl)disorazoleâ
Z inhibits tubulin assembly with at least the same potency as disorazoleâ
Z and it appears to be a more potent cell growth inhibitor.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tubulin
/
Macrolides
Language:
En
Journal:
Angew Chem Int Ed Engl
Year:
2023
Document type:
Article
Affiliation country:
Switzerland