In the drug synthesis, it is usually necessary to use a group protecting agent to protect the undesired functional group to form a derivative, and then restore it to the original functional group after reaching the expected structure to improve the reaction efficiency. Hexamethyldisilazane (HMDS), as a common protective agent of silylated groups, is widely used in antibiotic synthesis and the synthesis of therapeutic drugs such as hepatitis, tumor, cardiovascular and cerebrovascular diseases. Let's introduce the application of our product hexamethyldisilazane,XY-602, in drug synthesis.
1、糖尿病治療藥物的合成
制備維格列汀中間體時,采用HMDS同時保護羥基和氨基:
2、抗生素的合成
合成頭孢烯類鎓鹽化合物時,采用HMDS同時對羧基和氨基進行硅烷化保護:
以六甲基二(er)硅(gui)氮(dan)烷作為阿米卡星合成時(shi)的反應(ying)(ying)物及溶(rong)劑,適當反應(ying)(ying)條件(jian)下,反應(ying)(ying)時(shi)間由20小時(shi)縮短至(zhi)2小時(shi),易于操作,溶(rong)劑使用量(liang)少(shao),環(huan)境(jing)友好。
3、丙肝治療藥物的合成
在制備抗丙肝病毒藥物索非布韋中間體時,先用HMDS將N-苯甲酰基胞嘧啶中的羰基轉化為硅醚,再繼續進行核苷化反應,從而實現羰基的保護:
4、抗艾滋病毒及新冠病毒藥物阿茲夫定的合成
在阿茲夫(fu)定的合成(cheng)中(zhong),以2’-氟-4’-疊氮基(ji)尿(niao)嘧(mi)啶核(he)苷中(zhong)間體(ti)為原料,采用HMDS和(he)酰胺直接將嘧(mi)啶4位羥基(ji)轉(zhuan)換成(cheng)氨基(ji),一步得(de)到胺解(jie)產物。
除(chu)了上(shang)述(shu)在基(ji)團(tuan)(tuan)保護(hu)(hu)劑方面(mian)的應用外,HMDS還可以用作催化劑以及某些惰性基(ji)團(tuan)(tuan)的活化基(ji)團(tuan)(tuan)。例如在制備廣譜抗病(bing)毒藥物利巴韋林中間體(ti)時,可先(xian)用HMDS活化1H-l,2,4-三唑-3-甲酰胺(an)的氨(an)基(ji),所得硅烷(wan)化保護(hu)(hu)氨(an)基(ji)的中間體(ti)繼續反(fan)應得到相應中間體(ti)。
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