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Synthetic Studies on Camptothecins. Part 3
Author(s) -
Kuang YunYan,
Niu JingZe,
Chen FenEr
Publication year - 2010
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.201000049
Subject(s) - chemistry , cyanohydrin , cinchona , enantioselective synthesis , bifunctional , propiophenone , thiourea , camptothecin , condensation , organic chemistry , total synthesis , cinchona alkaloids , stereochemistry , catalysis , ketone , physics , thermodynamics
A concise and efficient asymmetric process for the total synthesis of (20 S )‐7‐ethyl‐10‐hydroxycamptothecin (=SN‐38; 1f ), an active metabolic form of the prodrug irinotecan, is described. This approach features the enantioselective cyanosilylation of indolizinone 4 into the corresponding cyanohydrin 5 , mediated by a bifunctional thiourea‐based cinchona alkaloid under mild conditions, and I 2 ‐catalyzed Friedländer condensation of the tricyclic lactone 6 and 2‐amino‐5‐hydroxy propiophenone (=1‐(2‐amino‐5‐hydroxyphenyl)propan‐1‐one).