Smith Amos B, Tomioka Takashi, Risatti Christina A, Sperry Jeffrey B, Sfouggatakis Chris
Department of Chemistry, Monell Chemical Senses Center, and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Org Lett. 2008 Oct 2;10(19):4359-62. doi: 10.1021/ol801792k. Epub 2008 Aug 28.
In a quest to develop an effective, scalable synthesis of (+)-spongistatin 1 ( 1), we devised a concise, third-generation scalable synthesis of (+)- 7, the requisite F-ring tetrahydropyran aldehyde, employing a proline-catalyzed cross-aldol reaction. Subsequent elaboration to (+)-EF Wittig salt (+)- 3, followed by union with advanced ABCD aldehyde (-)- 4, macrolactonization and global deprotection permitted access to >1.0 g of totally synthetic (+)-spongistatin 1 ( 1).
为了开发一种有效、可扩展的(+)-海绵他汀1(1)合成方法,我们设计了一种简洁的第三代可扩展合成(+)-7的方法,(+)-7是所需的F环四氢吡喃醛,采用脯氨酸催化的交叉羟醛反应。随后将其转化为(+)-EF维蒂希盐(+)-3,再与高级ABCD醛(-)-4结合,进行大环内酯化和整体脱保护,从而能够获得超过1.0 g的全合成(+)-海绵他汀1(1)。