S-[2-(叔丁氧羰基氨基)乙基]-3-苯基丙酸硫酯类化合物脱除Boc保护基的反应研究

Study on the Deprotection of Boc Group of S-2-(tert-Butoxycarbonylamino)ethyl 3-Phenylpropanethioates

报道了取代苯丙酸类化合物1a～1d与N-叔丁氧羰基-L-半胱氨酸甲酯(2)在双(2-氧代-3-噁唑烷基)次磷酰氯(BOP-C1)作用下,以79%～92%收率得到缩合产物S-[2-(叔丁氧羰基氨基)乙基]-3-苯基丙酸硫酯类化合物3a～3d;3a～3d在三氟乙酸(TFA)作用下脱除Boc保护基时,结果不仅得到了正常的脱保护基产物4a～4d,还生成了2-取代噻唑啉类化合物5a～5d,研究表明5a～5d是由4a～4d分子内脱水环合而成.通过优化三氟乙酸用量、反应温度以及反应时间等条件,能够以较高收率分别得到4a～4d和5a～5d(收率85%～91%和86%～89%).而S-[2-(叔丁氧羰基氨基)乙基]-3-苯基丙烯酸硫酯类化合物3e～3f由于双键结构,在三氟乙酸作用下仅生成脱除Boc保护基产物4e～4f.该反应的研究为2-取代噻唑啉类化合物的合成提供了一种简便有效的方法.

S-2-（tert-Butoxycarbonylamino）ethyl 3-phenylpropanethioates （3a-3d） were synthesized in 79%-92% yields through the esterification of substituted 3-phenylpropanoic acids （1a-1d） and methyl N-（tert-butoxycarbonyl）-L-cysteine （2） by using bis（2-oxo-3-oxazolidinyl）phosphinic chloride （BOP-Cl） as the condensation agent. The deprotection of Boc group of 3a-3d by trifluoroacetic acid （TFA） gave not only normal deprotecting products 4a-4d but also 2-substituted thiazolines 5a-5d which were obtained by intramolecular dehydration of the corresponding 4a-4d, whereas the deprotection of Boc group of S-2-（tert-butoxycarbonylamino）ethyl 3-phenylpropenethioates （3e-3f） afforded only deprotecting products 4e-4f under the same condition due to their double bond rigid structures. 4a-4d and 5a-5d could be obtained in high yields （85%-91% and 86%-89%） respectively by optimizing reaction conditions on the amount of TFA, the reaction temperature and time, which provided a facile and effective method to synthesize 2-substituted thiazolines.