A Stereodivergent Strategy for the Preparation of Corynantheine and Ipecac Alkaloids, Their Epimers, and Analogues: Efficient Total Synthesis of ()- Dihydrocorynantheol, ()-Corynantheol, ()-Protoemetinol, ()- Corynantheal, ()-Protoemetine, and Related Natural and Nonnatural Compound
2011 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 17, no 49, 13814-13824 p.Article in journal (Refereed) Published
Abstract: Here we present a general and common catalytic asymmetric strategy for the total and formal synthesis of a broad number of optically active natural products from the corynantheine and ipecac alkaloid families, for example, indoloACHTUNGTRENUNG[2,3-a]- and benzo[a]quinolizidines. Construction of the core alkaloid skeletons with the correct absolute and relative stereochemistry relies on an enantioselective and diastereodivergent one-pot cascade sequence followed by an additional diastereodivergent reaction step. This allows for enantio- and diastereoselective synthesis of three out of four possible epimers of the quinolizidine alkaloids that begin from common and easily accessible starting materials by using a common synthetic route. Focus has been made on excluding protecting groups and limiting isolation and purification of synthetic intermediates. This methodology is applied in the total synthesis of the natural products ()-dihydrocorynantheol, ()-hirsutinol, ()-corynantheol, ()-protometinol, ()-dihydrocorynantheal, ()-corynantheal, ()-protoemetine, ()-(15S)-hydroxydihydrocorynantheol, and an array of their nonnatural epimers. The potential of this strategy is also demonstrated in the synthesis of biologically interesting natural product analogues not accessible through synthetic elaboration of alkaloid precursors available from nature, for example, thieno[3,2-a]quinolizidine derivatives. We also report the formal synthesis of (+)-dihydrocorynantheine, ()-emetine, ()-cephaeline, ()-tubulosine, and ()-deoxytubulosine.
Place, publisher, year, edition, pages
2011. Vol. 17, no 49, 13814-13824 p.
alkaloids · asymmetric catalysis · diastereodivergency · natural products · total synthesis
IdentifiersURN: urn:nbn:se:kth:diva-79167DOI: 10.1002/chem.201102012ISI: 000298060800028ScopusID: 2-s2.0-82455192855OAI: oai:DiVA.org:kth-79167DiVA: diva2:495193
FunderSwedish Research Council
QC 201202092012-02-082012-02-082014-04-25Bibliographically approved