Process development on an efficient new convergent formal synthesis of MIV-150
Process development on an efficient new convergent formal synthesis of MIV-150
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DOI：
10.1021/op0341871
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发表时间：
2004-05-01
影响因子：
3.4
通讯作者：
Therrien, J
中科院分区：
文献类型：
--
作者：
Cai, SP;Dimitroff, M;Therrien, J
从一条已知的线性路线和一条建议的收敛路线出发，我们成功地开发了一条新的杂化聚合路线，该路线利用了制备氟缩酮和碘环丙烷部分与苯环的立体特异性Negishi偶联的强大化学优势。发展了立体选择性的β-和顺式碘化化学，用于制备对映体纯的碘代环丙烷羧酸盐。在Negishi偶联之后，加入了来自线性路线的经过验证的化学物质，从而确保了最终活性药物成分(API)具有类似的高纯度特征。此外，我们还制备并评价了一系列碱性无机和有机MIV-150盐，这些盐与母体化合物相比，大大增加了水的溶解度。
Starting from a known linear route and a proposed convergent route, we have successfully developed a new hybrid convergent route to MIV-150 that takes advantage of the robust chemistry for the preparation of a fluoroketal and the stereospecific Negishi coupling of an iodocyclopropane moiety to a benzene ring. Stereoselective beta- and cis-iodination chemistry was developed for the preparation of an enantiomerically pure iodocyclopropanecarboxylate. Following the Negishi coupling, proven chemistry from the linear route was incorporated, thus ensuring a similar high-purity profile for the final active pharmaceutical ingredient (API). In addition, we have prepared and evaluated a series of basic inorganic and organic MIV-150 salts that have drastically increased water solubility over the parent compound.