Concise total synthesis of sintokamides A, B, and E by a unified, protecting-group-free strategy.
Concise total synthesis of sintokamides A, B, and E by a unified, protecting-group-free strategy.
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DOI：
10.1002/anie.201005354
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发表时间：
2010-12-10
影响因子：
16.6
通讯作者：
Zakarian, Armen
中科院分区：
文献类型：
--
作者：
Gu, Zhenhua;Zakarian, Armen
到目前为止，已分离和鉴定了4000多种卤代天然产物。[1]这些化合物具有广泛的生物活性，包括抗肿瘤、抗HIV、[3]和镇痛活性。[4]含有二氯甲基或三氯甲基的氯化海洋天然产物，如巴巴胺、[5]双噻唑胺、[6]和地塞米德，[7]是一类重要的化合物。2006年，Gerwick和Walsh小组发现了一类新的卤化酶，它能在与多肽载体蛋白相连的氨基酸残基的未活化脂肪碳原子上催化卤代反应。[8]然而，立体选择性二或三氯甲基化的化学方法仍然有限。[9]最近，我们的研究小组描述了一种实用而有效的方法，用于高非对映选择性的钛烯醇酸盐的卤代烷化反应。[10]Sadar等人分离了蓝藻代谢物sintokamines A-E。从海绵Dyidea sp.在寻找治疗激素难治性前列腺癌的天然产物衍生药物(方案1)期间，在印度尼西亚帕劳辛托克附近采集。[11]通过X射线衍射分析建立了辛托卡胺A的相对和绝对构型。辛托卡胺是第一个被报道选择性地阻断前列腺癌细胞雄激素受体N末端反式激活的天然产品。此外，研究发现辛托卡胺A与比卡鲁胺一样有效地阻断了雄激素诱导的雄激素敏感的LNCaP前列腺癌细胞的增殖。
Considered rare and exotic only about 50 years ago, more than 4000 halogenated natural products have been isolated and characterized to date.[1] These compounds exhibit a wide range of biological activity, including antitumor,[2] anti-HIV,[3] and analgesic activity.[4] Chlorinated marine natural products containing dichloromethyl or trichloromethyl groups, such as barbamide,[5] dysithiazolamide,[6] and dysamide,[7] constitute an important subclass of compounds. In 2006, the Gerwick and Walsh groups uncovered a novel class of halogenating enzymes that catalyzed halogenation at unactivated aliphatic carbon atoms of amino acid residues linked to a peptide carrier protein.[8] However, chemical methods for stereoselective di-or trichloromethylation are still limited.[9] Recently, our research group described a practical and efficient method for the haloalkylation of titanium enolates with high diastereoselectivity.[10]The cyanobacterial metabolites sintokamides A–E were isolated by Sadar et al. from the marine sponge Dysidea sp. collected near Palau Sintok, Indonesia, during the search for natural product derived drugs for the treatment of hormone-refractory prostate cancer (Scheme 1).[11] The relative and absolute configuration of sintokamide A was established by X-ray diffraction analysis. The sintokamides are the first natural products reported to selectively block transactivation of the N terminus of the androgen receptor in prostate cancer cells. Furthermore, it was found that sintokamide A is as effective as bicalutamide in blocking androgen-induced proliferation in androgen-sensitive LNCaP prostate cancer cells.[11]
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影响因子：
64.8
作者：
Baran, Phil S.;Maimone, Thomas J.;Richter, Jeremy M.
通讯作者：
Richter, Jeremy M.
DOI：
10.1039/p19870001177
发表时间：
1987-06-01
期刊：
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1
影响因子：
--
作者：
JOUIN, P;CASTRO, B;NISATO, D
通讯作者：
NISATO, D
影响因子：
2
作者：
Jeong, Yong-Chul;Moloney, Mark G.
通讯作者：
Moloney, Mark G.
影响因子：
1.8
作者：
BAJWA, JS;ANDERSON, RC
通讯作者：
ANDERSON, RC
DOI：
10.1073/pnas.0506964102
发表时间：
2005-09-27
影响因子：
11.1
作者：
Dorrestein, PC;Yeh, E;Walsh, CT
通讯作者：
Walsh, CT