ChemInform Abstract: Preparation and Diastereoselective Birch Reduction—Alkylation of Chiral 3,4-Dihydro-1(2H)-isoquinolinones. Enantiospecific Syntheses and Opioid Receptor Affinities of Several Hydro-2,3-dimethyl-1H-7,12a-methanobenzo[6,7]cycloocta [1,2-c]pyridine-9-ols.
✍ Scribed by Arthur G. Schultz; Timothy J. Guzi; Erika Larsson; Rainer Rahm; Kshitij Thakkar; Jean M. Bidlack
- Publisher
- John Wiley and Sons
- Year
- 2010
- Weight
- 40 KB
- Volume
- 30
- Category
- Article
- ISSN
- 0931-7597
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✦ Synopsis
Preparation and Diastereoselective Birch Reduction-Alkylation of Chiral 3,4-Dihydro-1(2H)-isoquinolinones. Enantiospecific Syntheses and Opioid Receptor Affinities of Several 7]cycloocta [1,2-c]pyridine-9-ols.
-Treatment of isoquinolines, readily prepared from natural precursors such as ephedrine (I) and phenylalanine (VII), under Birch reduction conditions followed by alkylation with alkyl halides affords the corresponding products with high diastereoselectivities (90-94% d.e.). The stereocontrol is comparable to that found for alkylations of anions generated from bislactam ethers. The benzyl-substituted isoquinolines undergo Grewe cyclizations to yield cyclohexene derivatives which are converted to enantiomerically pure tetracycles like (VI). These new compounds are tested for their opioid receptor affinities; none of them is found to be highly efficient. Both cis-and trans-isoquinolone ring systems (XI) and (XII) are available by simple iodoetherification reactions under either kinetic or thermodynamic control. -(SCHULTZ, ARTHUR G.;