Linked Life Data

16268624

Source:http://linkedlifedata.com/resource/pubmed/id/16268624

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2005-11-4
pubmed:abstractText
[Reaction: see text]. The enantioselective synthesis of both enantiomers of tetrahydropalmatine (2) (ee = 98%), a natural alkaloid belonging to the tetrahydroprotoberberine family, is described. The key step of this total synthesis is based on our tandem 1,2-addition/ring-closure methodology employing lithiated methylbenzamide and benzaldehyde SAMP or RAMP hydrazones as substrates. An initial route was investigated for the formation of N- and 3-substituted dihydroisoquinolones starting from 2-substituted benzaldehyde SAMP hydrazones, but although high diastereoselectivity was achieved, only disappointing yields were obtained. In our subsequent synthetic strategy, 2,3-dimethoxy-6-methylbenzamide 6 and 3,4-dimethoxybenzaldehyde SAMP or RAMP hydrazone 19 gave the dihydroisoquinolones 20 in high diastereomeric purity (de > or = 96%) and reasonable yield (54-55%), taking into account the complex functionalities established in one step. Cleavage of the N-N bond of the chiral auxiliary and reduction of the carbonyl group of the amide moiety were performed in the same step, and the resulting tetrahydroisoquinolines 22 (ee = 99%) were N-functionalized by treatment with various electrophiles to investigate the ring closure by Pummerer, Friedel-Crafts, and Pomeranz-Fritsch reactions. The Pummerer cyclization led to the formation of (S)-(-)-2 with slight racemization (ee = 89%), whereas the Friedel-Crafts reaction proved to be unsuccessful. Finally, Pomeranz-Fritsch-type cyclization afforded the desired title compound (R)-(+)-2 in excellent enantioselectivity in 9% overall yield over seven steps and after optimization of the last step (S)-(-)-2 in 17% overall yield.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-3263
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
70
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9486-94
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Asymmetric synthesis of tetrahydropalmatine via tandem 1,2-addition/cyclization.
pubmed:affiliation
Institut für Organische Chemie, RWTH Aachen, Landoltweg 1, D-52074 Aachen, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't