Applications of BOP reagent in solid phase synthesis. II: Solid phase side-chain to side-chain cyclizations using BOP reagent
Applications of BOP reagent in solid phase synthesis. II: Solid phase side-chain to side-chain cyclizations using BOP reagent
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DOI：
10.1111/j.1399-3011.1988.tb00028.x
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发表时间：
2009-01
期刊：
影响因子：
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通讯作者：
A. Felix;Ching-Tso Wang;E. Heimer;A. Fournier
中科院分区：
文献类型：
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作者：
A. Felix;Ching-Tso Wang;E. Heimer;A. Fournier
使用多种活化剂，进行动力学研究以评价在模型肽-树脂[Ala 15]-GRF（1-29）-BHA-树脂中Asp 3到Lys 12的固相侧链到侧链环化的速率。通过使用Nα-Boc氨基酸结合OFm/Fmoc侧链保护方案将Asp 3和Lys 12引入到肽链中。OFm和Fmoc侧链保护基显示对二异丙基乙胺稳定，并且在用DMF中的20%哌啶处理时选择性脱保护。使用苯并三唑-1-基-氧基-三（二甲基氨基）-磷鎓六氟磷酸盐（BOP试剂），固相侧链到侧链环化（内酰胺化）显示在2小时内进行完成，而使用DCC/HOBt，反应在24小时内仅完成55%。固相侧链到侧链环化的BOP程序不仅进行得更快，但也得到了一个更纯的环状产物。
Using a variety of activating agents, a kinetic study was carried out to evaluate the rate of solid phase side-chain to side-chain cyclization of Asp3 to Lys12 in the model peptide-resin, [Ala15]-GRF(1–29)-BHA-resin. Asp3 and Lys12 were introduced in the peptide chain by using Nα-Boc amino acids in conjunction with the OFm/Fmoc side-chain protection scheme. The OFm and Fmoc side-chain protecting groups were shown to be stable to diisopropylethylamine and selectively deprotected on treatment with 20% piperidine in DMF. Solid phase side-chain to side-chain cyclization (lactamization) was shown to proceed to completion within 2 h using benzotriazol-1-yl-oxy-tris(dimethylamino)-phosphonium hexafluorophosphate (BOP reagent) while the reaction was only 55% completed in 24h using DCC/HOBt. Solid phase side-chain to side-chain cyclization by the BOP procedure not only proceeded more rapidly but also gave a purer cyclic product.