A unified synthetic approach to the pyrazinone dragmacidins

Enantioselective Decarboxylative Alkylation Reactions: Catalyst Development, Substrate Scope, and Mechanistic Studies

“…Hydroxy acid 74 has previously been employed in the synthesis of quinic acid ( 75 ), [79] a common chiral pool starting material used in many synthetic efforts, [80] including the total synthesis of dragmacidin F reported by our laboratory. [81] Vinylogous ester 76 is a versatile precursor and can be elaborated to the natural products carissone ( 77 ) [24e] and cassiol ( 78 ). [24f] …”

Syntheses of cyclic guanidine-containing natural products

“…Biosynthetically, 2 and 152 are likely derived from 151 . 34 Notable biological activities of these marine sponge metabolites include selective inhibition of serine-threonine protein phosphatases 1 (PP1) over the 2A isoform (PP2A), 212 brain nitric oxide synthase (bNOS) over the inducible isoform (iNOS), 1 and HIV-1 over HSV virus. 19 …”

Total Synthesis of (±)-Dragmacidin E; Problems Solved and Lessons Learned

“…3 Whereas it is not clear if the pyrazinone group shares any more than formal nomenclatural identity with the piperazine group, it seems more likely that the members of the pyrazinone dragmacidins are biosynthetically related to each other, as first proposed by Capon and Riccio and later discussed in detail by Garg and Stoltz. 1 Thus, formal isomerization of dragmacidin D ( 2 ) with connection of C(5) to C(5‴) would deliver dragmacidin E ( 1 ), and oxidative cyclization within ( 2 ) with attachment of C(4‴) to C(6″) might serve as a blueprint for the biosynthesis of dragmacidin F ( 3 ). Neither of these putative biosynthesis transformations has been realized in vitro, although a large body of work on the total chemical synthesis of the dragmacidins, primarily from the Stoltz laboratory in the case of dragmacidins D and F, has emerged over the past two decades.…”