Concise Synthesis of Tunicamycinâ
V and Discovery of a Cytostatic DPAGT1 Inhibitor.
Angew Chem Int Ed Engl
; 61(31): e202203225, 2022 08 01.
Article
in En
| MEDLINE
| ID: mdl-35594368
ABSTRACT
A short total synthesis of tunicamycinâ
V (1), a non-selective phosphotransferase inhibitor, is achieved via a Büchner-Curtius-Schlotterbeck type reaction. Tunicamycinâ
V can be synthesized in 15 chemical steps from D-galactal with 21 % overall yield. The established synthetic scheme is operationally very simple and flexible to introduce building blocks of interest. The inhibitory activity of one of the designed analogues 28 against human dolichyl-phosphate N-acetylglucosaminephosphotransferase 1 (DPAGT1) is 12.5â
times greater than 1. While tunicamycins are cytotoxic molecules with a low selectivity, the novel analogue 28 displays selective cytostatic activity against breast cancer cell lines including a triple-negative breast cancer.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cytostatic Agents
/
Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
Angew Chem Int Ed Engl
Year:
2022
Document type:
Article
Affiliation country:
Estados Unidos