Felix A M, Jimenez M H, Mowles T, Meienhofer J
Int J Pept Protein Res. 1978 May;11(5):329-39.
To exemplify the extension to synthesis of sulfur-containing peptides of the Nalpha-benzyloxycarbonyl and side chain tert-butyl protective group combination, somatostatin has been synthesized via incremental chain elongation starting from the COOH-terminal cysteine. Cleavage of the Nalpha-benzyloxycarbonyl groups was achieved in high yield, at each stage, by palladium-catalyzed hydrogenation in liquid ammonia. All side chain functionalities including the cysteine thiol groups were blocked by tert-butyl-derived groups. Each gave rise to individual n.m.r. signals which permitted sensitive characterization of all intermediate protected peptides. Mild conditions were used for the removal of all protecting groups from the completed somatostatin tetradecapeptide. The tert-butyl thiol protective groups were readily and completely cleaved by mercuric acetate at pH 4. Oxidation of dihydrosomatostatin with potassium ferricyanide provided somatostatin in good yield. The results indicate that the absolute selectivity between alpha-amine and side chain protective group cleavage afforded by Nalpha-benzyloxycarbonyl hydrogenolysis in the presence of omega-tert-butyl groups may now be extended to synthesis of cysteine- and methionine-containing peptides.
为了举例说明将Nα-苄氧羰基和侧链叔丁基保护基团组合扩展至含硫肽的合成，已从COOH末端半胱氨酸开始通过逐步链延长法合成了生长抑素。在每个阶段，通过在液氨中钯催化的氢化反应，以高产率实现了Nα-苄氧羰基的裂解。包括半胱氨酸硫醇基团在内的所有侧链官能团均被叔丁基衍生基团封闭。每个基团都产生了单独的核磁共振信号，从而能够对所有中间保护肽进行灵敏的表征。使用温和的条件从完整的生长抑素十四肽上去除所有保护基团。叔丁基硫醇保护基团在pH 4时很容易被乙酸汞完全裂解。用铁氰化钾氧化二氢生长抑素可高产率地得到生长抑素。结果表明，在ω-叔丁基存在下，Nα-苄氧羰基氢解在α-胺和侧链保护基团裂解之间提供的绝对选择性现在可扩展至含半胱氨酸和蛋氨酸肽的合成。
