合成制备方法

将15 THF冷至-80℃，在氮气保护下加入2.82 L二异丙胺，再加入12L 15%丁基锂的己烷溶液，加入的速度保持反应液的温度为-75～-80℃。然后加入N，N’-二苯亚甲基鸟氨酸甲酯(I)溶于15L THF的溶液。加毕，缓慢升至35~40℃，并用一氯二氟甲烷鼓泡置换氮气，进行反应。加入20L饱和氯化钠溶液和75L异丙醚，分出有机层，水层提取。提取液和有机层合并，用饱和氯化钠溶液洗后，浓缩至剩油状物，即为化合物(Ⅱ)。该油状物和30 Llmol/L盐酸，在室温反应3h，进行水解。反应结束后，用氯仿提取，提取液废弃。经提取的水层用6L水稀释，调至Ph值3.3，加热，过滤，洗涤，重结晶，得依氟鸟氨酸。

用途

    用于非洲锥虫病(非洲睡眠病)。通过阻断锥虫属寄生虫增殖所必需的酶而起作用。

CHEMICAL IDENTIFICATION

RTECS NUMBER :

RM2981700

CHEMICAL NAME :

DL-Ornithine, 2-(difluoromethyl)-

CAS REGISTRY NUMBER :

67037-37-0

LAST UPDATED :

199612

DATA ITEMS CITED :

10

MOLECULAR FORMULA :

C6-H12-F2-N2-O2

MOLECULAR WEIGHT :

182.20

WISWESSER LINE NOTATION :

Z3XZVQYFF

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intracerebral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1364 ug/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

291 mg/kg/52W-I

TOXIC EFFECTS :

Behavioral - food intake (animal) Liver - changes in liver weight Blood - changes in platelet count

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

10 gm/kg

SEX/DURATION :

female 5-9 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

3952 mg/kg

SEX/DURATION :

female 5-8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) Reproductive - Effects on Embryo or Fetus - extra-embryonic structures (e.g., placenta, umbilical cord)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

24750 mg/kg

SEX/DURATION :

female 6-10 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

150 mg/kg

SEX/DURATION :

female 7 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

300 mg/kg

SEX/DURATION :

female 7 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - other measures of fertility

MUTATION DATA

TYPE OF TEST :

Cytogenetic analysis

TEST SYSTEM :

Rodent - hamster Kidney

DOSE/DURATION :

500 umol/L

REFERENCE :

HEREAY Hereditas (Lund, Sweden). (Gjoerloffsgatan 121, S-261 34 Landskrona, Sweden) V.1- 1947- Volume(issue)/page/year: 108,85,1988

毒理学数据：

1、急性毒性：大鼠（脑）LD50： 1,364μg/kg

分子结构数据

1、   摩尔折射率：38.73

2、   摩尔体积（cm³/mol）：140.8

3、   等张比容（90.2K）：362.2

4、   表面张力（dyne/cm）：43.7

5、   极化率（10^-24cm³）：15.35

计算化学数据

1.疏水参数计算参考值（XlogP）:-2.9

2.氢键供体数量:3

3.氢键受体数量:6

4.可旋转化学键数量:5

5.互变异构体数量:无

6.拓扑分子极性表面积89.3

7.重原子数量:12

8.表面电荷:0

9.复杂度:166

10.同位素原子数量:0

11.确定原子立构中心数量:0

12.不确定原子立构中心数量:1

13.确定化学键立构中心数量:0

14.不确定化学键立构中心数量:0

15.共价键单元数量:1