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Tricyclic CNS Active Agents by Intramolecular Oxa ‐ Pictet ‐ Spengler Reaction
Author(s) -
Wünsch Bernhard,
Zott Matthias,
Höfner Georg,
Bauschke Gerd
Publication year - 1995
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19953280604
Subject(s) - chemistry , stereochemistry , intramolecular force , moiety , enantiomer , tricyclic , acetal , phencyclidine , mitsunobu reaction , nmda receptor , receptor , biochemistry
Mitsunobu inversion of the ( S )‐configurated lactate ( S )‐ 7 , which is prepared in four steps starting form ( S )‐tyrosine, leads to the ( R )‐configurated lactate ( R )‐ 7 . The key step in the transformation of the enantiomeric lactates ( S )‐ 7 and ( R )‐ 7 into the benzomorphan analogous tricycles ( R , S )‐ 16a,b , ( S , R )‐ 16a,b , ( S , S )‐ 22 , and ( R , R )‐ 22 is an intramolecular Oxa ‐ Pictet ‐ Spengler reaction: The amides ( S )‐ 13 , ( R )‐ 13 , ( S )‐ 19 and ( R )‐ 19 , in which the carbonyl moiety — masked as an acetal — is linked to the 2‐phenylethanol moiety, are cyclized to give the tricyclic amides ( R , S )‐ 15 , ( S , R )‐ 15 , ( S , S )‐ 21 , and ( R , R )‐ 21 , respectively. In a concentration of 100 μM both enantiomers of 16a, 16b , and 22 are not able to compete with 3 H‐(+)‐MK 801 for the phencyclidine binding sites of NMDA receptors. In vivo , only ( R , S )‐ 16b and ( S , S )‐ 22 exhibit weak sedative and analgesic activity.