Synthesis and Structural Analysis of Angular Monoprotected Diamines Based on Spiro[3.3]heptane Scaffold
Synthesis and Structural Analysis of Angular Monoprotected Diamines Based on Spiro[3.3]heptane Scaffold
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DOI：
10.1021/acs.joc.5b00323
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发表时间：
2015-04-17
影响因子：
3.6
通讯作者：
Komarov, Igor V.
中科院分区：
文献类型：
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作者：
Chernykh, Anton V.;Radchenko, Dmytro S.;Komarov, Igor V.
报道了螺[3.3]庚烷-1，6-二胺的所有立体异构体的合成，所述螺[3.3]庚烷-1，6-二胺被适当地保护以用作药物发现中的结构单元。结构分析揭示了螺[3.3]庚烷和环己烷支架之间的相似性。通过比较官能团间的距离和空间取向，证明了（1 S，4 r，6 R）-和（1 R，4 r，6S）-1，6-二取代螺[3.3]庚烷可以作为顺式-1，4-二取代环己烷衍生物的限制性替代物。类似地，（1 S，4s，6 R）-和（1 R，4s，6S）-1，6-二取代螺[3.3]庚烷是反式-1，3-二取代环己烷的受限替代物。这种替代可以推荐用于药物发现中先导化合物的ADME参数的优化。
The synthesis of all stereoisomers of spiro[3.3]heptane-1,6-diamines suitably protected for use as building blocks in drug discovery is reported. Structural analysis revealed the similarity between the spiro[3.3]heptane and cyclohexane scaffolds. Comparison of the distance between functional groups and their spatial orientation proved that (1S,4r,6R)- and (1R,4r,6S)-1,6-disubstituted spiro[3.3]heptanes can be considered as restricted surrogates of cis-1,4-disubstituted cyclohexane derivatives. Similarly, (1S,4s,6R)- and (1R,4s,6S)-1,6-disubstituted spiro[3.3]heptanes are the restricted surrogates of trans-1,3-disubstituted cyclohexanes. Such replacement can be recommended for use in optimization of ADME parameters of lead compounds in drug discovery.