Glucokinase-Activating Sesquinlignans from the Rhizomes of <i>Acorus tatarinowii</i> Schott

Ni, Gang; Shen, Zhufang; Lü, Yang; Wang, Yinghong; Tang, Yan; Chen, Ruo-Yun; Hao, Zhi‐You; Yu, De‐Quan

doi:10.1021/jo1022712

Cited by 46 publications

(36 citation statements)

References 15 publications

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“…Methylation of the phenolic hydroxyl (NaH, CH 3 I, THF) followed by chemoselective hydrogenation of the terminal alkene in the presence of Lindlar’s catalyst delivered 26 mg of tatanan A (83% yield over two steps). Synthetic tatanan A showed identical spectroscopic data ( 1 H and 13 C NMR) to those published for the natural product; the optical rotation for the synthetic material was of the same sign but of a notably higher value (

{false[α false]}_{D}^{20} + 55

( c 0.1, CH 3 OH); literature 6

{false[α false]}_{D}^{20} + 10

( c 0.1, CH 3 OH)).…”

Section: Resultssupporting

confidence: 56%

“…The first glucokinase activator was described in 2003 4 , and since that time pharmaceutical chemists have identified a variety of unique chemical scaffolds capable of stimulating glucokinase activity in vivo 5 . Although all glucokinase activators investigated to date are synthetic, the recent discovery of the tatanans, a novel class of naturally occurring lignan derivatives that reportedly possess potent glucokinase-activating capabilities, suggests that natural products might represent a rich resource for structurally and mechanistically new antidiabetic agents 6,7 . As a first step in exploring tatanans and the derivatives thereof as potential diabetes therapeutics, we undertook the total chemical synthesis and detailed mechanistic characterization of the glucokinase-activating properties of tatanans A, B and C.…”

mentioning

confidence: 99%

“…Tatanans are structurally unique sesquilignans recently isolated from the ethyl acetate extracts of rhizomes of Acorus tatarinowii Schott plants 6 . Tatanan A incorporates three consecutive tertiary stereocentres and three aryl substituents appended to an acyclic framework.…”

mentioning

confidence: 99%

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Enantioselective synthesis of tatanans A–C and reinvestigation of their glucokinase-activating properties

et al. 2013

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The tatanans are members of a novel class of complex sesquilignan natural products recently isolated from the rhizomes of Acorus tatarinowii Schott plants. Tatanans A, B and C have previously been reported to have potent glucokinase-activating properties that exceed the in vitro activity of known synthetic antidiabetic agents. Here, using a series of sequential [3,3]-sigmatropic rearrangements, we report the total synthesis of tatanan A in 13 steps and 13% overall yield. We also complete a concise enantioselective total synthesis of more complex, atropisomeric tatanans B and C via a distinct convergent strategy based on a palladium-catalysed diastereotopic aromatic group differentiation (12 steps, 4% and 8% overall yield, respectively). A plausible biosynthetic relationship between acyclic tatanan A and spirocyclic tatanans B and C is proposed and probed experimentally. With sufficient quantities of the natural products in hand, we undertake a detailed functional characterization of the biological activities of tatanans A–C. Contrary to previous reports, our assays utilizing pure recombinant human enzyme demonstrate that tatanans do not function as allosteric activators of glucokinase.

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{false[α false]}_{D}^{20} + 55

( c 0.1, CH 3 OH); literature 6

{false[α false]}_{D}^{20} + 10

( c 0.1, CH 3 OH)).…”

Section: Resultssupporting

confidence: 56%

mentioning

confidence: 99%

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Enantioselective synthesis of tatanans A–C and reinvestigation of their glucokinase-activating properties

et al. 2013

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“…Tatarinans T and S delayed the Aβ-induced paralysis in CL4176 transgenic C. elegans model at concentration of 100µM, in which tatarinan S exhibited the higher protective effect, with its PT 50 was 62.3% at 100µM and 30.8% at 10μM, respectively (Luo et al 2016). Tatanans A~C displayed potent and selective in vitro GK activity higher than positive control GKA22 (Ni et al 2011). …”

Section: Activities Of the Novel Compounds From Atsmentioning

confidence: 97%

“…Tatanans A, B and C are novel sesquinlignans (Ni et al 2011), while tatarinan T is dimeric lignan with the rare C8-C7' linkage pattern (Luo et al 2016). …”

Section: Lignansmentioning

confidence: 99%

Constituents and Activities of Acorus tatarinowii

Yang

Yan

Chen

et al. 2017

MRAJ

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Short Enantioselective Total Synthesis of Tatanan A and 3‐epi‐Tatanan A Using Assembly‐Line Synthesis

2016

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Short and highly stereoselective total syntheses of the sesquilignan natural product tatanan Aa nd its C3 epimer are described. An assembly-line synthesis approach,using iterative lithiation-borylation reactions,w as applied to install the three contiguous stereocenters with high enantio-and diastereoselectivity.One of the stereocenters was installed using aconfigurationally labile lithiated primary benzyl benzoate,r esulting in high levels of substrate-controlled (undesired) diastereoselectivity.However,reversal of selectivity was achieved by using an ovel diastereoselective Matteson homologation. Stereospecific alkynylation of ah indered secondary benzylic boronic ester enabled completion of the synthesis in at otal of eight steps.Iterative strategies are highly attractive for the synthesis of complex molecules, [1] particularly when minimal or no functional-group manipulations between chain-extension steps are required. [2,3] Iterative aldol reactions provide one such strategy, [3] but if the target molecule is devoid of appropriate functional-group handles,a lternative methodologies are required. We recently reported an iterative strategy for the homologation of boronic esters that notably does not require any functional-group manipulations between chain-extension steps. [4,5] Theprocess involves the repeated addition of chiral lithiated carbamates or triisopropylbenzoate (TIB) esters and leads to carbon chains bearing multiple contiguous methylsubstituted stereogenic centers ( Figure 1A). This approach enabled the generation of extended chains of vicinal stereocenters (up to 10) with complete control over the relative and absolute stereochemistry and applications to complex natural products have also been reported. [6] Thepower of iterative homologation of boronic esters lies in its versatility since other alkyl groups can be easily incorporated simply by varying the groups on the lithiated benzoate reagent. In extending the reach of this method, we sought to introduce aryl substituents as this would enable access to an even broader array of targets,f or example tatanan A( 1)a nd iryantherin K( 2)( Figure 1B). [7,8] We targeted the sesquilignan tatanan A( 1)a st his structurally unique molecule had been reported to display potent glucokinase-activating properties,t hereby having implications for the development of antihyperglycemic drugs, although its bioactivity has since been questioned by Zakarian, who also reported its first synthesis. [9] Thes ynthesis of such am olecule would require homologation with am ixture of alkyl-and aryl-substituted lithiated benzoates.W hilst alkyl-substituted lithiated benzoates were known to be effective in assembly-line synthesis,l ittle was known about the aryl-substituted lithiated benzoates. [10,11] Such species present additional challenges in that, unlike the alkylsubstituted lithiated benzoates,t hey are configurationally

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Glucokinase-Activating Sesquinlignans from the Rhizomes of Acorus tatarinowii Schott

Cited by 46 publications

References 15 publications

Enantioselective synthesis of tatanans A–C and reinvestigation of their glucokinase-activating properties

Enantioselective synthesis of tatanans A–C and reinvestigation of their glucokinase-activating properties

Constituents and Activities of Acorus tatarinowii

Short Enantioselective Total Synthesis of Tatanan A and 3‐epi‐Tatanan A Using Assembly‐Line Synthesis

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