150240-39-4Relevant academic research and scientific papers
A simple and efficient synthesis of the ras farnesyl-protein transferase inhibitor chaetomellic acid A
Argade, Narshinha P.,Naik, Rajan H.
, p. 881 - 883 (1996)
A simple and efficient synthesis of the ras farnesyl-protein transferase inhibitor chaetomellic acid A anhydride (1) is reported. The imidazopyridinium bromide S obtained from the reaction of 2-bromopalmitoyl chloride and 2-aminopyridine was reacted with maleic anhydride in the presence of NaOAc/AcOH to form 1 in 62% overall yield in three steps.
Expedient assembly of bioactive maleic anhydrides using click diels-alder chemistry
Boukouvalas, John,Thibault, Charles,Loach, Richard P.
, p. 2139 - 2142 (2014)
A versatile pathway to substituted maleic anhydrides is illustrated by the synthesis of the nanomolar FTase inhibitor chaetomellic anhydride A, a germination promoter, and a novel bis-anhydride cross-linking reagent for cell or tissue fixation. Starting from commercial or easily prepared alkynes, these targets were assembled in two steps by click-unclick oxazole-alkyne cycloaddition-cycloreversion and furan oxyfunctionalization. Georg Thieme Verlag Stuttgart, New York.
Synthesis of protein farnesyltransferase and protein geranylgeranyltransferase inhibitors: Rapid access to chaetomellic acid A and its analogues
Ratemi, Elaref S.,Dolence, Julia M.,Poulter, C. Dale,Vederas, John C.
, p. 6296 - 6301 (1996)
A facile two-step stereospecific synthesis of the protein farnesyltransferase inhibitor chaetomellic acid A (1) and its analogues was developed. Addition of organocuprates derived from Grignard reagents (e.g. tetradecylmagnesium chloride and CuBr·Me2S) to dimethyl acetylenedicarboxylate (DMAD) in tetrahydrofuran containing hexamethylphosphoramide was followed by capture of the resulting copper enolates with a variety of electrophiles (e.g. methyl iodide) to give dimethyl cisbutenedioate derivatives 4-11. Hydrolysis with lithium hydroxide generated the corresponding lithium carboxylates, which readily closed to 2,3-disubstituted maleic anhydrides 17-20 upon acid treatment. Compound 16, an analogue wherein the tetradecyl group of 1 is replaced by a farnesyl moiety, is 7-fold more potent than 1 as an inhibitor of protein farnesyltransferase from yeast and displays a 100:1 selectivity for this enzyme relative to yeast protein geranylgeranyltransferase. In contrast, analogue 15, which contains a geranylgeranyl side chain, shows ca. 10:1 selectivity for the latter enzyme.
Novel route to chaetomellic acid A and analogues: Serendipitous discovery of a more competent FTase inhibitor
Bellesia, Franco,Choi, Seoung-Ryoung,Felluga, Fulvia,Fiscaletti, Giuliano,Ghelfi, Franco,Menziani, Maria Cristina,Parsons, Andrew F.,Poulter, C. Dale,Roncaglia, Fabrizio,Sabbatini, Massimo,Spinelli, Domenico
, p. 348 - 358 (2013)
A new practical route to chaetomellic acid A (ACA), based on the copper catalysed radical cyclization (RC) of (Z)-3-(2,2-dichloropropanoyl)-2- pentadecylidene-1,3-thiazinane, is described. Remarkably, the process entailed: (i) a one-pot preparation of the intermediate N-α-perchloroacyl-2-(Z)- alkyliden-1,3-thiazinanes starting from N-(3-hydroxypropyl)palmitamide, (ii) a two step smooth transformation of the RC products into ACA and (iii) only one intermediate chromatographic purification step. The method offers a versatile approach to the preparation of ACA analogues, through the synthesis of an intermediate maleic anhydride with a vinylic group at the end of the aliphatic tail, a function that can be transformed through a thiol-ene coupling. Serendipitously, the disodium salt of 2-(9-(butylthio)nonyl)-3-methylmaleic acid, that we prepared as a representative sulfurated ACA analogue, was a more competent FTase inhibitor than ACA. This behaviour was analysed by a molecular docking study.
A cobaloxime-mediated synthesis of the ras farnesyl-protein transferase inhibitor chaetomellic acid A
Branchaud, Bruce P.,Slade, Rachel M.
, p. 4071 - 4072 (1994)
A short and efficient synthesis of chaetomellic acid A anhydride (2) is reported utilizing a doubly chemoselective cross coupling of myristyl cobaloxime with citraconic anhydride and diphenyl disulfide as the key step. Sulfide oxidation followed by syn elimination provides 2 in 64% overall yield starting from myristyl bromide. Basic hydrolysis of 2 is known to provide chaetomellic acid A dianion (3), the biologically active form.
Nickel-catalyzed regio- and stereoselective double carboxylation of trimethylsilylallene under an atmosphere of carbon dioxide and its application to the synthesis of chaetomellic acid A anhydride
Takimoto, Masanori,Kawamura, Mitsunobu,Mori, Miwako,Sato, Yoshihiro
, p. 2019 - 2022 (2005)
In the presence of a nickel catalyst and excess amounts of DBU and Me 2Zn, various 1-trimethylsilylallenes smoothly reacted with two equivalents of carbon dioxide at an ambient temperature and pressure in regio- and stereoselective manners to p
Cross coupling of alkyl cobaloximes with maleic anhydrides. Basic studies and applications to the synthesis of chaetomellic acid A anhydride and C-glycosyl maleic anhydrides
Slade, Rachel M.,Branchaud, Bruce P.
, p. 3544 - 3549 (1998)
Photochemical cross coupling of alkyl cobaloximes with maleic anhydrides and PhSSPh led to addition of an alkyl moiety and an SPh moiety across the alkene. Oxidation of the sulfide to a sulfoxide followed by elimination of phenyl sulfenic acid provided substituted maleic anhydrides. Alkyl cobaloximes could also be coupled with maleic anhydrides in the absence of PhSSPh to provide substituted maleic anhydrides directly. These methods are applied to a short and efficient synthesis of the anhydride of the Ras farnesyl protein transferase inhibitor chaetomellic acid A and in preparations of C-glycosyl maleic anhydrides, in which the carbohydrate anomeric carbon is directly attached to a maleic anhydride alkene carbon, in modest yields (19-46%).
Gold-Catalyzed Cycloisomerization of Propargyl Pyruvates Enabling Unified Access to Tricladolides C and D, Chaetomellic Anhydride A, and Tyromycin A
Amin, Pathan Mosim,Su, Zhenjie,Wang, Shaozhong
, p. 15318 - 15325 (2021/11/01)
Gold-catalyzed cycloisomerization of propargyl pyruvates has been developed as a key reaction to prepare maleic anhydride-type natural products. By combining with chemoselective epoxidation of the formed γ-alkylidenebutenolides and oxidative cleavage of epoxides, the first synthesis of tricladolide D and racemic tricladolide C has been achieved in 52 and 16% overall yields with five to seven steps starting from commercially available compounds. Further catalytic hydrogenation of alkenylated maleic anhydrides derived from γ-alkylidenebutenolides produced chaetomellic anhydride A (19% yield for six steps) and tyromycin A (15% yield for six steps), which provides flexible synthetic approaches to these naturally occurring dialkylated maleic anhydrides distinct from the documented ones.
Regioselective monoalkylation of dimethyl alkylidenesuccinates: Simple approach to dialkyl-substituted maleic anhydrides including chaetomellic acid A
Kshirsagar, Umesh A.,Argade, Narshinha P.
, p. 1804 - 1808 (2011/07/29)
Natural and nonnatural dialkylmaleic anhydrides were readily prepared from dimethyl alkylidenesuccinates by sodium hexamethyldisilazide-induced selective monoalkylation followed by base-catalyzed hydrolysis. Georg Thieme Verlag Stuttgart - New York.
Expedient synthesis, on large scale, of aliphatic chaetomellic anhydrides from N-allyl-2,2-dichlorocarboxyamides
Ghelfi, Franco,Pattarozzi, Mariella,Roncaglia, Fabrizio,Giangiordano, Valerio,Parsons, Andrew F.
experimental part, p. 1040 - 1051 (2010/06/12)
Chaetomellic anhydride A and an analog (with two additional carbons) were obtained, on a preparative scale, starting from amides derived from the acylation of 2-(2-propenylamino)pyridine with 2,2-dichloropalmitic or 2,2-dichlorostearic acid. An alternative approach, in which the methyl substituent of the target anhydride is introduced by the carboxylic acid reactant and the long aliphatic chain is added through the allylamino moiety, proved unviable.
