Journal of Pharmaceutical Sciences p. 393 - 398 (1995)
Update date:2022-08-17
Topics:
Ludeman
Shulman-Roskes
Wong
Han
Anderson
Strong
Colvin
There is ongoing interest in the selective, quantitative analysis of the cyclophosphamide metabolites 4-hydroxycyclophosphamide (2a) and aldophosphamide (3a) because these tautomers are generally believed to play a key role in oncostatic selectivity and metabolite transport. O-(2,3,4,5,6- Pentafluorobenzyl)hydroxylamine (C6F5CH2ONH2, 1 equiv) provided for the complete conversion (by 31P NMR, 60% reaction within 15 min at 20 °C) of 2a/3a (17 mM in H2O/CH3OH) to E/Z-aldophosphamide O-(2,3,4,5,6- pentafluorobenzyl)oxime [C6F5CH2ON=CHCH2CH2OP-(O)(NH2)N(CH2CH2Cl)2; E:Z = 54:46 (±3% average deviation)]. Under these conditions, the oxime exhibited little (6%) decomposition over 3 weeks. Parallel studies showed that 4-hydroxyifosfamide/aldoifosfamide reacted completely to give the analogous aldoifosfamide oxime [C6F5- CH2ON=CHCH2CH2OP(O)(NHCH2CH2Cl)2; E:Z = 52:48 (±1% average deviation)] with 50% reaction within 15 min at 20 °C with no product decomposition over 3 weeks. In aqueous methanol and with 2 equiv C6F5CH2ONH2, clinically useful 4-hydroperoxycyclophosphamide (10 mM; τ = 10 min, 37 °C) and its isomer 4-hydroperoxyifosfamide (10 mM; τ = 25 min, 20 °C) underwent complete conversion to the corresponding aldehyde oximes. Each oxime was synthesized with deuterium in the chloroethyl moieties for use as internal standards in GC/MS applications.
View MoreContact:+86-731-84427351
Address:154 JIANXIANG SOUTH ROAD
Shanghai KFSL Pharmaceutical Technology Co.,Ltd.
Contact:+86-21-39971718
Address:859 jiadingchengliu shanghai
SHANGHAI SYSTEAM BIOCHEM CO., LTD
website:http://www.systeambc.com
Contact:86-021-58380978
Address:Building 87,Lane 669, Dong Jing Road Shanghai,P.R.China
ZhangJiaGang YaRui Chemical Co.,Ltd.
Contact:0512-58360968
Address:China JiangSu Province Zhang Jia Gang City YangShe Oriental Plaza Building 10 B307
Chengdu Sino-Strong Pharmaceutical Co.,Ltd.
website:http://www.sino-strong.com.cn
Contact:+86-28-82666753
Address:459 West haike road,Cross-straits technological industry park, Wenjiang district,Chengdu, P.R.China
Doi:10.1021/jacs.0c02707
(2020)Doi:10.1016/j.ejmech.2016.11.045
(2017)Doi:10.1016/j.tet.2016.03.039
(2016)Doi:10.1039/c9ra01636h
(2019)Doi:10.1007/BF02494277
(1998)Doi:10.1016/S1386-1425(02)00142-7
(2003)