Organic Chemistry Laboratory, University Bayreuth, Universitaetsstrasse 30, NW 1, 95447 Bayreuth, Germany.
Chemistry. 2013 Aug 5;19(32):10619-24. doi: 10.1002/chem.201301914. Epub 2013 Jun 25.
The endofungal metabolite epicoccamide D was synthesised in eighteen steps and 17 % yield as the first member of the family of natural glycotetramic acids. The modular character of the synthesis opens access also to analogues featuring different sugars and spacers. It comprises several high-yielding key steps. The β-D-mannosyl group was introduced by using an α-D-glucosyl imidate donor with subsequent oxidative-reductive epimerisation at C-2'. The pyrrolidine ring was closed quantitatively by a Lacey-Dieckmann condensation of an N-(β-ketoacyl)-N-methyl alaninate. The resulting 3-[ω-(β-D-mannosyl)octadec-2-enoyl]tetramic acid was hydrogenated in the presence of the rhodium catalyst (R,R)-[Rh(Et-DUPHOS)][BF4 ] to establish the (7S)-stereocentre. This was possible only after blocking the acyltetramic acid as a BF2 -chelate to prevent capture of the metal catalyst. We also assigned the hitherto unknown configuration of the natural product as being 5S,7S by comparison of its (13) C NMR spectroscopic and optical rotation data with those of our two synthetic 5S,7R/S-diasteromers.
真菌代谢物 epicoccamide D 的合成历经十八步，产率为 17%，是天然甘氨四酰胺酸家族的首个成员。该合成方法具有模块化特征，还可用于具有不同糖基和间隔基的类似物。它包含多个高产率的关键步骤。β-D-甘露糖基是通过使用α-D-葡萄糖基亚氨基供体，并随后在 C-2'进行氧化还原差向异构化引入的。吡咯烷环通过 N-(β-酮酰基)-N-甲基丙氨酸的 Lacey-Dieckmann 缩合定量闭合。所得的 3-[ω-(β-D-甘露糖基)十八-2-烯酰基]四氢酸在铑催化剂 (R,R)-[Rh(Et-DUPHOS)][BF4]存在下氢化，以建立(7S)-立体中心。只有在将酰基四氢酸作为 BF2 配合物进行封闭以防止金属催化剂捕获的情况下，这才是可能的。我们还通过比较其(13)C NMR 光谱和旋光数据与我们的两种合成的 5S,7R/S-非对映异构体的数据，将天然产物的未知构型指定为 5S,7S。
