Pandya Bhaumik A, Dandapani Sivaraman, Duvall Jeremy R, Rowley Ann, Mulrooney Carol A, Ryba Troy, Dombrowski Michael, Harton Marie, Young Damian W, Marcaurelle Lisa A
Chemical Biology Platform, The Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA.
Tetrahedron. 2011 Aug 26;67(34):6131-6137. doi: 10.1016/j.tet.2011.06.043.
Orthogonally protected chiral β-hydroxy-γ-amino acids can be accessed in >100 g quantities from readily available starting materials and reagents in 3-4 steps. These chiral synthons contain two adjacent stereocenters along with suitably protected functional groups (O-TBS, N-Boc) for downstream reactivity. Implementation of two existing aldol technologies allows rapid access to all possible stereoisomers of 1. The guiding principles during reaction optimization were reaction scalability and operational efficiency. Conversion of the amino acids to a variety of chiral building blocks in 1-2 steps demonstrates their synthetic utility.
通过3至4步反应，可从容易获得的起始原料和试剂中大量制备（超过100克）正交保护的手性β-羟基-γ-氨基酸。这些手性合成子包含两个相邻的立体中心以及用于下游反应性的适当保护的官能团（O-TBS、N-Boc）。采用两种现有的羟醛缩合技术能够快速获得化合物1的所有可能立体异构体。反应优化过程中的指导原则是反应的可扩展性和操作效率。这些氨基酸在1至2步反应中转化为各种手性结构单元，证明了它们的合成效用。
