The syntheses of the Fmoc-protected Peptide Nucleic Acid (PNA) monomer pentafluorophenyl esters of adenine (26), cytosine (23), guanine (29) and thymine (20), and their oligomerization are described. The Fmoc PNA backbone 1 is prepared as a stable hydrochloride salt. The base acetic acids of adenine (4) and cytosine (3) were prepared by Cbz protection of the exocyclic amino groups followed by alkylation with t-butylbromoacetate and subsequent acid hydrolysis of the t-butyl ester. Allylation of 6-chloro-2-aminopurine followed by acid hydrolysis, Cbz protection with N-(benzyloxycarbonyl)imidazole, ozonolytic cleavage, and oxidation afforded the Cbz-protected guanine acetic acid (5). The base acetic acids (2, 3, 4 and 5) were coupled to the backbone (1) with either EDC (2 and 3) or BOP reagent (4 and 5). Acid hydrolysis of the resulting t-butyl esters and transesterification afforded the corresponding pentafluorophenyl esters (20, 23, 26 and 29). Oligomerization is conducted on a 0.05 mmol scale with a mere 2 fold excess of monomer in each coupling cycle. The N-terminal Fmoc group is retained on the final oligomer, following HF cleavage and deprotection, providing a convenient lipophilic handle for HPLC purification.

中文翻译：

---

Fmoc介导的肽核酸合成

描述了腺嘌呤（26），胞嘧啶（23），鸟嘌呤（29）和胸腺嘧啶（20）的Fmoc保护的肽核酸（PNA）单体五氟苯基酯的合成及其低聚反应。Fmoc PNA主链1制备为稳定的盐酸盐。腺嘌呤（的基乙酸4）和胞嘧啶（3）是由环外氨基随后烷基化的Cbz基保护以制备吨-butylbromoacetate和随后的酸水解吨丁基酯。对6-氯-2-氨基嘌呤进行烯丙基化，然后进行酸水解，用N进行Cbz保护-（苄氧基羰基）咪唑，经臭氧分解和氧化得到Cbz-保护的鸟嘌呤乙酸（5）。用EDC（2和3）或BOP试剂（4和5）将基础乙酸（2、3、4和5）偶联到主链（1）。所得叔丁基酯的酸水解和酯交换反应得到相应的五氟苯基酯（20、23、26和29）。在每个偶联循环中，仅以过量的2倍的单体，以0.05 mmol的规模进行低聚。该ñ在HF裂解和脱保护之后，末端Fmoc基团保留在最终的低聚物上，为HPLC纯化提供了方便的亲脂性处理。