Liang Ningning, Datta Apurba
Department of Medicinal Chemistry, The University of Kansas, 1251 Wescoe Hall Drive, Lawrence, Kansas 66045, USA.
J Org Chem. 2005 Nov 25;70(24):10182-5. doi: 10.1021/jo051725u.
[reaction: see text] 3-Hydroxypipecolic acid, a nonproteinogenic cyclic alpha-amino acid, is a common structural moiety found in a large number of natural and synthetic compounds of medicinal significance. Utilizing D-serine as a chiral template, the present research describes efficient and straightforward routes to cis- and trans-3-hydroxypipecolic acids in enantiopure form. The key steps in the syntheses involve chelation-controlled addition of a homoallyl Grignard reagent to a protected serinal derivative toward stereoselective formation of the corresponding syn-amino alcohol adduct 3. On the other hand, zinc borohydride-mediated chelation-controlled reduction of a serine-derived alpha-aminoketone precursor leads to the formation of the corresponding anti-amino alcohol adduct 4 with high stereoselectivity. Following an efficient sequence of reactions, the above amino alcohol derivatives were subsequently transformed to the corresponding cis- and trans- title compounds, respectively.
[反应：见正文] 3-羟基哌啶酸是一种非蛋白质ogenic环状α-氨基酸，是在大量具有药用意义的天然和合成化合物中发现的常见结构部分。本研究以D-丝氨酸为手性模板，描述了对映体纯形式的顺式和反式3-羟基哌啶酸的高效直接合成路线。合成中的关键步骤包括将高烯丙基格氏试剂螯合控制加成到受保护的丝氨醇衍生物上，以立体选择性地形成相应的顺式氨基醇加合物3。另一方面，硼氢化锌介导的丝氨酸衍生的α-氨基酮前体的螯合控制还原导致以高立体选择性形成相应的反式氨基醇加合物4。按照有效的反应顺序，上述氨基醇衍生物随后分别转化为相应的顺式和反式标题化合物。
