DeMattei J A, Leanna M R, Li W, Nichols P J, Rasmussen M W, Morton H E
Process Research, Pharmaceutical Products Division, Abbott Laboratories, North Chicago, Illinois 60064-4000, USA.
J Org Chem. 2001 May 18;66(10):3330-7. doi: 10.1021/jo0057203.
ABT-271, 1, has been identified as a promising anticancer agent. ABT-271 is a novel taxane possessing a C9-(R)-hydroxyl group as opposed to a C9-ketone which is present in Taxol and Taxotere. To further evaluate ABT-271 as a potential anticancer agent, an efficient synthesis was developed which allows the large scale synthesis of ABT-271. Ketalization of the 7,9-diol of 9-DHAB-III, 2, allows selective removal of the C13-acetate with phenyllithium. The resulting C13-hydroxyl group is then acylated using LiHMDS and beta-lactam 22 to give ABT-271 in protected form. The protecting groups were removed first by acidic hydrolysis followed by basic hydrolysis to provide ABT-271. Application of this synthetic sequence provided over 600 g of ABT-271, 1.
ABT-271（1）已被确认为一种有前景的抗癌药物。ABT-271是一种新型紫杉烷，具有C9-(R)-羟基，与紫杉醇和多西他赛中存在的C9-酮不同。为了进一步评估ABT-271作为潜在抗癌药物的效果，开发了一种高效合成方法，可实现ABT-271的大规模合成。9-DHAB-III（2）的7,9-二醇进行缩酮化反应，能使苯基锂选择性地去除C13-乙酸酯。然后使用LiHMDS和β-内酰胺22对生成的C13-羟基进行酰化，得到保护形式的ABT-271。首先通过酸性水解去除保护基团，然后进行碱性水解，得到ABT-271。应用此合成序列得到了超过600克的ABT-271（1）。
