Studies concerning the antibiotic actinonin. Part III. Synthesis of structural analogues of actinonin by the anhydride–imide method

Devlin, John P.; OLLIS, W. DAVID; Thorpe, John E.; Wood, Ronald J.; Broughton, Barbara J.; Warren, Peter J.; Wooldridge, K. R. H.; Wright, Derek E.

doi:10.1039/p19750000830

Cited by 21 publications

(10 citation statements)

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“…93 About 20 years later, actinonin was also obtained from another strain referenced MG848-hF6 and its inhibition against APN was found to be competitive with the substrate. 94 The structural study and the chemical synthesis of 13 and some analogues have aroused numerous works [95][96][97][98][99][100][101][102] completed by a structure-activity relationship investigation dealing with anti bacterial properties observed in this actinonin series. 103…”

Section: A Naturally Occurring Apn/cd13 Inhibitorsmentioning

confidence: 99%

Aminopeptidase-N/CD13 (EC 3.4.11.2) inhibitors: Chemistry, biological evaluations, and therapeutic prospects

Bauvois¹,

Dauzonne²

2005

Med. Res. Rev.

233

162

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Aminopeptidase N (APN)/CD13 (EC 3.4.11.2) is a transmembrane protease present in a wide variety of human tissues and cell types (endothelial, epithelial, fibroblast, leukocyte). APN/CD13 expression is dysregulated in inflammatory diseases and in cancers (solid and hematologic tumors). APN/CD13 serves as a receptor for coronaviruses. Natural and synthetic inhibitors of APN activity have been characterized. These inhibitors have revealed that APN is able to modulate bioactive peptide responses (pain management, vasopressin release) and to influence immune functions and major biological events (cell proliferation, secretion, invasion, angiogenesis). Therefore, inhibition of APN/CD13 may lead to the development of anti-cancer and anti-inflammatory drugs. This review provides an update on the biological and pharmacological profiles of known natural and synthetic APN inhibitors. Current status on their potential use as therapeutic agents is discussed with regard to toxicity and specificity.

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Section: A Naturally Occurring Apn/cd13 Inhibitorsmentioning

confidence: 99%

Aminopeptidase-N/CD13 (EC 3.4.11.2) inhibitors: Chemistry, biological evaluations, and therapeutic prospects

Bauvois¹,

Dauzonne²

2005

Med. Res. Rev.

233

162

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“…Herein, we describe a CC‐bond‐formation method based on the electro‐reductive coupling of activated olefins and benzyl bromide derivatives. The coupling products such as 2‐benzyl succinic acid dimethyl ester are important classes of compounds owing to their utility as intermediates in the synthesis of important targets such as natural antibiotics,5a pyrrolidines,5b metalloproteinase inhibitors,5c inhibitors towards human leukocytes,5d cephalotaxine,5e and monoesters of alkylated succinic acids 5f. Several methods have been reported5b,g,h for this class of compounds, most of which involve multi‐step processes and require the presence of metal catalysts.…”

Section: Data For the Preparative Electrolysis Of Activated Olefins Imentioning

confidence: 99%

Self‐Supported and Clean One‐Step Cathodic Coupling of Activated Olefins with Benzyl Bromide Derivatives in a Micro Flow Reactor

et al. 2006

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Currently coupled: A clean microreactor‐based electrosyntheses in the absence of supporting electrolyte is demonstrated and shown to feature very simple cell geometries. As exemplified for the coupling reaction of various olefins with benzyl bromides, the height of the microfluidic cell and the flow rate are crucial for the minimization of unwanted side products and optimization of yields (see picture).

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“…3-Alkyl-dihydro-furan-2,5-diones (3-alkyl succinic anhydrides) and (E)-3-alkylidene-dihydro-furan-2,5-diones [(E)-3-alkylidene succinic anhydrides] are both important class of compounds due to their utility as intermediates in the synthesis of important targets such as natural antibiotics, 1,2 pyrrolidines, 3 metalloproteinase inhibitors, 4 inhibitors towards human leukocytes, 5 cephalotaxine, 6 and monoesters of alkylated succinic acids. 7 Although several methods have been reported [3][4][5][6][7][8][9][10][11][12] for the preparation of the title compounds, they seem not of general applicability.…”

mentioning

confidence: 99%

Nitroalkanes and Dimethyl Maleate as Source of 3-Alkyl Succinic Anhydrides and (E)-3-Alkylidene Succinic Anhydrides

Ballini¹,

Bosica²,

Fiorini³

et al. 2002

Synthesis

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Nitroalkanes react with dimethyl maleate giving a tandem Michael addition/elimination of nitrous acid. The obtained (E)-2-alkylidene dimethyl succinates are: (i) reduced to the corresponding 2-alkyl dimethyl succinates which after hydrolysis produce 1,4-dicarboxylic acids that are prone to convert into the corresponding 3-alkyl succinic anhydrides or (ii) hydrolysed to (E)-2-alkylidenesuccinic acids that are easily cyclised to (E)-3-alkylidene succinic anhydrides.3-Alkyl-dihydro-furan-2,5-diones (3-alkyl succinic anhydrides) and (E)-3-alkylidene-dihydro-furan-2,5-diones [(E)-3-alkylidene succinic anhydrides] are both important class of compounds due to their utility as intermediates in the synthesis of important targets such as natural antibiotics, 1,2 pyrrolidines, 3 metalloproteinase inhibitors, 4 inhibitors towards human leukocytes, 5 cephalotaxine, 6 and monoesters of alkylated succinic acids. 7 Although several methods have been reported 3-7,8-12 for the preparation of the title compounds, they seem not of general applicability.Recently, an interesting methodology for the preparation of 3-alkyl succinic anhydrides has been published. 7d However, a more efficient procedure for the synthesis of both the anhydrides is still desirable.Over the last decade aliphatic nitro compounds have demonstrated to be a valuable source for the preparation of alkylated heterocyclic derivatives. 13 In continuation of our studies we wish to report here a general synthesis of both 3-alkyl succinic anhydrides 6 and (E)-3-alkylidene succinic anhydrides 8, using nitroalkanes 1 and dimethyl maleate 2 as common starting materials. Conjugate addition (Scheme) of the nitronate, derived from the nitro compound 1, to 2 in acetonitrile with DBU as base allows the formation of the product 3, essentially as single stereoisomer of E configuration. 13a,14 The adduct 3 is obtained pure enough and can be directly used without purification as the key building block for the synthesis of the anhydrides 6 or 8 by two different synthetic sequences.Scheme Synthesis of compounds 6a-k and 8a-e.Thus, chemoselective hydrogenation (10% Pd/C as catalyst) of the C=C double bond of the crude compound 3 yields the saturated diester 4 (80-98% from 1). Saturated diester 4 after hydrolysis with aqueous 2% sodium hydroxide and ethanol at reflux temperature provides the dicarboxylic acid 5 (63-90%).Although several methods are available for the conversion of 1,4-dicarboxylic acids into the corresponding anhydrides, we chose acetyl chloride 15 as a dehydrating agent for the preparation of 6 in high yields (85-98%, Table 1). On the other hand, the basic hydrolysis of the crude adduct 3 (2% sodium hydroxide solution) allows the formation of the 2-alkylidene succinic acid 7 (71-95%). The 2-alkylidene succinic acids 7 are converted to the (E)-2-alkylidene succinic anhydrides 8 in excellent yield (87-98%) following the previous procedure for the anhydrides 6. R R 1 NO 2 COOMe COOMe COOMe COOMe R R 1 COOH COOH R R 1 O R 1 R O O COOMe COOMe R R 1 COOH COOH R R 1 O R 1 R O...

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Studies concerning the antibiotic actinonin. Part III. Synthesis of structural analogues of actinonin by the anhydride–imide method

Cited by 21 publications

References 0 publications

Aminopeptidase-N/CD13 (EC 3.4.11.2) inhibitors: Chemistry, biological evaluations, and therapeutic prospects

Aminopeptidase-N/CD13 (EC 3.4.11.2) inhibitors: Chemistry, biological evaluations, and therapeutic prospects

Self‐Supported and Clean One‐Step Cathodic Coupling of Activated Olefins with Benzyl Bromide Derivatives in a Micro Flow Reactor

Nitroalkanes and Dimethyl Maleate as Source of 3-Alkyl Succinic Anhydrides and (E)-3-Alkylidene Succinic Anhydrides

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