The Knight route to cyclopiazonic acid: enantioselective synthesis of a key intermediate

Beyer, Christian; Scherkenbeck, Jürgen; Sondermann, Frank; Figge, Axel

doi:10.1016/j.tet.2010.06.092

Cited by 15 publications

(9 citation statements)

References 17 publications

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“…Although the structure of CPA has been known since 1968, only three racemic syntheses have been published to date (Haskins and Knight, 2005;Kozikowski et al, 1984;Muratake and Natsume, 1985) and very little is known on the related structure-activity relationships. Beyer et al (2010Beyer et al ( , 2011 reported the first structure-activity data of several CPA derivatives and stereoisomers as well as the first asymmetric total synthesis of CPA by a modification of the Knight synthesis, currently the most efficient route to produce CPA.…”

Section: Cyclopiazonic Acid Chemistrymentioning

confidence: 99%

Cyclopiazonic acid: 50th anniversary of its discovery

Ostrý¹,

Toman

Grosse

et al. 2018

WMJ

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In 1968, the mycotoxin cyclopiazonic acid (CPA) was first discovered and characterised as a chemical substance. Within the following five decades, much has been learned from the results of CPA research. CPA is produced by several Penicillium species (P. griseofulvum, P. camemberti, P. commune, P. dipodomyicola) and Aspergillus species (A. flavus, A. oryzae and A. tamarii). It is widespread on naturally contaminated agricultural raw materials. CPA has been reported to occur in food commodities (e.g. oilseeds, nuts, cereals, dried figs, milk, cheese and meat products) and to possess toxicological significance. CPA is also frequently detected in peanuts and maize; the presence of CPA and aflatoxins in maize and peanuts contaminated with A. flavus suggests that synergism may occur. CPA is toxic to several animal species, such as rats, pigs, guinea pigs, poultry and dogs. After ingesting CPA-contaminated feeds, test animals display severe gastrointestinal upsets and neurological disorders. Organs affected include the liver, kidney, heart, and digestive tract, which show degenerative changes and necrosis. Biologically, CPA is a specific inhibitor of sarco(endo)plasmic reticulum Ca2+-ATPase. Data from toxicological evaluation of aflatoxins and CPA in broiler chickens demonstrate that both aflatoxins and CPA alone and the aflatoxin-CPA combination can adversely affect broiler health. The effects of aflatoxins and CPA combination were additive in most cases.

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Section: Cyclopiazonic Acid Chemistrymentioning

confidence: 99%

Cyclopiazonic acid: 50th anniversary of its discovery

Ostrý¹,

Toman

Grosse

et al. 2018

WMJ

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“…When the reaction was performed under strictly anhydrous conditions, α‐CPA imine ( 3 ) was the major product. This constitutes the first direct synthesis of α‐CPA imine: the previous method relied on the amination of α‐CPA itself . This completed our synthesis of the α‐CPA family.…”

Section: Figurementioning

confidence: 93%

“…Kozikowski and Natsume constructed the C–D rings in a stepwise manner, but with low diastereoselectivity. Knight developed an elegant cationic cascade, in which acyclic precursor 9 was converted into indole 6 with high stereocontrol,, although Scherkenbeck found that the same substrate cyclized to give a 1:1 mixture of diastereomers across the CD ring junction under slightly different conditions ,…”

Section: Figurementioning

confidence: 99%

“…Presumably, the facility of the cyclization stems from ready formation of the undistorted amino‐acyl palladium intermediate, before ring strain is introduced through the subsequent reductive elimination. Hydrolysis of N ‐Ts species 28 under basic conditions in MeOH‐THF‐H 2 O (10:10:1) provided a mixture of (−)‐α‐CPA ( 1 ) and (+)‐iso‐α‐CPA ( 2 ) (dr 2.5:1) which was separated by reverse‐phase prep‐HPLC.…”

Section: Figurementioning

confidence: 99%

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Enantioselective Synthesis of the Cyclopiazonic Acid Family Using Sulfur Ylides

et al. 2018

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Ac onvergent, nine-step (LLS), enantioselective synthesis of a-cyclopiazonic acid and related natural products is reported. The route features a) an enantioselective aziridination of an imine with ac hiral sulfur ylide;b )abioinspired (3+ +2)-cycloaddition of the aziridine onto an alkene;a nd c) installation of the acetyltetramic acid by an unprecedented tandem carbonylative lactamization/NÀOc leavage of ab romoisoxazole.

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“…15 The key step here is a simultaneous formation of the ring C-and D-framework by a cationic cyclization of the bicyclic intermediate 12 (Scheme 2), which is available in enantiomeric pure form on a multigram scale by a 1,4-addition (dr 94:6) of isopropenylcuprate to the chiral indolyl acrylic acid 11 (Scheme 2), followed by a 1,2-addition of trisylazide (dr 98:2) as detailed recently by our group. 16 Remarkably, both stereogenic centres are established in the correct configuration by one and the same Evans auxiliary with high diastereofacial control.…”

Section: Introductionmentioning

confidence: 99%