Ward D E, Gai Y, Lazny R, Pedras M S
Department of Chemistry, University of Saskatchewan, 110 Science Place, Saskatoon SK S7N 5C9, Canada.
J Org Chem. 2001 Nov 16;66(23):7832-40. doi: 10.1021/jo015953+.
The syntheses of the host-selective phytotoxin destruxin B [cyclo(betaAla-Hmp-Pro-Ile-MeVal-MeAla), Hmp = (2R)-2-hydroxy-4-methylpentanoic acid], and the closely related natural analogues homodestruxin B (MeVal-->MeIle), desmethyldestruxin B (MeVal-->Val), hydroxydestruxin B (Hmp-->Dhmp, Dhmp = (2R)-2,4-dihydroxy-4-methylpentanoic acid), and hydroxyhomodestruxin B (MeVal-->MeIle, Hmp-->Dhmp) are described. In each case, the MeAla-betaAla linkage was formed by cyclization and the precursor linear hexadepsipeptides were formed by condensing two three-residue fragments. Radiolabeled samples of destruxin B, homodestruxin B, and hydroxydestruxin B were prepared by coupling [3-(14)C]-beta-alanine to the appropriate pentadepsipeptide followed by cyclization. A noteworthy feature of the synthesis involves the novel use of a Boc-hydrazide protecting group on dipeptides with a C-terminal N-methylalanine residue to inhibit the otherwise facile dioxopiperazine formation during peptide coupling.
宿主选择性植物毒素毁灭菌素B [环（β-丙氨酸-Hmp-脯氨酸-异亮氨酸-甲基缬氨酸-甲基丙氨酸），Hmp =（2R）-2-羟基-4-甲基戊酸]以及密切相关的天然类似物高毁灭菌素B（甲基缬氨酸→甲基异亮氨酸）、去甲基毁灭菌素B（甲基缬氨酸→缬氨酸）、羟基毁灭菌素B（Hmp→Dhmp，Dhmp =（2R）-2,4-二羟基-4-甲基戊酸）和羟基高毁灭菌素B（甲基缬氨酸→甲基异亮氨酸，Hmp→Dhmp）的合成方法已被描述。在每种情况下，甲基丙氨酸-β-丙氨酸键通过环化形成，前体线性六缩肽通过两个三残基片段缩合形成。毁灭菌素B、高毁灭菌素B和羟基毁灭菌素B的放射性标记样品通过将[3-（14）C]-β-丙氨酸与适当的五缩肽偶联，然后环化来制备。该合成的一个显著特点是在具有C末端N-甲基丙氨酸残基的二肽上新颖地使用了Boc-酰肼保护基团，以抑制肽偶联过程中原本容易发生的二氧哌嗪形成。
