Modification of C-terminal peptides to form peptide enamides: Synthesis of chondriamides A and C
Modification of C-terminal peptides to form peptide enamides: Synthesis of chondriamides A and C
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DOI：
10.1021/jo0158027
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发表时间：
2001-11-30
影响因子：
3.6
通讯作者：
Porco, JA
中科院分区：
文献类型：
--
作者：
Wang, X;Porco, JA
Enamides have been studied extensively as synthons in organic synthesis and have been used prominently in the preparation of heterocycles1 and in asymmetric synthesis. 2 These functional groups are stable under neutral or basic conditions, but with Brønsted acids, they undergo protonation to form N-acyliminium ions that may react with oxygen, sulfur, or π-based nucleophiles. 3 Recently, there has been renewed interest in the synthesis of enamides due to the isolation and potent antitumor activity of the salicylate antitumor macrolides (cf. oximidine II4 (1) and salicylihalamides A5 (2) and B (3), Figure 1), which contain highly unsaturated enamide side chains. As part of a general program toward the synthesis of enamide-containing natural products, we recently reported the synthesis of enamides related to the salicylate antitumor macrolides lobatamides6 and oximidines4 using copper (I)-carboxylate-catalyzed substitution of vinyl iodides and amides. 7 An additional class of bioactive enamide natural products that has attracted our attention are the linear and cyclic peptide enamides, representative members of which are shown in Figure 1. Frangufoline (4) is a cyclopeptide alkaloid8 with sedative and antiinflammatory properties that has been reported to bind to multiple sites on calmodulin. 9Chondriamide A (5) shows cytotoxicity against KB and LOVO cells and antiviral activity against HSV II. 10 Chondriamide C (6) is a bis-indole-containing marine natural product that shows both cytotoxicity and anthelmintic activity. 11 Terpeptin (7) is a novel peptide recently isolated from Aspergillus terreus that inhibits the cell cycle at the G2/M phase. 12 Due to the presence of numerous amide functional groups in these molecules, we considered alternatives to vinyl halide amidation7 developed in our laboratories to access natural and unnatural compounds in this class. Since all of the compounds contain unsaturated enamides derived from aromatic amino acid residues, we reasoned that modification of C-terminal peptides by an oxidative decarboxylationelimination process could be implemented to produce natural and unnatural peptide enamides from readily available peptide precursors (Figure 2). The overall (and possibly biomimetic) process is analogous to known enzymatic posttranslational, oxidative decarboxylation reactions such as the EpiD flavoprotein-catalyzed oxidative decarboxylation of peptidyl cysteines. 13 Although decarboxylation of dehydroamino acids has been utilized to prepare enamides14 and-elimination reactions have been used to produce enamides and related compounds, 15 synthesis of peptide enamides from tandem oxidative decarboxylation-elimination of C-terminal amino acids is underdeveloped. 16 Herein, we report general protocols for the synthesis of peptide enamides from C-terminal peptides and application of this methodology to the synthesis of the cytotoxic indole-enamide natural products chondriamides A and C.
