Synthesis of a biotin-conjugate of phosmidosine O-ethyl ester as a G1 arrest antitumor drug.
This paper deals with the synthesis of a stable biotin-phosmidosine conjugate molecule 3 that is required for isolation of biomolecules that bind to phosmidosine (1). It was found that introduction of a biotin residue into the 6-N position of phosmidosine could be carried out by reaction of an N7-Boc-7,8-dihydro-8-oxoadenosine derivative 13 with phenyl chloroformate followed by displacement with a diamine derivative 6 along with the simultaneous removal of the Boc group and one of the two phenoxycarbonyl groups and the successive condensation with an N-tritylated biotin derivative 5. The condensation of an N-prolylphosphorodiamidite derivative 4 with an appropriately protected 7,8-dihydro-8-oxoadenosine derivative 17 having the biotin residue gave the coupling product 18, which was deprotected to give the biotin-phosmidosine (O-ethyl ester) conjugate 3.
Sekine
Mitsuo
M
Department of Life Science, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan. msekine@bio.titech.ac.jp
Okada
Kazuhisa
K
Seio
Kohji
K
Obata
Tohru
T
Sasaki
Takuma
T
Kakeya
Hideaki
H
Osada
Hiroyuki
H
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001710:Biotin / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D011685:Purine Nucleotides / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D011685:Purine Nucleotides; C500514:biotin-phosmidosine (O-ethyl ester) conjugate; C068885:phosmidosine; D001710:Biotin