A Straightforward Total Synthesis of (-)-Chaetominine. Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] Journal article | | Title | A Straightforward Total Synthesis of (-)-Chaetominine. | | Author(s) | Malgesini B, Forte B, Borghi D, Quartieri F, Gennari C, Papeo G | | Institution | Chemical Core Technologies, Nerviano Medical Sciences, Viale Pasteur 10, 20014 Nerviano (MI) (Italy). | | Source | Chemistry 2009 Jun 27. | | Abstract | A total synthesis of the tripeptide alkaloid (-)-chaetominine (1) was achieved in 9.3 % overall yield starting from commercially available D-tryptophan methyl ester, based on a short and straightforward (nine steps) sequence. The early stage introduction (first step) of the quinazolinone moiety and the late stage introduction (penultimate step) of the hydroxy group allowed a synthetic strategy devoid of protective groups. The key step of the process is the a-c tricyclic ring construction via an unprecedented NCS-mediated N-acyl cyclization on an indole ring to give tetrahydro-1H-pyrido[2,3-b]indole 11. In the penultimate step, oxidation of the tetracyclic intermediate 14 with oxaziridine 15 gave only one of the four possible diastereoisomers, the cis-diastereoisomer 16 resulting from the attack of the oxaziridine to the double bond face opposite to the c-d ring substituents. In the last step, the complete stereocontrol of the Et(3)SiH/TFA reduction of compound 16, probably involving a N-acyliminium ion, can be attributed to ring constrain, which forces the b-c ring junction in the more stable cis-orientation. (-)-Chaetominine (1) showed a negligible inhibitory activity on several cancer cell lines. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19562787 |
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