Chen, XiaochuanChen, JinchunDe Paolis, MichaelZhu, Jieping2010-11-252010-11-252010-11-25200510.1021/jo050408khttps://infoscience.epfl.ch/handle/20.500.14299/58473An efficient synthesis of a fully functionalized tetracyclic fragment (A-B-C-H) I of ecteinascidin 743, contg. a 1,4-bridged 10-membered lactone, is reported. The synthesis is highly convergent and has been carried out on a multigram scale featuring the following key steps: union of two fragments II and III via an oxazolidine intermediate; and acid-promoted macrocyclization via formation of a carbon-sulfur bond with concomitant formation of the 10-membered ring. Although compd. I was responsive to the intramol. Pictet-Spengler reaction, a destructive ring opening of the 1,4-bridged lactone also occurred, leading to the formation of pentacyclic compd. IV. In the course of this study, it was discovered that a combination of a mild Lewis acid and a mild Bronsted acid constituted excellent reagents for performing the Pictet-Spengler reaction of a highly acid-sensitive substrate. [on SciFinder (R)]Cyclocondensation reaction (Pictet-Spengler; synthetic studies toward ecteinascidin 743); Amination (Strecker; synthetic studies toward ecteinascidin 743); Macrocyclization (acid-promoted macrocyclization; synthetic studies toward ecteinascidin 743); Crystal structure; Molecular structure (of a substituted phenolic intermediate in synthetic studies toward ecteinascidin 743); Asymmetric synthesis and induction; Condensation reaction (synthetic studies toward ecteinascidin 743)asym synthesis ecteinascidin 743 tetracycle condensation Strecker Pictet Spengler; crystal mol structure phenolic intermediatetext::journal::journal article::research article