【药物名称】NK-611
化学结构式(Chemical Structure):
参考文献No.5070
标题:4'-Demethyl-4-epipodophyllotoxin derivs., a process for their preparation and their use as medicaments
作者:Umezawa, H.; Takeuchi, T.; Kondo, S.; Tanaka, W.; Takita, T.; Nishimura, Y.; Yoshikawa, H. (Microbial Chemistry Research Foundation)
来源:EP 0196618; ES 8706713; JP 1986227590; US 4716221
合成路线图解说明:

The partial demethylation of (?-podophyllotoxin (I) with HBr in ether - dichloromethane, followed by alkaline hydrolysis with BaCO3 in aqueous acetone, gives (?-4'-O-demethyl-1-epipodophyllotoxin (II), which is partially esterified with chloroacetyl chloride and pyridine, yielding (?-4'-O-chloroacetyl-4'-O-demethyl-1-epipodophyllotoxin (III). The glycosidation of (III) with 2-(benzyloxocarbonylamino)-3-O-chloroacetyl-2-deoxy-4,6-O-ethylidene-beta-D-glucopyranose (IV) by means of BF3 ethearate in dichloromethane affords (?-1-O-[2-(benzyloxycarbonylamino)-3-O-chloroacetyl-2-deoxy-4,6-O-ethylidene-beta-D-glucopyranosyl]-4'-O-(chloroacetyl)-4'-O-demethyl-1-epipodophyllotoxin (?-(V) which, after separation of the diastereomers and elimination of the protecting groups with zinc acetate in refluxing methanol and H2 over Pd/C in ethyl acetate - ethanol, gives 1-O-(2-amino-2-deoxy-4,6-O-ethylidene-beta-D-glucopyranosyl)-4'-O-demethyl-1-epipodophyllotoxin (VI). Finally, this compound is methylated with formaldehyde and sodium cyanoborohydride in methanol. The sugar moiety has been obtained as follows: The reaction of 2-(benzyloxycarbonylamino)-2-deoxy-beta-D-glucopyranose (VII) with acetaldehyde and concentrated H2SO4 gives 2-(benzyloxycarbonylamino)-2-deoxy-4,6-O-ethylidene-beta-D-glucopyranose (VIII), which is then esterified with chloroacetyl chloride to (IV).

参考文献No.123468
标题:Studies on lignan lactone antitumor agents. II. Synthesis of N-alkylamino- and 2,6-dideoxy-2-aminoglycosidic lignan variants related to podophyllotoxin
作者:Saito, H.; Yoshikawa, H.; Nishimura, Y.; Kondo, S.; Takeuchi, T.; Umezawa, H.
来源:Chem Pharm Bull 1986,34(9),3741-46
合成路线图解说明:

The partial demethylation of (?-podophyllotoxin (I) with HBr in ether - dichloromethane, followed by alkaline hydrolysis with BaCO3 in aqueous acetone, gives (?-4'-O-demethyl-1-epipodophyllotoxin (II), which is partially esterified with chloroacetyl chloride and pyridine, yielding (?-4'-O-chloroacetyl-4'-O-demethyl-1-epipodophyllotoxin (III). The glycosidation of (III) with 2-(benzyloxocarbonylamino)-3-O-chloroacetyl-2-deoxy-4,6-O-ethylidene-beta-D-glucopyranose (IV) by means of BF3 ethearate in dichloromethane affords (?-1-O-[2-(benzyloxycarbonylamino)-3-O-chloroacetyl-2-deoxy-4,6-O-ethylidene-beta-D-glucopyranosyl]-4'-O-(chloroacetyl)-4'-O-demethyl-1-epipodophyllotoxin (?-(V) which, after separation of the diastereomers and elimination of the protecting groups with zinc acetate in refluxing methanol and H2 over Pd/C in ethyl acetate - ethanol, gives 1-O-(2-amino-2-deoxy-4,6-O-ethylidene-beta-D-glucopyranosyl)-4'-O-demethyl-1-epipodophyllotoxin (VI). Finally, this compound is methylated with formaldehyde and sodium cyanoborohydride in methanol. The sugar moiety has been obtained as follows: The reaction of 2-(benzyloxycarbonylamino)-2-deoxy-beta-D-glucopyranose (VII) with acetaldehyde and concentrated H2SO4 gives 2-(benzyloxycarbonylamino)-2-deoxy-4,6-O-ethylidene-beta-D-glucopyranose (VIII), which is then esterified with chloroacetyl chloride to (IV).

参考文献No.123470
标题:Syntheses of all four possible diastereomers of etoposide and its aminoglycosidic analogues via optical resolution of (?-podophyllotoxin by glucosidation with D- and L-sugars
作者:Saito, H.; Nishimura, Y.; Kondo, S.; Umezawa, H.
来源:Chem Lett 1987,5(5),799-802
合成路线图解说明:

The partial demethylation of (?-podophyllotoxin (I) with HBr in ether - dichloromethane, followed by alkaline hydrolysis with BaCO3 in aqueous acetone, gives (?-4'-O-demethyl-1-epipodophyllotoxin (II), which is partially esterified with chloroacetyl chloride and pyridine, yielding (?-4'-O-chloroacetyl-4'-O-demethyl-1-epipodophyllotoxin (III). The glycosidation of (III) with 2-(benzyloxocarbonylamino)-3-O-chloroacetyl-2-deoxy-4,6-O-ethylidene-beta-D-glucopyranose (IV) by means of BF3 ethearate in dichloromethane affords (?-1-O-[2-(benzyloxycarbonylamino)-3-O-chloroacetyl-2-deoxy-4,6-O-ethylidene-beta-D-glucopyranosyl]-4'-O-(chloroacetyl)-4'-O-demethyl-1-epipodophyllotoxin (?-(V) which, after separation of the diastereomers and elimination of the protecting groups with zinc acetate in refluxing methanol and H2 over Pd/C in ethyl acetate - ethanol, gives 1-O-(2-amino-2-deoxy-4,6-O-ethylidene-beta-D-glucopyranosyl)-4'-O-demethyl-1-epipodophyllotoxin (VI). Finally, this compound is methylated with formaldehyde and sodium cyanoborohydride in methanol. The sugar moiety has been obtained as follows: The reaction of 2-(benzyloxycarbonylamino)-2-deoxy-beta-D-glucopyranose (VII) with acetaldehyde and concentrated H2SO4 gives 2-(benzyloxycarbonylamino)-2-deoxy-4,6-O-ethylidene-beta-D-glucopyranose (VIII), which is then esterified with chloroacetyl chloride to (IV).

参考文献No.132978
标题:NK-611
作者:Prous, J.; Casta馿r, J.
来源:Drugs Fut 1991,16(2),113
合成路线图解说明:

The partial demethylation of (?-podophyllotoxin (I) with HBr in ether - dichloromethane, followed by alkaline hydrolysis with BaCO3 in aqueous acetone, gives (?-4'-O-demethyl-1-epipodophyllotoxin (II), which is partially esterified with chloroacetyl chloride and pyridine, yielding (?-4'-O-chloroacetyl-4'-O-demethyl-1-epipodophyllotoxin (III). The glycosidation of (III) with 2-(benzyloxocarbonylamino)-3-O-chloroacetyl-2-deoxy-4,6-O-ethylidene-beta-D-glucopyranose (IV) by means of BF3 ethearate in dichloromethane affords (?-1-O-[2-(benzyloxycarbonylamino)-3-O-chloroacetyl-2-deoxy-4,6-O-ethylidene-beta-D-glucopyranosyl]-4'-O-(chloroacetyl)-4'-O-demethyl-1-epipodophyllotoxin (?-(V) which, after separation of the diastereomers and elimination of the protecting groups with zinc acetate in refluxing methanol and H2 over Pd/C in ethyl acetate - ethanol, gives 1-O-(2-amino-2-deoxy-4,6-O-ethylidene-beta-D-glucopyranosyl)-4'-O-demethyl-1-epipodophyllotoxin (VI). Finally, this compound is methylated with formaldehyde and sodium cyanoborohydride in methanol. The sugar moiety has been obtained as follows: The reaction of 2-(benzyloxycarbonylamino)-2-deoxy-beta-D-glucopyranose (VII) with acetaldehyde and concentrated H2SO4 gives 2-(benzyloxycarbonylamino)-2-deoxy-4,6-O-ethylidene-beta-D-glucopyranose (VIII), which is then esterified with chloroacetyl chloride to (IV).

Drug Information Express,Drug R&D,Chemical Database,Patent Search.
Copyright © 2006-2024 Drug Future. All rights reserved.Contact Us