Synthesis of the Tetracyclic Framework of the Erythrina Alkaloids Using a [4 + 2]-Cycloaddition/Rh(I)-Catalyzed Cascade of 2-Imidofurans

Padwa, Albert; Wang, Qiu

doi:10.1021/jo061269p

Cited by 59 publications

(27 citation statements)

References 120 publications

(68 reference statements)

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“…Alternative methods for the removal of Boc protecting groups in the presence of acid labile moieties have been described. [15][16][17][18][19] Following some investigations, zinc bromide (ZnBr 2 ) in DCM in the presence of a catalytic amount of H 2 O provided amine 7 in 80% yield.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of prolyl oligopeptidase with a synthetic unnatural dipeptide

Racys¹,

Rea²,

Fülöp³

et al. 2010

Bioorganic & Medicinal Chemistry

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The synthesis of a new inhibitor of prolyl oligopeptidase, containing a piperidine ring, together with an X-ray structure of its complex with the enzyme, is described. This provides evidence that covalent inhibitors of POP do not have to be limited to structures containing 5-membered N-containing heterocyclic rings. inhibitor:Leave this area blank for abstract info. Abstract-A new inhibitor, containing a linked proline-piperidine structure, for the enzyme prolyl oligopeptidase (POP) has been synthesised and demonstrated to bind covalently with the enzyme at the active site. This provides evidence that covalent inhibitors of POP do not have to be limited to structures containing 5-membered N-containing heterocyclic rings.

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Section: Resultsmentioning

confidence: 99%

Inhibition of prolyl oligopeptidase with a synthetic unnatural dipeptide

Racys¹,

Rea²,

Fülöp³

et al. 2010

Bioorganic & Medicinal Chemistry

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“…Padwa [6,15] This reaction, which involves a cyclization, decarboxylation and an aromatization step, presumably proceeds by a mechanism similar to that suggested for the formation of 5,8,9,10-tetrahydro-6H-indoloA C H T U N G T R E N N U N G [2,1-a]isoquinolin-9-ones 14a-c. The synthesis of 5,8,9,10-tetrahydro-6H-indoloA C H T U N G T R E N N U N G [2,1-a]isoquinolin-9-ones has, to the best of our knowledge, not been reported to date.…”

Section: Resultsmentioning

confidence: 99%

“…[4][5][6] This transformation proceeds by acid-catalyzed cyclization of the amide to give an N-(2-arylethyl)-2-oxo-1,2,3,4,5,6-hexahydroindole which is transformed in situ into the Erythrina-type spirocyclic product by a Pictet-Spengler reaction. For example, spirocycle I has been directly prepared from the amide II under various conditions (use of acids or Lewis acids) (Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 2,6‐Dioxo‐1,2,3,4,5,6‐hexahydroindoles by Acid‐ Catalyzed Cyclization of Acetal‐Protected (2,4‐Dioxocyclohex‐1‐yl)acetamides and their Transformation into 5,8,9,10‐Tetrahydro‐6H‐indolo[2,1‐a]isoquinolin‐9‐ones

et al. 2009

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Acetal-protected (2,4-dioxocyclohex-1-yl)-acetic acids were prepared by allylation of dilithiated 1,3-cyclohexane-1,3-diones, protection of the carbonyl groups and oxidation of the alkene moiety. Their reaction with amines afforded the corresponding amides which were transformed, by acid-catalyzed cyclization, into various 2,6-dioxo-1,2,3,4,5,6-hexahydroindoles. The reaction of the latter with triflic acid resulted in the formation of novel 5,8,9,10-tetrahy-Keywords: alkaloids; amides; C À C bond formation; cyclization; nitrogen heterocycles IntroductionErythrina alkaloids occur in various tropical and subtropical plants [1] and show a wide range of interesting biological properties.[2] This includes, for example, curare-like, hypotensive, sedative, anticonvulsive, and CNS-depressive activity.[3] Erythrina alkaloids have been prepared, for example, using photochemical [2 + 2] cycloadditions or Diels-Alder reactions as the key steps.[4] An important strategy for the synthesis of Erythrina alkaloids relies on the acid-catalyzed domino reaction of (2-oxocyclohex-1-yl)acetic amides. [4][5][6] This transformation proceeds by acid-catalyzed cyclization of the amide to give an N-(2-arylethyl)-2-oxo-1,2,3,4,5,6-hexahydroindole which is transformed in situ into the Erythrina-type spirocyclic product by a Pictet-Spengler reaction. For example, spirocycle I has been directly prepared from the amide II under various conditions (use of acids or Lewis acids) (Scheme 1). Despite its utility, the preparative scope of this reaction is very narrow and its success strongly depends on the structure of the substrate (substitution pattern of the aryl group, length of the linker between the aryl group and the nitrogen atom, etc.). This is a severe limitation because the synthesis of specific target molecules heavily relies on functional group transformations of the spiro compounds obtained by the domino process. FULL PAPERSTo address this problem, we planned to prepare the unknown Erythrina derivative III, which contains an additional carbonyl group, from the corresponding amide IV (Scheme 1). The carbonyl group of III was expected to be a useful tool for the synthesis of Erythrina-type natural products and their non-natural analogues. It was planned to prepare the required starting material IV from (2,4-dioxocyclohex-1-yl)acetic acid which, therefore, represents an important key intermediate of the present study.Recently, we have reported [7] preliminary results related to the synthesis of (2,4-dioxocyclohex-1-yl)acetic amides, such as IV. Their cyclization, in the presence of catalytic amounts of para-toluenesulfonic acid (PTSA), resulted in the formation of 2,6-dioxo-1,2,3,4,5,6-hexahydroindoles rather than the expected Erythrina-type spiro compounds. Herein, we report a full account of the preparative scope of this methodology which provides, to the best of our knowledge, the as yet most general approach to 2,6-dioxo-1,2,3,4,5,6-hexahydroindoles.

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“…40 The asymmetric radical trichloromethylation reaction with BrCCl 3 developed by Zakarian and coworkers (eq 17) has been employed as a key element in the synthesis of a subfamily of marine natural products biosynthetically derived from trichloroleucine. Examples include neodysidenin, 28a barbamide, 41 dysidin, and dysidenin.…”

Section: N-alkoxy-5-(p-methoxyphenyl)-4-methylthiazole-2(3h)-thionesmentioning

confidence: 99%