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Enantioselective, Protecting‐Group‐Free Total Synthesis of Sarpagine Alkaloids—A Generalized Approach
Author(s) -
Krüger Sebastian,
Gaich Tanja
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201407280
Subject(s) - enantioselective synthesis , total synthesis , protecting group , indole test , stereochemistry , sequence (biology) , cycloaddition , ring (chemistry) , chemistry , combinatorial chemistry , group (periodic table) , organic chemistry , catalysis , biochemistry , alkyl
A generalized synthetic access to sarpagine alkaloids through a joint synthetic sequence has been accomplished. Its applicability is showcased by the enantioselective total syntheses of vellosimine ( 1 ), N ‐methylvellosimine ( 3 ), and 10‐methoxyvellosimine ( 8 ). The synthetic sequence is concise (eight steps) from known compound 13 , and requires no protecting groups. The indole heterocycle was introduced in the last step. This strategy allows access to sarpagine alkaloids through a shared synthetic route leading to precursor 10 , which we term “privileged intermediate”. Starting from this intermediate, all sarpagine alkaloids can be synthesized using phenylhydrazines with different substitution patterns ( 15 – 17 ). Our approach brings about the advantage, that synthesis optimization only needs to be performed once for many natural products. The key features of the synthesis are a [5+2]‐cycloaddition and a ring enlargement.