Synthetic Studies toward Ecteinascidin 743

An 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)]


Published in:
Journal of Organic Chemistry, 70, 11, 4397-4408
Year:
2005
Keywords:
Note:
CAN 143:60125
31-6
Alkaloids
Institut de Chimie des Substances Naturelles,CNRS,Gif-sur-Yvette,Fr.
Journal
0022-3263
written in English.
654644-01-6P Role: PRP (Properties), SPN (Synthetic preparation), PREP (Preparation) (crystal structure; synthetic studies toward ecteinascidin 743); 200132-54-3 Role: CAT (Catalyst use), USES (Uses) (synthetic studies toward ecteinascidin 743); 108-88-3 (Toluene); 920-66-1 Role: NUU (Other use, unclassified), USES (Uses) (synthetic studies toward ecteinascidin 743); 114899-77-3P (Ecteinascidin 743) Role: PNU (Preparation, unclassified), PREP (Preparation) (synthetic studies toward ecteinascidin 743); 106-95-6 (Allyl bromide); 488-17-5; 533-31-3 (1,3-Benzodioxol-5-ol); 924-44-7 (Ethyl glyoxylate); 2799-07-7; 3966-32-3; 26164-26-1; 81477-94-3; 95715-87-0; 96845-11-3 Role: RCT (Reactant), RACT (Reactant or reagent) (synthetic studies toward ecteinascidin 743); 111726-43-3P; 187040-02-4P; 187040-03-5P; 654643-96-6P; 654643-97-7P; 654643-98-8P; 654643-99-9P; 654644-00-5P; 654644-02-7P; 654644-03-8P; 654644-04-9P; 686776-20-5P; 686776-21-6P; 686776-22-7P; 686776-23-8P; 686776-24-9P; 686776-25-0P; 686776-28-3P; 686776-29-4P; 854021-71-9P; 854021-83-3P; 854021-99-1P; 854022-02-9P; 854022-04-1P; 854022-09-6P; 854022-14-3P; 854022-23-4P; 854022-25-6P; 854022-31-4P; 854022-33-6P; 854022-35-8P; 854022-39-2P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (synthetic studies toward ecteinascidin 743); 7447-41-8 (Lithium chloride) Role: RGT (Reagent), RACT (Reactant or reagent) (synthetic studies toward ecteinascidin 743); 654643-95-5P; 854021-95-7P; 854021-97-9P; 854022-01-8P; 854022-06-3P; 854022-12-1P; 854022-29-0P; 854022-37-0P Role: SPN (Synthetic preparation), PREP (Preparation) (synthetic studies toward ecteinascidin 743)
Laboratories:




 Record created 2010-11-25, last modified 2018-03-17


Rate this document:

Rate this document:
1
2
3
 
(Not yet reviewed)