Tricycles by a new Ugi variation and Pictet-Spengler reaction in one pot.
Tricycles by a new Ugi variation and Pictet-Spengler reaction in one pot.
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DOI：
10.1002/chem.201300962
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发表时间：
2013-06-17
影响因子：
4.3
通讯作者：
Doemling, Alexander
中科院分区：
文献类型：
--
作者：
Sinha, Mantosh K.;Khoury, Kareem;Herdtweck, Eberhardt;Doemling, Alexander
支架的化学多样性和复杂性是基于设计或筛选的有用材料发现的关键。基于特定支架的一系列化合物通常用于优化性能。尽管支架传统上是通过顺序多步合成构建的，但收敛的替代途径涉及一锅多组分反应 (MCR)。 [1]我们最近在 MCR 背景下引入了支架的有用定义，因此它被定义为“通过使用具有共同官能团的起始材料进行反应或反应序列而产生的最小原子分母及其连接性。”[2]过去基于不同的策略描述了各种各样的 MCR 支架。[3]例如，MCR 可访问超过 40 个哌嗪支架。[2]两步 Ugi MCR/成环 Pictet-Spengler 反应特别令人感兴趣，因为它可以得到相当刚性、复杂的多环产物，这可以导致熵优先的受体结合（方案 1）。该反应序列已用于药物和天然产物的合成以及化学生物学工具。我们描述了通过 Ugi-Pictet-Spengler 序列对血吸虫病药物吡喹酮 1 进行最短的可规模合成。 [4]相同的路线可用于合成生物活性吡喹酮衍生物，否则不可行。 [5] Almorexant 2 是一种选择性口服生物可利用的食欲素 I 拮抗剂，最近开始 III 期临床试验，并通过一系列 Ugi-Pictet-Spengler 反应发现。 [6]通过使用双官能团氧代羧酸，可以方便地合成诸如 3 等具有更多稠环的化合物。 [7]蒂亚吉等人。在 Groebcke-Blackburn-Bienaymé 变体中进行 Ugi 反应，然后进行 Pictet-Spengler 反应，得到稠环系统的几个不同骨架，例如 4.[8]苯乙胺衍生的异氰化物只需两步即可转化为具有前所未有的复杂性的多环产物 (5)。 [9]莱斯玛等人。
Chemical diversity and complexity of scaffolds are key for the design-or screening-based discovery of useful materials. Series of compounds based on a particular scaffold are often used to optimize properties. Although scaffolds are traditionally built up by sequential multistep syntheses, a convergent alternative pathway involves one-pot multicomponent reactions (MCRs).[1] A useful definition of the scaffold in the context of MCR has been introduced recently by us, and accordingly it is defined “as the smallest atomic denominator and its connectivity as resulting from a reaction or reaction sequence by using starting materials with common functional groups.”[2] A very large variety of MCR scaffolds have been described in the past based on different strategies.[3] For example, there are more than 40 piperazine scaffolds accessible by MCR.[2] The two-step Ugi MCRs/ring-forming Pictet–Spengler reaction is of particular interest, because it gives access to rather rigid, complex polycyclic products, which can lead to entropically preferred receptor binding (Scheme 1). This reaction sequence has been used for the synthesis of drugs and natural products, as well as for chemical-biology tools.We described the shortest scalable synthesis of the schistosomiasis drug praziquantel 1 by an Ugi–Pictet–Spengler sequence.[4] The same route can be used for the synthesis of bioactive Praziquantel derivatives otherwise not amenable.[5] Almorexant 2, a selective and orally bioavailable orexin I antagonist recently began phase III clinical trials and was discovered by a sequence Ugi–Pictet–Spengler reactions.[6] By using a bifunctional oxocarboxylic acid, compounds, such as 3 with even more condensed cycles, can be conveniently synthesized.[7] Tyagi et al. performed the Ugi reaction in the Groebcke–Blackburn–Bienaymé variation followed by a Pictet–Spengler reaction to give several distinct skeletons of fused ring systems, for example, 4.[8] Phenylethylamine-derived isocyanides can be converted in just two steps to polycyclic products with unprecedented complexity (5).[9] Lesma et al.
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影响因子：
3.2
作者：
Lesma, Giordano;Cecchi, Roberto;Silvani, Alessandra
通讯作者：
Silvani, Alessandra
影响因子：
3.6
作者：
Tyagi, Vikas;Khan, Shahnawaz;Chauhan, Prem M. S.
通讯作者：
Chauhan, Prem M. S.
影响因子：
5.2
作者：
Mori, K;Rikimaru, K;Fukuyama, T
通讯作者：
Fukuyama, T
影响因子：
3
作者：
Liu H;William S;Herdtweck E;Botros S;Dömling A
通讯作者：
Dömling A
影响因子：
0.6
作者：
UGI, I;DOMLING, A;HORL, W
通讯作者：
HORL, W