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Synthesis of the Preininger ‐Alkaloid and its Enantioselective Reduction to Macrostomine
Author(s) -
Mahboobi Siavosh,
Wiegrebe Wolfgang
Publication year - 1991
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.19913240504
Subject(s) - formylation , isoquinoline , chemistry , alkaloid , enantioselective synthesis , enantiomer , nitrile , reagent , stereochemistry , combinatorial chemistry , organic chemistry , catalysis
The Preininger ‐alkaloid, dehydro‐normacrostomine ( 2b , Scheme 1) was synthesized starting from rac. α‐acetyl‐3,4‐dimethoxybenzylcyanide (3) (Scheme 2). The key intermediate 4‐acetyl‐6,7‐dimethoxy‐1‐(3,4‐methylene‐dioxybenzyl)isoquinoline (11) is converted via a Mannich base to the nitrile 17 (Scheme 7) which in turn is cyclized to the Preininger ‐alkaloid (2b) by careful hydrogenation. ‐ Reduction of 2b with a modified Iwakuma ‐reagent, followed by N‐formylation and subsequent LiAlH 4 ‐reduction produced ( R )‐(+)‐macrostomine (enantiomer of 1 ) in 72% optical purity.