Fmoc 保护膦酸假二肽的高效合成：用于合成基质金属蛋白酶抑制剂的砌块。
Efficient synthesis of Fmoc-protected phosphinic pseudodipeptides: Building blocks for the synthesis of matrix metalloproteinase inhibitors.
机构信息
Department of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton, FL 33431-0991, USA.
出版信息
Biopolymers. 2011;96(1):1-3. doi: 10.1002/bip.21425.
Abstract
A convenient route for the synthesis of Fmoc-protected phosphinic dipeptide building blocks is described. The protected amino acid isosteres benzyloxycarbonyl aminomethyl phosphinic acid (glycine surrogate), benzyl α-isopropyl acrylate (valine surrogate), and benzyl α-isobutyl acrylate (leucine surrogate) were synthesized starting from commercially available materials. Reaction of either the valine or leucine surrogate with bis(trimethylsilyl) phosphonite generated the pseudodipeptide bond. The synthesis concluded with an efficient one-pot three-step procedure involving a bis-deprotection of the N- and C-termini under catalytic hydrogenation conditions followed by selective capping of the N-terminus with an Fmoc group to yield either Fmoc-NHCH(2) PO(OAd)CH(2) CH(Pr(i) )CO(2) H or Fmoc-NHCH(2) PO(OAd)CH(2) CH(Bu(i) )CO(2) H.
摘要
描述了一种合成 Fmoc 保护膦酸二肽砌块的便捷路线。从商业可得的原料出发，合成了保护的氨基酸类似物苄氧羰基氨甲基膦酸（甘氨酸类似物）、苄基-α-异丙基丙烯酸酯（缬氨酸类似物）和苄基-α-异丁基丙烯酸酯（亮氨酸类似物）。将缬氨酸或亮氨酸类似物与双（三甲基硅基）亚膦酸酯反应生成假二肽键。该合成以高效的一锅三步法结束，该方法涉及在催化氢化条件下对 N-和 C-末端进行双脱保护，然后选择性地用 Fmoc 基团封端 N-末端，得到 Fmoc-NHCH(2)PO(OAd)CH(2)CH(Pr(i))CO(2)H 或 Fmoc-NHCH(2)PO(OAd)CH(2)CH(Bu(i))CO(2)H。
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