Projects per year
Abstract
Duocarmycins are highly potent and promising anticancer payloads for ADC applications. They tolerate a range of chemical modifications which allow the chemist to modulate both their biophysical and pharmacological properties. The possibility to synthesize these payloads on resin and orthogonally add linkers while immobilized on the solid phase, would allow a combinatorial design of payload analogues with linkers, potentially aided by automation. Working towards this goal, we report a concise and high yielding synthesis of an alkylating unit suitable for solid phase synthesis (10, 9 steps, 34% yield) and demonstrate its applicability to the synthesis of duocarmycin SA analogues (19, 20). An intermediate for traditional solution phase synthesis (8) is also described in 7 steps and 44% yield. A side reaction with potential application to the stereoselective synthesis of these derivatives has also been described.
Original language | English |
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Article number | 153058 |
Journal | Tetrahedron Letters |
Volume | 72 |
Early online date | 6 Apr 2021 |
DOIs | |
Publication status | Published - 25 May 2021 |
Keywords
- Antibody drug conjugate
- Duocarmycin
- Natural product
- Solid phase
- Yatakemycin
Projects
- 1 Finished
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Anti tumour agents from natural products - new approaches to targeting ultra potent analogues of the duocarmycins.
Searcey, M., O'Connell, M. & Cominetti, M.
Engineering and Physical Sciences Research Council
1/01/20 → 31/08/23
Project: Research