Kahalalide F, the only member of the family of peptides called kahalalides, isolated from the sacoglossan mollusc Elysia rufescens and the green alga Bryopsis sp., with important bioactivity, is in clinical trials for treatment of prostate cancer. An efficient solid-phase synthetic approach is reported. Kahalalide F presents several synthetic difficulties: (i) an ester bond between two β-branched and sterically hindered amino acids; (ii) a didehydroamino acid; and (iii) a rather hydrophobic sequence with two fragments containing several β-branched amino acids in a row, one of them terminated with a saturated aliphatic acid. The cornerstones of our strategy were (i) a quasiorthogonal protecting system with allyl, tert-butyl, fluorenyl, and trityl-based groups, (ii) azabenzotriazole coupling reagents, (iii) formation of the didehydroamino acid residue on the solid phase, and (iv) cyclization and final purification in solution. HPLC, high-field NMR, and biological activity studies showed that the correct st...

中文翻译：

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Kahalalide F1,2的合成与结构测定

Kahalalide F 是称为 kahalalides 的肽家族的唯一成员，从 sacoglossan 软体动物 Elysia rufescens 和绿藻 Bryopsis sp. 中分离出来，具有重要的生物活性，正在临床试验中用于治疗前列腺癌。报道了一种有效的固相合成方法。Kahalalide F 存在几个合成困难：(i) 两个 β-支链和空间位阻氨基酸之间的酯键；(ii) 二脱氢氨基酸；(iii) 一个相当疏水的序列，其中两个片段连续含有几个 β-支链氨基酸，其中一个片段以饱和脂肪酸终止。我们策略的基石是 (i) 具有烯丙基、叔丁基、芴基和三苯甲基基团的准正交保护系统，(ii) 氮杂苯并三唑偶联剂，(iii) 在固相上形成双脱氢氨基酸残基，以及 (iv) 在溶液中环化和最终纯化。HPLC、高场核磁共振和生物活性研究表明，正确的...