Department of Chemistry and Biochemistry, Baylor University, 101 Bagby Avenue, Waco, Texas 76798-7046, United States.
Org Lett. 2020 Dec 4;22(23):9282-9286. doi: 10.1021/acs.orglett.0c03511. Epub 2020 Nov 23.
A concise, organocatalytic, enantioselective route to the γ-lactam core of the oxazolomycins was developed. Key steps include a Lewis base-catalyzed, Michael proton transfer-lactamization organocascade, a one-pot N-methylation and diastereoselective α-alkylation, a diastereotopic group-selective reduction, a substrate-directed allylic hydroxylation, and a lanthanide-mediated organolithium addition to append the side chain. A formal synthesis of (+)-neooxazolomycin via interception of a Kende intermediate, accessed in 10 steps (previously 24 steps from α-d-glucose), enabled confirmation of the relative and absolute stereochemistry.
开发了一种简洁、有机催化、对映选择性的途径，用于合成氧杂霉素的γ-内酰胺核心。关键步骤包括路易斯碱催化的迈克尔质子转移-内酰胺化有机级联反应、一锅 N-甲基化和非对映选择性α-烷基化、非对映选择性基团选择性还原、底物导向的烯丙基羟化和镧系元素介导的添加侧链的有机锂加成。通过捕获 Kende 中间体（之前从α-D-葡萄糖中需要 24 步）进行（+）-新氧杂霉素的形式合成，验证了相对和绝对立体化学。
