Preparation of novel heterocyclic amino acids from N-(arylmethylene)dehydroalanine methyl esters

Wulff, Günter; Klinken, H. T.

doi:10.1016/s0040-4020(01)89847-1

Cited by 24 publications

(16 citation statements)

References 15 publications

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“…Homodimerization of 36 was found to take place in Diels-Alder type fashion (37) even at low temperatures. In accordance with earlier work [43][44][45] the initial dehydropiperidine product 38 was highly prone to imine-enamine tautomerization, followed by an intramolecular aza-Mannich reaction. This unintended sequence could be suppressed using a scavenging amine (BnNH 2 ), which removed the side-chain imine and liberated the labile amino-dehydropiperidine product 39 as a 1 : 1 mixture of diastereomers (separable later in the synthesis).…”

Section: Thiostreptonsupporting

confidence: 89%

Biomimetic Synthesis of Azole‐ and Aryl‐Peptide Alkaloids

Arndt

Lichtenecker

Loos

et al. 2011

Biomimetic Organic Synthesis

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Section: Thiostreptonsupporting

confidence: 89%

Biomimetic Synthesis of Azole‐ and Aryl‐Peptide Alkaloids

Arndt

Lichtenecker

Loos

et al. 2011

Biomimetic Organic Synthesis

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“…A previously reported observation from the Wulff group17 provided an encouraging precedent for our proposed biomimetic dehydropiperidine core construction in the laboratory. Thus, azadiene 42 (Scheme 8), isolated as a crystalline solid at −90 °C, was conceived as a building block for α-amino acid synthesis 17.…”

Section: Thiostreptonmentioning

confidence: 63%

“…Upon warming, azadiene 42 spontaneously dimerized to give aza-Diels–Alder6 adduct 44 , presumably through exo transition state 43 . Under appropriate conditions, the aryl imine of 44 was preferentially hydrolyzed to afford primary amine 45 17. Although this precedent differed in key details from what we proposed to attempt (notably in that our proposed aza-Diels–Alder dimerization required an endo transition state), it nonetheless provided inspiration for our thiostrepton campaign, which we successfully completed in 2004 18…”

Section: Thiostreptonmentioning

confidence: 94%

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The art of total synthesis through cascade reactions

2009

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The growing importance of cascade reactions reflects and imparts advances in the state of the art of organic synthesis and underscores the desire of synthetic chemists to achieve higher levels of elegance and efficiency. Besides their aesthetic appeal, cascade processes offer economical and environmentally friendly means for generating molecular complexity. Because of their many advantages, these reactions have found numerous applications in the synthesis of complex molecules, both natural and designed. In this Tutorial Review, we highlight the design and execution of cascade reactions within the context of total synthesis as demonstrated with selected examples from these laboratories.

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“…2,4,5,7-Tetrasubstituted 3,6-diazabicyclo-[3.2.1]oct-2-enes are formed via dimerization of aza dienes, followed by stereoselective intramolecular azaMannich cyclization. However, this reaction is accompanied by side processes, and the substituents in positions 2/5 and 4/7 are equivalent in pairs [14,15]. Taking the above stated into account, the transformation of cis-pyrrolidine-2,4-dicarboxylic acid monoamide, shown in Scheme 1, was examined in more detail.…”

mentioning

confidence: 99%

Synthesis of bridged heterocycles from cis-pyrrolidine-2,4-dicarboxylic acids: I. 3,6-Diazabicyclo[3.2.1]octanes

Kudryavtsev

2010

Russ J Org Chem

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cis-5-Arylpyrrolidine-2,4-dicarboxylic acid monoamides undergo thermal intramolecular condensation with formation of bicyclic imides having a 3,6-diazabicyclo[3.2.1]octane skeleton. The use of copper(I) cyanide as catalyst ensures high yields of 3,6-diazabicyclo[3.2.1]octane-2,4-diones substituted at the 3-, 5-, 6-, and 7-positions. (1R*,5R*,7S*)-7-(4-Chlorophenyl)-5,6-dimethyl-3,6-diazabicyclo[3.2.1]octane-2,4-dione was found to inhibit thrombin in a buffer solution at a millimolar concentration.Numerous natural and physiologically active compounds contain a substituted azabicyclo[3.2.1]octane fragment in their molecules. Examples are alkaloids of the tropane [1] and calystegine series [2], which possess a 8-azabicyclo[3.2.1]octane (tropane) structural fragment. (-)-Cocaine (I) is the most known alkaloid of the tropane family. Due to broad spectrum of their neurological and psychiatric effects enantiomerically pure tropane derivatives are targets of synthetic schemes developed by different research teams [3]. 6-Azabicyclo[3.2.1]octane derivatives, e.g., actinobolamine (II) [4], are encountered in nature more rarely, but they also exhibit a broad spectrum of pharmacological activity [5]. Aplaminal (III) which is a functionalized 3,6,8-triazabicyclo[3.2.1]octane derivative was isolated from the sea hare Aplysia kurodai and was found to exhibit cytotoxicity against Hela S 3 tumor cells [6].One of the main approaches to pharmacotherapy of cocaine addiction is based on the use of cocaine antagonists which inhibit cocaine recognition and its binding to dopamine transporter (DAT) but retain other important functions of that membrane protein [7]. The simplest route to the development of cocaine antagonists is synthesis of its structural analogs that are still capable of binding to DAT but exhibit reduced ability to inhibit dopamine transport and low toxicity. Some progress in this line was achieved with the use of structural isomers of tropane and its aza analogs, 3-azabicyclo[3.2.1]octanes IV (X = Y = C; isotropanes) [8] and 3,8-diazabicyclo[3.2.1]octanes IV (X = N, Y = C) [9] as central fragment in cocaine antagonists. The present article reports on a new method of synthesis of 3,6-diazabicyclo[3.2.1]octanes IV (X = C, Y = N) with different substituents in four positions of the bicyclic skeleton. These compounds are isostructural to tropane but are more basic. The products were also tested for inhibitory activity against thrombin (factor IIA).The formation of a substituted 3,6-diazabicyclo-[3.2.1]octane skeleton was revealed when 5-(4-bromophenyl)pyrrolidine-2,4-dicarboxylic acid derivative V was heated in DMF in the presence of copper(I) cyanide (Scheme 1). This reaction was initially carried out with a view to replace the bromine atom in the aromatic ring of V by cyano group (a classical Rosenmund-von Braun procedure for the synthesis of benzonitriles via aromatic nucleophilic substitution of bromine by cyano group [10]) to obtain 5-(4-cyanophenyl)pyrrolidine-2,4-dicarboxylic acid derivative.

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Preparation of novel heterocyclic amino acids from N-(arylmethylene)dehydroalanine methyl esters

Cited by 24 publications

References 15 publications

Biomimetic Synthesis of Azole‐ and Aryl‐Peptide Alkaloids

Biomimetic Synthesis of Azole‐ and Aryl‐Peptide Alkaloids

The art of total synthesis through cascade reactions

Synthesis of bridged heterocycles from cis-pyrrolidine-2,4-dicarboxylic acids: I. 3,6-Diazabicyclo[3.2.1]octanes

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