A New Approach to the Synthesis of Etoposide (VP 16)

Kolář, Čenêǩ; Moldenhauer, Hans; Kneissl, Günther

doi:10.1080/07328309008543854

Cited by 6 publications

(4 citation statements)

References 10 publications

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“…The last step, deprotection of the monochloroacetyl group, was attempted under various conditions. During the transesteriˆcation of 16 with MeOH and ionexchange resin 16) of the strongly basic type (Dowex 1 ×8 20-50 mesh), the aglycon methyl ester emerged before the glucoside had been completely deprotected. Neither the monochloroacetyl nor glycosyl ester was cleaved with resin of the weakly base type (Amberlite IR-45 or IR-4B).…”

Section: Resultsmentioning

confidence: 99%

Synthesis of the Glycosidic Precursor of Isomeric Marmelo Lactones, Volatile Components of the Quince Fruit,Cydonia oblonga

Shimizu

Kitahara

2002

Bioscience, Biotechnology, and Biochemistry

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The glucosidic precursor of marmelo lactones was synthesized by employing a common intermediate which had been used for the synthesis of the glucosidic precursor of marmelo oxides. The synthesis was performed by modifying the former procedure. Monochloroacetyl was adopted to protect both the glucose and aglycon hydroxyl groups for selective transesterification in the presence of the glycosyl ester. Glycosylation of the aglycon carboxyl group with 1-alpha-bromopermonochloroacetylglucose and final selective alcoholysis yielded the target glucoside.

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Section: Resultsmentioning

confidence: 99%

Synthesis of the Glycosidic Precursor of Isomeric Marmelo Lactones, Volatile Components of the Quince Fruit,Cydonia oblonga

Shimizu

Kitahara

2002

Bioscience, Biotechnology, and Biochemistry

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“…Indeed treatment of the crude azido sugar mixture 2 with tert -butyldimethylsilyl chloride in the presence of imidazole afforded the azido derivatives of β- d - ribo and β- d - arabino configuration, 3 and 4 , respectively, in 75% overall yield and 1:2 ratio. Subsequent transesterification (NaOMe−MeOH) led to the corresponding 4,6-diols 5 and 6 which were immediatly protected as their chloroacetyl esters 7 and 8 . Alternatively, these azido sugars 5 and 6 were converted into their 4,6- O -ethylidene acetals 9 and 10 , with the acetal group present in etoposide itself, by treatment with 1,1-diethoxyethane/TsOH.…”

Section: Chemistrymentioning

confidence: 99%

“…Subsequent transesterification (NaOMe-MeOH) led to the corresponding 4,6diols 5 and 6 which were immediatly protected as their chloroacetyl esters 7 and 8. 22 Alternatively, these azido sugars 5 and 6 were converted into their 4,6-O-ethylidene acetals 9 and 10, with the acetal group present in etoposide itself, by treatment with 1,1-diethoxyethane/TsOH.…”

Section: Chemistrymentioning

confidence: 99%

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Synthesis and Antitumor Activity of New Glycosides of Epipodophyllotoxin, Analogues of Etoposide, and NK 611

et al. 1998

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A series of 3-amino- and 3-alkylamino-2-deoxy-beta-D-ribo- and beta-D-arabino-glycosides of 4'-demethylepipodophyllotoxin have been synthesized by means of an improved trimethylsilyliodide procedure for the podophyllotoxin-4'-demethylepipodophyllotoxin conversion, an efficient and high yielding synthesis of silyl glycoside donors of 3-azido-2,3-dideoxy-beta-D-ribo- and beta-D-arabino-hexopyranosides and stereoselective glycosylations. In vitro evaluation of cytotoxic effects against murine L1210 leukemia critically demonstrates the essential role played by a 4,6-acetal for biological activity. Among the most cytotoxic compounds, 3-amino-2,3-dideoxy- and 3-N, N-(dimethylamino)-2,3-dideoxy etoposide analogues, 17 and 27-29 are at least as potent as etoposide on the in vivo P388 (iv/ip) murine leukemia models. However, surprisingly enough, none of these compounds inhibits the human DNA topoisomerases I or II or binds to tubulin to prevent its polymerization and microtubule assembly. Therefore, their mechanism of action remains to be cleared up.

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