Bernard Julie, Malacea-Kabbara Raluca, Clemente Gonçalo S, Burke Benjamin P, Eymin Marie-Joëlle, Archibald Stephen J, Jugé Sylvain
†Institut de Chimie Moléculaire de l'Université de Bourgogne (ICMUB) StéréochIM UMR CNRS 6302, 9 Avenue A. Savary BP 47870, 21078 Dijon Cedex, France.
‡Department of Chemistry and Positron Emission Tomography Research Centre, University of Hull, Cottingham Road, Hull, East Yorkshire HU6 7RX, United Kingdom.
J Org Chem. 2015 May 1;80(9):4289-98. doi: 10.1021/acs.joc.5b00246. Epub 2015 Apr 14.
The synthesis of o-boronato- and o-trifluoroborato-phosphonium salts supported by the L-amino acid side chain is described. The synthesis of these new class of amino acid derivatives was achieved by stereoselective quaternization of o-(pinacolato)boronatophenylphosphine with β- or γ-iodo amino acid derivatives which are prepared from L-serine or L-aspartic acid, respectively. The quaternization of the phosphine was performed using either iodo amino ester or carboxylic acid derivatives. In addition, free carboxylic acid and amine derivatives were obtained by saponification or HCl acidolysis of o-boronato-phosphonium amino esters, respectively. The usefulness of these compounds in peptide coupling was demonstrated by coupling an o-boronato-phosphonium amino ester with an aspartic acid moiety. When the o-boronato-phosphonium amino acid or dipeptide derivatives were mixed with fluoride, the corresponding o-trifluoroborated products were cleanly and rapidly obtained in high isolated yields. The hydrolysis of these compounds at room temperature using a phosphate buffer pH 7/CD3CN mixture has shown only traces of free fluoride F(-) after several days. Finally, a preliminary radiolabeling essay has proven the facile [(18)F]-fluoride incorporation and high stability of the radiolabeled product in aqueous conditions. Indeed, this new class of boron-phosphonium amino acid derivatives shows promising properties for their applications in synthesis and labeling of peptides.
本文描述了由L-氨基酸侧链支撑的邻硼酸盐和邻三氟硼酸盐鏻盐的合成。这些新型氨基酸衍生物的合成是通过邻（频哪醇硼酸酯）硼苯基膦与分别由L-丝氨酸或L-天冬氨酸制备的β-或γ-碘代氨基酸衍生物进行立体选择性季铵化反应来实现的。膦的季铵化反应使用碘代氨基酸酯或羧酸衍生物进行。此外，分别通过邻硼酸盐鏻氨基酸酯的皂化或HCl酸解得到游离羧酸和胺衍生物。通过将邻硼酸盐鏻氨基酸酯与天冬氨酸部分偶联，证明了这些化合物在肽偶联中的实用性。当邻硼酸盐鏻氨基酸或二肽衍生物与氟化物混合时，相应的邻三氟硼酸盐产物能以高分离产率干净、快速地得到。使用pH 7的磷酸盐缓冲液/CD3CN混合物在室温下对这些化合物进行水解，几天后仅显示出痕量的游离氟离子F(-)。最后，一项初步的放射性标记实验证明了[(18)F]-氟化物的轻松掺入以及放射性标记产物在水性条件下的高稳定性。实际上，这类新型硼-鏻氨基酸衍生物在肽的合成和标记应用中显示出有前景的性质。
