150240-39-4Relevant articles and documents
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.
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.
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.
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%).
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.
