Six-Step Synthesis of Alcyopterosin A, a Bioactive Illudalane Sesquiterpene with a gem-Dimethylcyclopentane Ring

Abstract

Strategic pairing of ring openings and cycloisomerization provides rapid and efficient "open and shut" entry into sparsely functionalized illudalanes, as exemplified here in the context of a six-step synthesis of alcyopterosin A. Key steps include a tandem ring-opening fragmentation/olefination process for preparing a neopentyl-tethered 1,6-enyne, ring-opening olefination telescoped with alkyne homologation, and Rh-catalyzed oxidative cycloisomerization.

Pivotal Reactions in the Creation of the Polycyclic Skeleton of Cryptotrione

“…The first total syntheses of the architecturally complex atisane-type diterpenes and biogenetically related atisine-type diterpenoid alkaloids (±)-spiramilactone B (16), (±)-spiraminol (17), (±)-dihydroajaconine (18), and (±)-spiramines C (19) and D (20) were reported by Xu. 16 The key reactions involved a highly efficient and diastereoselective 1,7-enyne cycloisomerization to construct the functionalized tetracyclic atisane skeleton.…”

“…In 2016, Dudley disclosed a six-step synthesis of alcyopterosin A (22), a bioactive illudalane sesquiterpene with a gem-dimethylcyclopentane ring. 17 The key Rh-catalyzed cycloisomerization is outlined in Scheme 6. A solution of precursor 21 and 2,5-norbornadiene-rhodium(I) chloride dimer in trifluoroethanol (TFE) was heated at 50 °C for 8 hours under nitrogen.…”

Tipping the balance: theoretical interrogation of divergent extended heterolytic fragmentations

“…Carbon-carbon (C-C), carbonheteroatom (C-X), and heteroatom-heteroatom (X-Y) heterolytic fragmentation reactions offer methods for synthesizing structural motifs (some found in complex natural products) that might be difficult to synthesize using methods focused on bond formation. [1][2][3][4][5][6][7] Despite their continued use in organic synthesis [8][9][10][11][12][13][14][15][16][17] and their relevance to reactions occurring in mass spectrometers, 18 the application of heterolytic fragmentations in which multiple s-bonds are cleaved in synthetic campaigns is limited by putative strict conformational requirements (e.g., an anti-periplanar conformation for the bonds that cleave during fragmentation; Scheme 1). 4,19 Few theoretical and mechanistic studies [20][21][22][23][24] have provided insight into the physical underpinnings for this class of reaction since the seminal work of Grob.…”

Microwave Heating Outperforms Conventional Heating for a Thermal Reaction that Produces a Thermally Labile Product: Observations Consistent with Selective Microwave Heating

“…Selective MW heating of polar solutea ggregates is postulated to explain these observations.We recently reported as ynthesis of illudinine [1] in conjunction with broader efforts to produce targets of interestb earing neopentylene ring fusions. [2] Previously reported syntheses of illudinine required 14 [3] to 16 [4] steps, many of which were dedicated to craftingt he neopentylene ring fusion. Our reported synthesis of illudinine featured tandem fragmentation and olefination methodology from our lab, [5] and it was relativelye fficient, providings ynthetic illudinine in 8steps and 14 %o verall yield from commerciallyavailable dimedone (Scheme 1).Our synthesis of illudinine featured ak ey oxidative cycloisomerization (Scheme 2).…”