Pancratistatin cyclic phosphate prodrugs and phenpanstatin...

Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...

Reexamination Certificate

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C546S048000, C546S065000, C544S125000, C544S361000

Reexamination Certificate

active

10561338

ABSTRACT:
Selective phosphorylation of phenpanstatin (3a) with tetrabutylammonium dihydrogen phosphate and dicyclohexyl-carbodiimide in pyridine followed by cation exchange chromatographic procedures was found to provide an efficient mute to a new series (3b-3d) of promising 3,4-O-cyclic phosphate prodrugs designated phenpanstatin phosphates. Application of analogous reaction conditions to pancratistatin (1a) led to a mixture of monophosphate derivatives where sodium paancratistatin 4-O-phosphate (4a) was isolated and the structure confirmed by x-ray craxtallography. Modification of the reaction conditions allowed direct phosphorylation of pancratistatin followed by cation exchange chromatography to afford sodium pancratistatin 3,4-O-cyclic phosphate (5b) which was selected for preclinical development.

REFERENCES:
patent: WO 02/50023 (2002-06-01), None
International Search Report for PCT/US04/19725 dated Jan. 11, 2005.
Written Opinion of the International Search Authority for PCT/US04/19725 dated Jan. 11, 2005.
Pettit et al., “Antineoplastic Agents. 511. Direct Phosphorylation of Phenpanstatin and Pancratistatin”,J. Nat. Prod., 67:322-327, (2004).

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