Total Syntheses of (−)-Majucin and (−)-Jiadifenoxolane A, Complex Majucin-Type <i>Illicium</i> Sesquiterpenes

Condakes, Matthew L.; Hung, Kevin; Harwood, Stephen J.; Maimone, Thomas J.

doi:10.1021/jacs.7b11493

Cited by 45 publications

(25 citation statements)

References 55 publications

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“…In 2009, we disclosed a proof-of-concept to efficiently access highly oxidized terpenes that holistically mimics this underlying logic of biosynthesis . Two-phase terpene synthesis logic, despite lacking convergency, could be applied to concise syntheses of complex systems such as ingenol, phorbol, thapsigargin, and others. , Application of this strategy to the non-skeletally rearranged taxanes, of which 1 resides at the apex of structural complexity, remained aspirational for the past decade. This can be visualized in Figure , with a hypothetical retrosynthetic pyramid for the two-phase synthesis of 1 requiring a chemist to navigate no less than nine different C–O bond-forming steps from a minimally oxidized taxane precursor such as taxadienone ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Two-Phase Synthesis of Taxol

et al. 2020

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Taxol® is widely regarded as amongst the most famed natural isolates ever discovered, and has been the subject of innumerable studies in both basic and applied science. Its documented success as an anticancer agent, coupled with early concerns over supply, stimulated a furious worldwide effort from chemists to provide a solution for its preparation through total synthesis. Those pioneering studies proved the feasibility of retrosynthetically-guided access to synthetic Taxol, albeit in minute quantities and with enormous effort. In practice, all medicinal chemistry efforts and eventual commercialization have relied upon natural-(plant material) or biosynthetically-derived (synthetic biology) supplies. Here we show how a complementary divergent synthetic approach that is holistically patterned off of biosynthetic machinery for terpene synthesis can be used to arrive at Taxol®. File list (2) download file view on ChemRxiv Manuscript.pdf (1.42 MiB) download file view on ChemRxiv Supporting Information.pdf (67.60 MiB)

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Section: Introductionmentioning

confidence: 99%

Two-Phase Synthesis of Taxol

et al. 2020

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“…In contrast to the elusive C–H oxygenation − in biosynthetic proposals, the derivatization through an olefin intermediate would be much more doable in achieving chemo- and stereoselectivity. We anticipated that the olefinic compound 6 could be generated through site-selective desaturation from dilactone 5 .…”

Section: Resultsmentioning

confidence: 97%

Site-Specific Photochemical Desaturation Enables Divergent Syntheses of Illicium Sesquiterpenes

Shen

Xiao

et al. 2021

J. Am. Chem. Soc.

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Desaturation of unactivated alkanes remains a challenging yet desirable strategy to make olefins. The Illicium sesquiterpenes usually possess highly oxygenated cage-like architectures, and some of them exhibit prominent neurotrophic effects. Here, we disclose a unique photochemical desaturation strategy for the efficient, highly stereocontrolled total syntheses of five Illicium sesquiterpenes from inexpensive (R)-pulegone, featuring a 13-step gram-scale synthesis of (−)-merrilactone A. The efficiency of the syntheses derives from an expedient construction of a tetracyclic framework via two annulations, a site-specific photoinduced singlestep desaturation in a complex hydrocarbon system, and diverse oxygenation manipulations around the resultant olefin intermediate. This work highlights how late-stage desaturation can dramatically streamline the synthesis of complex terpenes and diverse nonnatural analogues for establishing the structure−activity relationship and elucidating their molecular mechanisms of bioactivity.

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“…(À)-Majucin and (À)-jiadifenoxolane A. Maimone et al reported the rst synthetic route to complex majucin-type natural products (À)-majucin ((À)-320) and (À)-jiadifenoxolane A ((À)-321) starting from the abundant feedstock (+)-cedrol ((+)-304). 284,[476][477][478][479] The synthesis commenced with a Suárez oxidation, followed by a hydroboration/double oxidation Overall, 13 oxidations were employed while three reduction steps were necessary to achieve the correct oxidation state and for stereochemical adjustments. Favorable aspects in the light of "green" chemistry are the use of a photocatalyzed reaction, and of green solvents (acetone, H 2 O, MeOH), yet undesired solvents like CCl 4 or PhCF 3 also occur.…”

Section: Terpenesmentioning

confidence: 99%