Vere Hodge R A, Darlison S J, Readshaw S A
SmithKline Beecham Pharmaceuticals, Epsom, Surrey, England.
Chirality. 1993;5(8):577-82. doi: 10.1002/chir.530050803.
Famciclovir is the oral form of the potent antiherpesvirus agent, penciclovir. Hydrolysis of one of the acetyl ester groups of famciclovir creates a chiral centre leading to the possible formation of (R)- and (S)-enantiomers. During its conversion to penciclovir, famciclovir forms two chiral metabolites, namely monoacetyl-6-deoxy-penciclovir and monoacetyl-penciclovir. The absolute configuration and stereospecificity of the monoacetyl metabolites of famciclovir, produced in human intestinal wall extract, were determined using isotopically chiral famciclovir and 13C NMR spectroscopy of the isolated metabolites. 13C NMR showed that the esterase(s), in human intestinal wall extract, hydrolysed the acetyl group preferentially from the pro-(S)-acetoxymethyl group of famciclovir. The specificity of esterase action in forming monoacetyl-6-deoxy-penciclovir and monoacetyl-penciclovir was about 77 and 72%, respectively.
泛昔洛韦是强效抗疱疹病毒药物喷昔洛韦的口服剂型。泛昔洛韦的一个乙酰酯基团水解会产生一个手性中心，导致可能形成（R）-和（S）-对映体。在转化为喷昔洛韦的过程中，泛昔洛韦形成两种手性代谢物，即单乙酰-6-脱氧喷昔洛韦和单乙酰喷昔洛韦。使用同位素手性泛昔洛韦和分离代谢物的13C NMR光谱法，测定了人肠壁提取物中产生的泛昔洛韦单乙酰代谢物的绝对构型和立体特异性。13C NMR表明，人肠壁提取物中的酯酶优先从泛昔洛韦的前-（S）-乙酰氧基甲基基团水解乙酰基。酯酶作用形成单乙酰-6-脱氧喷昔洛韦和单乙酰喷昔洛韦的特异性分别约为77%和72%。
