Department of Chemistry, Stanford University, Stanford, California 94305-5080, United States.
J Am Chem Soc. 2010 Nov 24;132(46):16403-16. doi: 10.1021/ja105129p. Epub 2010 Nov 2.
Asymmetric total synthesis of bryostatin 16 was achieved in 26 steps in the longest linear sequence and in 39 total steps from aldehyde 10. A Pd-catalyzed alkyne-alkyne coupling was employed for the first time as a macrocyclization method in a natural product synthesis. A route to convert bryostatin 16 to a new family of bryostatin analogues was developed. Toward this end, 20-epi-bryostatin 7 was synthesized from a bryostatin 16-like intermediate; the key step involves a Re-catalyzed epoxidation/ring-opening reaction. Preliminary biological studies indicated that this new analogue exhibits nanomolar anti-cancer activity against several cancer cell lines.
16-去甲软海绵素 B 的不对称全合成以最长线性序列 26 步和总 39 步从醛 10 实现。首次将钯催化的炔-炔偶联用于天然产物合成中的大环化方法。开发了将 16-去甲软海绵素 B 转化为新型软海绵素类似物的途径。为此，从 16-去甲软海绵素 B 样中间体合成了 20-表-软海绵素 7；关键步骤涉及 Re 催化的环氧化/开环反应。初步的生物学研究表明，这种新类似物对几种癌细胞系具有纳摩尔级的抗癌活性。
