Total Synthesis of Nocarterphenyl A, 2‑Dehydroxymethylnocarterphenyl A and Nocarterphenyl D Produced by Marine Nocardiopsis spp.

We report the divergent total synthesis of marine natural products nocarterphenyl A (1), 2-dehydroxymethylnocarterphenyl A (2), and nocarterphenyl D (3). The thiazole-fused p-terphenyl core was synthesized via Suzuki–Miyaura coupling, and dibrominated precursor 6 was obtained by dibromination of a multisubstituted benzothiazole 7 using NBS/morpholine/HFIP. Nocarterphenyl D (3) was synthesized through palladium-catalyzed dehydrogenation cross-coupling. Biological evaluation revealed that nocarterphenyl A (1) inhibited HCT116 cell proliferation by 71% at 10 μM. Preliminary structure–activity relationships are discussed.

本研究报道了海洋天然产物诺卡苯菲A（nocarterphenyl A，1）、2-去羟甲基诺卡苯菲A（2-dehydroxymethylnocarterphenyl A，2）以及诺卡苯菲D（nocarterphenyl D，3）的发散式全合成。噻唑稠合对三联苯母核通过铃木-宫浦（Suzuki–Miyaura）偶联反应合成；以N-溴代琥珀酰亚胺/吗啉/六氟异丙醇（NBS/morpholine/HFIP）体系对多取代苯并噻唑7进行二溴化反应，得到二溴代前体6。诺卡苯菲D（3）则通过钯催化脱氢交叉偶联反应完成合成。生物学活性评价结果显示，在10 μM浓度下，诺卡苯菲A（1）对HCT116细胞增殖的抑制率可达71%。本研究还对初步构效关系进行了讨论。