一种基于螺异恶唑啉脯氨酸的氨基酸支架，用于固相和单珠单化合物库的合成。

A spiroisoxazolinoproline-based amino acid scaffold for solid phase and one-bead-one-compound library synthesis.

作者信息

Dixon Seth M, Milinkevich Kristin A, Fujii Jeffrey, Liu Ruiwu, Yao Nianhuan, Lam Kit S, Kurth Mark J

机构信息

Department of Chemistry, University of California, One Shields Avenue, Davis, California 95616, USA.

出版信息

J Comb Chem. 2007 Jan-Feb;9(1):143-57. doi: 10.1021/cc060090p.

DOI:10.1021/cc060090p

PMID:17206843

Abstract

An efficient, multigram synthesis of a spiroisoxazolinoproline-based amino acid, 7, requiring minimal purification, delivering good cis:trans diastereoselectivity (approximately 1:4), and providing good yields is reported. Surface-bound studies of the reduction of an arylnitro group in the presence of an isoxazoline ring with tin(II) dichloride dihydrate were undertaken to confirm the stability of the isoxazoline ring. Full derivitization of this spiroisoxazolinoproline-based amino acid scaffold was performed during the synthesis of a sample library with high yields and high purity that validated the efficiency of the chemistry that was employed in resin-bound library synthesis. A 129,600 member one-bead-one-compound (OBOC) library based on the scaffold 7 was synthesized utilizing a dual amino acid encoding method and bifunctionalization of TentaGel resin.

摘要

报道了一种高效、多克级合成基于螺异恶唑啉脯氨酸的氨基酸7的方法，该方法所需纯化步骤最少，顺式：反式非对映选择性良好（约为1:4），且产率较高。开展了在异恶唑啉环存在下用二水合二氯化锡还原芳基硝基的表面结合研究，以确认异恶唑啉环的稳定性。在样品库合成过程中，对这种基于螺异恶唑啉脯氨酸的氨基酸支架进行了完全衍生化，产率高且纯度高，验证了用于树脂结合库合成的化学方法的效率。利用双氨基酸编码方法和TentaGel树脂的双功能化，合成了一个基于支架7的129,600成员的单珠单化合物（OBOC）库。