Vanderhaeghe H, Thomis J
J Med Chem. 1975 May;18(5):486-90. doi: 10.1021/jm00239a009.
Cycloaddition of azidoacetyl chloride to benzyl D-5,5-dimethyl-5-phenyl-2-thiazoline-4-carboxylate (1a) gave 5-phenyl-6alpha-azidopenicillanate (2a). By catalytic reduction of 2a and reaction with phenoxyacetyl chloride, 5-phenyl-6-epiphenoxymethylpenicillin benzyl ester (4a) was obtained. Oxidation of 4a gave the sulfoxide 6, which was isomerized in the presence of DBN. The sulfoxide 7 with the normal configuration could be isolated but deoxygenation of the sulfoxide was not successful. Isomerization of 4a with DBN, either with or without silylation of the side chain, gave a mixture from which 5-phenylphenoxymethylpenicillin benzyl ester (5) was isolated. Compound 5 was debenzylated to 5-phenylphenoxymethylpenicillin potassium salt (8). The antibacterial activity of 8 was low, whereas the 6-epimer 9 was inactive. Contary to published information, the 5-phenylpenam derivative 4c could be prepared by the same method.
叠氮乙酰氯与苄基 D-5,5-二甲基-5-苯基-2-噻唑啉-4-羧酸酯（1a）进行环加成反应得到 5-苯基-6α-叠氮青霉酸酯（2a）。通过对 2a 进行催化还原并与苯氧乙酰氯反应，得到 5-苯基-6-表苯氧甲基青霉素苄酯（4a）。4a 的氧化得到亚砜 6，其在 DBN 存在下发生异构化。具有正常构型的亚砜 7 可以分离出来，但亚砜的脱氧反应未成功。4a 在有或没有侧链甲硅烷基化的情况下用 DBN 异构化，得到一种混合物，从中分离出 5-苯基苯氧甲基青霉素苄酯（5）。化合物 5 脱苄基得到 5-苯基苯氧甲基青霉素钾盐（8）。8 的抗菌活性较低，而 6-差向异构体 9 无活性。与已发表的信息相反，5-苯基青霉烷衍生物 4c 可以通过相同的方法制备。
