Pharmacophore-directed retrosynthesis applied to ophiobolin A led to bicyclic derivatives that were synthesized and display anticancer activity. Key features of the ultimate defensive synthetic strategy include a Michael addition/facially selective protonation sequence to set the critical C6 stereocenter and a ring-closing metathesis to form the cyclooctene. Cytotoxicity assays toward a breast cancer cell line (MDA-MB-231) confirm the anticipated importance of structural complexity for selectivity (vs MCF10A cells) while C3 variations modulate stability.
Pharmacophore-Directed Retrosynthesis Applied to Ophiobolin A: Simplified Bicyclic Derivatives Displaying Anticancer Activity / Tao, Y.; Reisenauer, K. N.; Masi, M.; Evidente, A.; Taube, J. H.; Romo, D.. - In: ORGANIC LETTERS. - ISSN 1523-7060. - 22:21(2020), pp. 8307-8312. [10.1021/acs.orglett.0c02938]
Pharmacophore-Directed Retrosynthesis Applied to Ophiobolin A: Simplified Bicyclic Derivatives Displaying Anticancer Activity
Masi M.Writing – Original Draft Preparation
;Evidente A.Writing – Review & Editing
;
2020
Abstract
Pharmacophore-directed retrosynthesis applied to ophiobolin A led to bicyclic derivatives that were synthesized and display anticancer activity. Key features of the ultimate defensive synthetic strategy include a Michael addition/facially selective protonation sequence to set the critical C6 stereocenter and a ring-closing metathesis to form the cyclooctene. Cytotoxicity assays toward a breast cancer cell line (MDA-MB-231) confirm the anticipated importance of structural complexity for selectivity (vs MCF10A cells) while C3 variations modulate stability.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
