Direct palladium-mediated on-resin disulfide formation from Allocam protected peptides.
Direct palladium-mediated on-resin disulfide formation from Allocam protected peptides.
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DOI：
10.1039/c7ob00536a
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发表时间：
2017-04-05
影响因子：
3.2
通讯作者：
Stockdill JL
中科院分区：
文献类型：
--
作者：
Kondasinghe TD;Saraha HY;Odeesho SB;Stockdill JL
含二硫化物的多肽的合成代表了肽化学中的长期挑战，并且用于构建二硫化物的广泛适用的方法是持续需求的。很少有策略存在直接从其保护的对应物在树脂上形成二硫化物。我们在此提出了一种新的策略，直接从Allocam保护的半胱氨酸的二硫化物树脂建设。我们的钯介导的方法是温和的，使用现成的试剂，不需要特殊的设备。未观察到还原的肽中间体或S-烯丙基化产物，并且在最终产物中未检测到残留钯。通过催产素的C-羧基类似物的合成证明了这种方法的实用性。我们提出了一种温和，方便的方法，用于在固体支持物上将Allocam保护的肽直接转化为含二硫键的保护肽。
The synthesis of disulfide-containing polypeptides represents a long-standing challenge in peptide chemistry, and broadly applicable methods for the construction of disulfides are in constant demand. Few strategies exist for on-resin formation of disulfides directly from their protected counterparts. We present herein a novel strategy for the on-resin construction of disulfides directly from Allocam-protected cysteines. Our palladium-mediated approach is mild and uses readily available reagents, requiring no special equipment. No reduced peptide intermediates or S-allylated products are observed, and no residual palladium can be detected in the final products. The utility of this method is demonstrated through the synthesis of the C-carboxy analog of oxytocin. We present a mild, convenient method for direct conversion of Allocam protected peptides to disulfide-containing protected peptides on solid support.