A decagram-scale synthesis of seven new building blocks of 1-oxaspiro[3.3]heptane family is described. This general approach requires 6 to 13 operationally simple steps starting from commercially available and inexpensive 3-oxocyclobutane-1-carboxylic acid. Expedient synthetic routes enable the straightforward access to these novel modules. Finally, the generation of virtual combinatorial library using the LLAMA software showed that building blocks described here demonstrated the high propensity to populate the lead-like chemical space. Like pigeons delivering letters, the newly 1-oxaspiro[3.3]heptane family scaffolds could deliver their functionality to drug-like compounds that are expected to be important in drug discovery and design.

描述了 1-oxaspiro[3.3] 庚烷家族的七个新构建块的十克级合成。这种通用方法需要 6 到 13 个简单的操作步骤，从市售且廉价的 3-oxocyclobutane-1-carboxylic acid 开始。方便的合成路线可以直接访问这些新模块。最后，使用 LLAMA 软件生成的虚拟组合库表明，此处描述的构建基块展示了填充类铅化学空间的高倾向性。就像传递信件的鸽子一样，新的 1-oxaspiro[3.3] 庚烷家族支架可以将其功能传递给预计在药物发现和设计中具有重要意义的类药化合物。