Total Synthesis of Marine Cyclic Enol-Phosphotriester Salinipostin Compounds

The Chemistry and Biology of Cyclophostin, the Cyclipostins and Related Compounds

“…Tao and coworkers reported the synthesis of six racemic salinipostins ( 4 ) and their diastereoisomers ( 14 ) (Scheme 1 and Scheme 2) [19]. They adopted the chemistry developed by Spilling et al [11] for the synthesis of cyclophostin and the cyclipostins, substituting various carboxylic anhydrides for acetic anhydride to introduce the enol phosphate alkyl substituents (R 1 ) required for the salinipostins.…”

Cyclipostins and Cyclophostin Analogues as Multitarget Inhibitors That Impair Growth of Mycobacterium abscessus

“…CyC19 to CyC30, by varying the lipophilicity of the R 3 chain located on the 7-membered enolphosphorus ring in our phosphate and phosphonate analogs. This structural modification is also supported by the isolation of the anti-malarial Salinipostins, [33][34] which are essentially Cyclipostins with variations in the enol alkyl substituent.…”

“…Herein, we have synthesized 12 new analogues, i.e., CyC 19 to CyC 30 , by varying the lipophilicity of the R 3 chain located on the 7-membered enolphosphorus ring in our phosphate and phosphonate analogues. This structural modification is also supported by the isolation of the antimalarial Salinipostins, 33,34 which are essentially Cyclipostins with variations in the enol alkyl substituent. Their respective antibacterial activity was further assessed against a panel of pathogenic mycobacteria, including the M. abscessus R and S variants.…”

The phosphate ester group in secondary metabolites

“…Salinipostins A-K ( 109–119 ) displayed potent antimalarial and cytotoxic activity, with 109 showing EC 50 = 50 nM against P. falciparum and EC 50 = 50 mM for HEK 293 T. The syntheses of racemic 109 , 110 , 114 , 115 , 117 and 118 have been accomplished as well as the corresponding stereoisomers bearing the same relative configuration as those observed for cyclophostins (see Section 4). 212…”