Divergent and Efficient Syntheses of the Lycopodium Alkaloids (−)‐Lycojaponicumin C, (−)‐8‐Deoxyserratinine, (+)‐Fawcettimine, and (+)‐Fawcettidine

Abstract

Vier aus einem: Die vier Titel‐Alkaloide (Strukturen sind im blauen Kasten gezeigt) wurden ausgehend von einem gemeinsamen Intermediat mit einem tricyclischen 6/5/5‐Gerüst synthetisiert. Die Schlüsselschritte zum Aufbau des Intermediats waren eine intramolekulare Carbenaddition/Cyclisierung und eine Dieckmann‐Kondensation/Tsuji‐Trost‐Allylierung.

The Total Synthesis of Diquinane‐Containing Natural Products

“…In 2013, Tu and Wang disclosed ad ivergent total synthesis of fawcettimine-type alkaloids, among which the first and asymmetrict otal synthesis of lycojaponicumin Cw as achieved. [22] The synthesis commenced with the Mukaiyama-type Michael addition between the known chiral cyclohexenone 44 and the vinyl diazoacetate 43 to form 45,which waseffectively achieved with triflimide as an optimal acidc atalystu nprecedentedly. [23] Subsequently,astereoselective Cu-catalyzed carbene cyclization constructed the cyclopentanone system to provide compound 46 whichw as directly subjected to Krapcho decarboxylation in one pot, giving the diketonee ster product 47.N otably,t hese three steps could be operated in one pot to provide 47 in an acceptable yield (51 %).…”

Divergent Strategy in Natural Product Total Synthesis

“…In 2013, the Lei group reported the collective total synthesis of Lycopodium alkaloids (−)-8-deoxyserratinine (888), (+)-fawcettimine ( 20), (+)-fawcettidine (889), (+)-alopecuridine (891), and (−)-lycojapodine A (892) from a common precursor 883, which has been used for the total synthesis of 888, 20, and 889, 126 inspired by the proposed biosynthesis of the fawcettimine-and serratinine-type alkaloids (Scheme 79). 127 The known enone 317 was 129 It is noteworthy that 898 is characterized with a 6/5/5 tricyclic system, which is different from the 6/5/9 tricycle of the Heathcock-inspired strategies. This key tricycle 898 was assembled from the carbene addition/cyclization, decarboxylation, and functionalization of 897, which could be prepared through Mukaiyama−Michael addition from known enone 893 and vinyl diazoacetate 894.…”

Collective Total Syntheses of Five Lycopodium Alkaloids

“…Owing to their potential biological application and complex three‐dimensional structures, these natural products have attracted widespread interest from the synthetic community. Besides early important achievements on the synthesis of some single natural products, [4] a lot of remarkable strategies resulting in collective total syntheses have been disclosed in recent years [5–9] . To conquer the divergent total syntheses of fawcettimine‐type alkaloids, Tu and co‐workers developed a copper‐catalyzed carbene cyclization strategy in 2013, [5] and Lei and co‐workers realized the remarkable “hidden functional‐group pairing pattern” in 2014 [6] .…”

“…Besides early important achievements on the synthesis of some single natural products, [4] a lot of remarkable strategies resulting in collective total syntheses have been disclosed in recent years [5–9] . To conquer the divergent total syntheses of fawcettimine‐type alkaloids, Tu and co‐workers developed a copper‐catalyzed carbene cyclization strategy in 2013, [5] and Lei and co‐workers realized the remarkable “hidden functional‐group pairing pattern” in 2014 [6] . As for lycopodine‐type alkaloids, Fan and co‐workers invented a bridgehead C−H functionalization of the bicycle[3.3.1]nonane ring system to furnish a cluster of alkaloids of this type in 2017 [7] .…”