鎝環丁基丙烯胺肟非鏡像立體異構物合成路徑與影響因子之探討
鎝環丁基丙烯胺肟非鏡像立體異構物
合成路徑與影響因子之探討
蔡長書
慈濟技術學院放射技術系暨放射醫學科學研究所
提要
本研究以六甲基丙烯胺肟（propyl amine oxine）之6,6-環丁基取代基之鎝-99 氧錯合
物，探討放射性鎝核醫藥物（radiopharmaceuticals）配位子不同丙烯胺肟衍生物之非鏡
像立體異構物之配位子合成路徑及其立體化學品質。首先利用有機合成法製備環丁基丙
烯胺肟系列衍生物（propyl amine oxine derivatives）非鏡像立體異構物，並以多次分步
再結晶法作有效分離d,l-型、meso-型及非晶成份之立體異構物，另以熱分析法之微差掃
瞄卡計（DSC）進行熔點之測定。在鎝錯合物製備方面，以取代途徑、還原途徑兩種不
同合成路徑（synthetical route）評估鎝核醫藥物不同環丁基丙烯胺肟衍生物配位子非鏡
像立體異構物之相關品質與影響因子。評估因素包含合成產率、立體化學純度、鎝錯合
反應及鎝核構形等。由實驗結果可知，以取代途徑（substitution route）合成路徑法合成
99 TcO-d,1-CB-PAO 與99 TcO-meso-CB-PAO 兩者產率約為0 %（n＝10）與傳統鎝核醫藥
物或丙烯胺肟相關製備法大異其趣，推測原因可能與鎝核的構形及分子大小與形狀，及
其立體化學結構有關，尤其CB-PAO 配位子在有機溶劑中顯現其高脂溶性，而較不具離
子性質，故無法利用傳統離子交換方式形式有效進行鎝錯合反應。以還原途徑（reduction
route）合成路徑法合成99 TcO-d,1-CB-PAO 與99 TcO-meso-CB-PAO 兩者產率分別為30
∼40 %及60∼80 %（n＝10）。以不同立體異構物樣品0.5~3.0 mg 進行熱分析法之微差
掃瞄卡計測定結果得知，經純化之d,1-CB-PAO 熔點約為116.7±1℃，而由純度推估，約
含3∼5 % meso-CB-PAO 不純物；經純化之meso-CB-PAO 熔點約為159.7±1℃。經
1H-NMR 及13C-NMR 鑑定，99TcO-d,1-CB-PAO 與99 TcO-meso-CB-PAO 兩者皆具有高立
體化學純度。
關鍵字：鎝-99 錯合物、非鏡像立體異構物、鎝核構形、取代途徑、還原途徑
Study on the synthetical routes and influence factors of
Tc(V)O-cyclobutyl propyl amine oxine diastereoisomers
Chang-Shu Tsai
Department of Radiological Technology and Institute of Radiological Science,
Tzu-Chi College of Technology
Abstract
Propylene amine oxine oxo-technetium(V) complexes [Tc(V)O-cyclobutyl propylene
amine oxine ；Tc(V)O-CB-PAO] were prepared and their characteristic properties of synthetic
routes and influence factors were studied thoroughly. The CB-PAO diastereoisomers were
synthesized and separated by recrystallization. The melting points of ligands were measured
by DSC. Synthesis of 99Tc(V)O-CB-PAO through reduction route were compared with that of
substitution route. The influence factors of Tc(V)O-cyclobutyl propyl amine oxine
diastereoisomers were also evaluated by chemical yield, stereochemical purity, Tc-complexes
reaction and TcO-core configulations. All compounds obtained in this study were examined by
EA, FAB-MASS spectrometry, NMR spectroscopy to insure the qualities.
Both 99Tc(V)O-d,l-CB-PAO and 99Tc(V)O-meso-CB-PAO are high stereochemical
purities by 1H-NMR and 13C-NMR spectroscopy. They are also electrically neutral, and highly
lipophilic. The chemical yieldis about 60~80 % for meso-form TcO-CB-PAO，and 30~40 %
for d,l-form TcO-CB-PAO. However, it must be pointed out that the chemical yields for both
TcO-CB-PAO complexes are ca. 0 % by substitution routes. The reasons may be related with
some influence factors including TcO-core configulation, Tc-complexes size and their
stereochemical structures. Expecially, the properties of CB-PAO ligands are more lipophilic, it
may be difficult to form Tc-complexes through the ion-exchange reaction as conventional
preparation.
Keywords：Technetium-99-complexes, diastereoisomers, TcO-core configulation, reduction
route, substitution route
