Short-step synthesis and structure-activity relationship of cortistatin A analogs

被引：4

作者：

Kotoku, Naoyuki ^{[1
]}

Ito, Aoi ^{[1
]}

Shibuya, Shunichi ^{[1
]}

Mizuno, Kanako ^{[1
]}

Takeshima, Aki ^{[1
]}

Nogata, Masaki ^{[1
]}

Kobayashi, Motomasa ^{[1
]}

机构：

[1] Osaka Univ, Grad Sch Pharmaceut Sci, 1-6 Yamada Oka, Suita, Osaka 5650871, Japan

来源：

TETRAHEDRON | 2017年 / 73卷 / 10期

基金：

日本科学技术振兴机构;

关键词：

Cortistatin A; Anti-angiogenesis; Marine sponge; Analog synthesis; Structure-activity relationship; SPONGE CORTICIUM-SIMPLEX; STEROIDAL ALKALOIDS; NATURAL-PRODUCTS; BIOLOGICAL EVALUATION; CHEMISTRY; DISCOVERY; SYNTHON; POTENT;

D O I：

10.1016/j.tet.2017.01.042

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

An improved method for synthesizing structurally simplified analogs of cortistatin A (1), a novel antiangiogenic steroidal alkaloid from a marine sponge, was developed. In contrast to previous methods, step-and redox-economical synthesis was achieved using a known alpha-bromoketone as the starting material. The structure-activity relationship study revealed that the isoquinoline portion was strictly recognized by the target molecule. Surprisingly, the introduction of the acetamide moiety on the A-ring structure dramatically enhanced the selective antiproliferative activity against endothelial cells. This new method can be easily applied to gram-scale synthesis and enabled us to prepare various analogs, which were focused on the participation of the side chain and A-ring structure. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：1342 / 1349

页数：8