Palladium-catalyzed oxidative cross-coupling of azole-4-carboxylates with indoles: an approach to the synthesis of pimprinine

Abstract

An efficient and straightforward method for the production of 5-(3-indolyl)azoles incorporating the privileged structures indoles and azoles via palladium-catalyzed double C-H bond cleavage under mild conditions was disclosed. As expected, this protocol provided an easy method for the synthesis of indole alkaloids pimprinine and WS-30581 A in moderate yields.

Discovery of Pimprinine Alkaloids as Novel Agents against a Plant Virus

“…Up to now, the synthesis of pimprinine has been accomplished by Joshi, Molina, Wu, and Zhou . Considering a series of pimprinine derivatives would be needed, Wu’s method was selected and optimized (Figure ).…”

“…Considering a series of pimprinine derivatives would be needed, Wu's method was selected and optimized (Figure 3). 25 2-Oxoacetaldehyde 3 and corresponding amino acids underwent a decarboxylation coupling reaction to give 5a−5l in 39− 83% yields. The indole nitrogen substituted products 6aa and 6ab were prepared (Figure 4) to evaluate the influence of NH on the activity.…”

Iodine and DMSO as Surrogate of Hazardous Metal and Non‐Metal Reagents in Organic Synthesis

“…The oxazole, especially when is substituted exhibits various appealing bioactive properties [442–445] . There are reports for the concerned synthesis using intermolecular cyclization [446–448] .…”

Muscarine, imidazole, oxazole and thiazole alkaloids

“…218 The nickel-catalyzed decarbonylative C-H coupling methodology between azoles and aryl/ alkenyl esters or enol derivatives has been developed and the strategy thus successfully applied to the convergent total synthesis of muscoride A 336, 219 a bis(oxazolyl) peptide alkaloid from the freshwater cyanobacterium Nostoc muscorum, and siphonazole B 337, 220 a natural product isolated from Herpetosiphon sp. Pd-catalyzed oxidative cross-dehydrogenative coupling between functionalized azole-4-carboxylates and indoles has enabled an efficient and straightforward construction of heterocyclic scaffolds of pimprinine 338, 221 originally isolated from Streptomyces pimprina in 1963. During synthetic studies on the total synthesis of telomestatin 339, a potent telomerase inhibitor originally isolated from Streptomyces anulatus 3533 SV4, a 2,4 0 -linked trioxazole unit has been efficiently prepared using Negishi coupling reactions.…”