Chi Yonggui, English Emily P, Pomerantz William C, Horne W Seth, Joyce Leo A, Alexander Lane R, Fleming William S, Hopkins Elizabeth A, Gellman Samuel H
Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
J Am Chem Soc. 2007 May 9;129(18):6050-5. doi: 10.1021/ja070063i. Epub 2007 Apr 17.
Proline-catalyzed diastereoselective aminomethylation of aldehydes using a chiral iminium ion, generated from a readily prepared precursor, provides alpha-substituted-beta-amino aldehydes with 85:15 to 90:10 dr. The alpha-substituted-beta-amino aldehydes can be reduced to beta-substituted-gamma-amino alcohols, the major diastereomer of which can be isolated via crystallization or column chromatography. The amino alcohols are efficiently transformed to protected beta2-amino acids, which are valuable building blocks for beta-peptides, natural products, and other interesting molecules. Because conditions for the aminomethylation and subsequent reactions are mild, beta2-amino acid derivatives with protected functional groups in the side chain, such as beta2-homoglutamic acid, beta2-homotyrosine, and beta2-homolysine, can be prepared in this way. The synthetic route is short, and purifications are simple; therefore, this method enables the preparation of protected beta2-amino acids in useful quantities.
脯氨酸催化醛的非对映选择性氨甲基化反应，使用由易于制备的前体生成的手性亚胺离子，可提供比例为85:15至90:10非对映体过量（dr）的α-取代-β-氨基醛。α-取代-β-氨基醛可还原为β-取代-γ-氨基醇，其主要非对映异构体可通过结晶或柱色谱法分离。氨基醇可有效转化为受保护的β2-氨基酸，它们是β-肽、天然产物及其他有趣分子的重要构建单元。由于氨甲基化及后续反应条件温和，因此可以通过这种方式制备侧链带有受保护官能团的β2-氨基酸衍生物，如β2-高谷氨酸、β2-高酪氨酸和β2-高赖氨酸。该合成路线短，纯化简单；因此，此方法能够制备出足量的受保护β2-氨基酸。
