Total Synthesis of the Potent cAMP Signaling Agonist (−)-Alotaketal A

Huang, Jinhua; Yang, Jessica R.; Zhang, Jin; Yang, Jiong

doi:10.1021/ja303529z

Cited by 42 publications

(31 citation statements)

References 39 publications

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“…Thus, these results show that 49 and 2 are active and involved in PKA activation. Together with the data showing 49 and 2 induced responses from a FRET-based cAMP indicator, 12 these results suggest that these compounds activate PKA by inducing cAMP production.…”

Section: Resultssupporting

confidence: 65%

“…Herein we report in detail our study, which culminated in the first enantioselective total synthesis of (-)-alotaketal A and illuminated the preliminary structure-activity relationship (SAR) of this potent cAMP signaling agonist. 12,13 Our study also revealed alotaketal A’s unique activity in selectively targeting PKA signaling in the nucleus of living cells.…”

Section: Introductionmentioning

confidence: 57%

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Total synthesis and structure–activity relationship study of the potent cAMP signaling agonist (−)-alotaketal A

et al. 2013

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A detailed account of the first total synthesis of alotaketal A, a tricyclic spiroketal sesterterpenoid that potently activates the cAMP signaling pathway, is provided. The synthesis employs both intra- and intermolecular reductive allylation of esters for assembling one of the fragments and their coupling. A Hg(OAc)2-mediated allylic mercuration is used to introduce the C22-hydroxyl group. The subtle influence of substituents over the course of the spiroketalization process is revealed. The synthesis confirms the relative and absolute stereochemistry of (-)-alotaketal A and allows verification of alotaketal A’s effect over cAMP signaling using reporter-based FRET imaging assays with HEK 293T cells. Our studies also revealed alotaketal A’s unique activity in selectively targeting nuclear PKA signaling in living cells.

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Section: Resultssupporting

confidence: 65%

Section: Introductionmentioning

confidence: 57%

Total synthesis and structure–activity relationship study of the potent cAMP signaling agonist (−)-alotaketal A

et al. 2013

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“…716 by two independent groups have conrmed the absolute conguration. 717,718 Four sesterterpenoids, phorone A 855, isophorbasone A 856, ansellone B 857 and phorbasone A acetate 858, were isolated from a S. Korean Phorbas sp. Compounds 857 and 858, described in the paper's supporting information, were low mM inhibitors of NO production in LPS-stimulated RAW 264.7 cells, while 855 and 856 are the rst examples of two new carbon skeletons.…”

Section: A Malaysianmentioning

confidence: 99%

Marine natural products

et al. 2014

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This review covers the literature published in 2012 for marine natural products, with 1035 citations (673 for the period January to December 2012) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1241 for 2012), together with the relevant biological activities, source organisms and country of origin. Biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included.

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“…The potent and wide array of biological activities of alotaketals and phorbaketals have attracted considerable synthetic interest. The groups of Yang, and Dalby accomplished the elegant total synthesis of 1 by similar strategies, which involved late‐stage construction of the C ring through a Barbier‐type reaction and spiroketalization. Recently, the groups of Brimble and Bray disclosed two efficient strategies for the tricyclic spiroketal core, which unfortunately could not be elaborated to the natural products.…”

Section: Figurementioning

confidence: 99%

Unified Asymmetric Total Syntheses of (−)‐Alotaketals A–D and (−)‐Phorbaketal A

et al. 2017

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The novel tricyclic spiroketal alotane-type sesterterpenoids showed strikingly different biological activities and potency with subtle structural alterations. Asymmetric total syntheses of the tricyclic sesterterpenoids (-)-alotaketals A-D and (-)-phorbaketal A were accomplished [29-31 steps from (-)-malic acid] in a collective way for the first time. The key features of the strategy included 1) a new cascade cyclization of vinyl epoxy δ-keto-alcohols to forge the common tricyclic spiroketal intermediate, 2) a late-stage allylic C-H oxidation, and 3) olefin cross-metathesis to install the different side chains.

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Total Synthesis of the Potent cAMP Signaling Agonist (−)-Alotaketal A

Cited by 42 publications

References 39 publications

Total synthesis and structure–activity relationship study of the potent cAMP signaling agonist (−)-alotaketal A

Total synthesis and structure–activity relationship study of the potent cAMP signaling agonist (−)-alotaketal A

Marine natural products

Unified Asymmetric Total Syntheses of (−)‐Alotaketals A–D and (−)‐Phorbaketal A

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