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Synthesis of a biotin-conjugate of phosmidosine O-ethyl ester as a G1 arrest antitumor drug |
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| Authors: | Sekine Mitsuo Okada Kazuhisa Seio Kohji Obata Tohru Sasaki Takuma Kakeya Hideaki Osada Hiroyuki |
| Affiliation: | aDepartment of Life Science, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan bCREST, JST (Japan Science and Technology Corporation), 4259 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan cFrontier Collaborative Research Center, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan dCancer Research Institute, Kanazawa University, Takara-machi, Kanazawa 920-8640, Japan eAntibiotics Laboratory, Discovery Research Institute, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan |
| Abstract: | 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. |
| Keywords: | Phosmidosine Structure–activity relationship 8-Oxoadenosine Antitumor activity Aminoacyl adenylate analog |
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