Stereoselective total synthesis and enantioselective formal synthesis of the antineoplastic sesquiterpene quinone metachromin A

Stereoselective total synthesis and enantioselective formal synthesis of the antineoplastic sesquiterpene quinone metachromin A

The first total synthesis of the antineoplastic marine natural product metachromin-A (1) was accomplished through a convergent synthetic approach amenable to the preparation of analogues for biological studies. The synthesis involved twelve steps in its longest sequence and sixteen steps overall. The total synthesis of the racemic metachromin-A features: (1) an efficient synthesis of the quinone intermediate 11; (2) efficient protocols for the preparation of the key fragments 5 and 6; (3) a highly regioselective Thiele-Winter acetoxylation step; and (4) a stereoselective Horner-Wadsworth-Emmons coupling reaction employing fragment 6 as a non-stabilized phosphonate as an effective partner. The metachromin-A synthesis was made formally enantioselective by the asymmetric synthesis of fragment 5 employing the methodologies developed by Simpkins (asymmetric deprotonation with a chiral nitrogenated base) and d’Angelo (enantioselective deracemization). This latter protocol furnished fragment 5 with an enantiomeric excess of ~85%, as determined by ¹H-NMR spectroscopy.

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Main Authors: Almeida,Wanda P., Correia,Carlos Roque D.
Format: Digital revista
Language:English
Published: Sociedade Brasileira de Química 1999
Online Access:http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50531999000500011
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spelling oai:scielo:S0103-505319990005000112001-06-07Stereoselective total synthesis and enantioselective formal synthesis of the antineoplastic sesquiterpene quinone metachromin AAlmeida,Wanda P.Correia,Carlos Roque D. metachromin A sesquiterpene quinones total synthesis enantioselective synthesis The first total synthesis of the antineoplastic marine natural product metachromin-A (1) was accomplished through a convergent synthetic approach amenable to the preparation of analogues for biological studies. The synthesis involved twelve steps in its longest sequence and sixteen steps overall. The total synthesis of the racemic metachromin-A features: (1) an efficient synthesis of the quinone intermediate 11; (2) efficient protocols for the preparation of the key fragments 5 and 6; (3) a highly regioselective Thiele-Winter acetoxylation step; and (4) a stereoselective Horner-Wadsworth-Emmons coupling reaction employing fragment 6 as a non-stabilized phosphonate as an effective partner. The metachromin-A synthesis was made formally enantioselective by the asymmetric synthesis of fragment 5 employing the methodologies developed by Simpkins (asymmetric deprotonation with a chiral nitrogenated base) and d’Angelo (enantioselective deracemization). This latter protocol furnished fragment 5 with an enantiomeric excess of ~85%, as determined by ¹H-NMR spectroscopy.info:eu-repo/semantics/openAccessSociedade Brasileira de QuímicaJournal of the Brazilian Chemical Society v.10 n.5 19991999-10-01info:eu-repo/semantics/articletext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50531999000500011en10.1590/S0103-50531999000500011
institution SCIELO
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country Brasil
countrycode BR
component Revista
access En linea
databasecode rev-scielo-br
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region America del Sur
libraryname SciELO
language English
format Digital
author Almeida,Wanda P.
Correia,Carlos Roque D.
spellingShingle Almeida,Wanda P.
Correia,Carlos Roque D.
Stereoselective total synthesis and enantioselective formal synthesis of the antineoplastic sesquiterpene quinone metachromin A
author_facet Almeida,Wanda P.
Correia,Carlos Roque D.
author_sort Almeida,Wanda P.
title Stereoselective total synthesis and enantioselective formal synthesis of the antineoplastic sesquiterpene quinone metachromin A
title_short Stereoselective total synthesis and enantioselective formal synthesis of the antineoplastic sesquiterpene quinone metachromin A
title_full Stereoselective total synthesis and enantioselective formal synthesis of the antineoplastic sesquiterpene quinone metachromin A
title_fullStr Stereoselective total synthesis and enantioselective formal synthesis of the antineoplastic sesquiterpene quinone metachromin A
title_full_unstemmed Stereoselective total synthesis and enantioselective formal synthesis of the antineoplastic sesquiterpene quinone metachromin A
title_sort stereoselective total synthesis and enantioselective formal synthesis of the antineoplastic sesquiterpene quinone metachromin a
description The first total synthesis of the antineoplastic marine natural product metachromin-A (1) was accomplished through a convergent synthetic approach amenable to the preparation of analogues for biological studies. The synthesis involved twelve steps in its longest sequence and sixteen steps overall. The total synthesis of the racemic metachromin-A features: (1) an efficient synthesis of the quinone intermediate 11; (2) efficient protocols for the preparation of the key fragments 5 and 6; (3) a highly regioselective Thiele-Winter acetoxylation step; and (4) a stereoselective Horner-Wadsworth-Emmons coupling reaction employing fragment 6 as a non-stabilized phosphonate as an effective partner. The metachromin-A synthesis was made formally enantioselective by the asymmetric synthesis of fragment 5 employing the methodologies developed by Simpkins (asymmetric deprotonation with a chiral nitrogenated base) and d’Angelo (enantioselective deracemization). This latter protocol furnished fragment 5 with an enantiomeric excess of ~85%, as determined by ¹H-NMR spectroscopy.
publisher Sociedade Brasileira de Química
publishDate 1999
url http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50531999000500011
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AT correiacarlosroqued stereoselectivetotalsynthesisandenantioselectiveformalsynthesisoftheantineoplasticsesquiterpenequinonemetachromina
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