Department of Chemistry, Pondicherry University, Puducherry 605014, India.
Department of Chemistry, National Dong Hwa University, Shoufeng Township, Hualien County 974, Taiwan.
Molecules. 2020 Feb 14;25(4):831. doi: 10.3390/molecules25040831.
The total synthesis of (-)-antrocin and its enantiomer are presented. Antrocin (-)- is an important natural product which acts as an antiproliferative agent in a metastatic breast cancer cell line (IC: 0.6 M). The key features of this synthesis are: (a) selective anti-addition of trimethylsilyl cyanide (TMSCN) to -unsaturated ketone; (b) resolution of (±) using chiral auxiliary L-dimethyl tartrate through formation of cyclic ketal diastereomers followed by simple column chromatography separation and acid hydrolysis; (c) substrate-controlled stereoselective aldol condensation of (+)- with monomeric formaldehyde and pyridinium chlorochromate (PCC) oxidation for synthesis of essential lactone core in (-)-; and (d) non-basic Lombardo olefination of the carbonyl at the final step to yield (-)-antrocin. In addition, (+) cyclic ketal diastereomer was converted to (+)-antrocin with similar reaction sequences.
本文报道了（-）-安托辛及其对映体的全合成。（-）-安托辛是一种重要的天然产物，在转移性乳腺癌细胞系中具有抗增殖作用（IC：0.6 M）。该合成的关键特点是：（a）三甲基硅氰化物（TMSCN）对-不饱和酮的选择性反加成；（b）通过形成环状酮缩醛非对映异构体，使用手性助剂 L-酒石酸二甲酯拆分（±），然后通过简单的柱层析分离和酸水解；（c）（+）-与单体甲醛和吡啶氯铬酸盐（PCC）的底物控制立体选择性羟醛缩合，用于（-）-中必需内酯核心的合成；以及（d）在最后一步进行非碱性隆巴尔多烯烃化，以得到（-）-安托辛。此外，（+）-环状酮缩醛非对映异构体也通过类似的反应序列转化为（+）-安托辛。
