Total Synthesis of Phorbazole B.

Yngve Guttormsen,Annette Bayer,Sunil K Pandey,Johan Isaksson,Magnus E Fairhurst,Bengt Erik Haug

doi:10.3390/molecules25204848

Yngve Guttormsen, Annette Bayer + Show 4 more

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https://doi.org/10.3390/molecules25204848

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Abstract

Phorbazoles are polychlorinated heterocyclic secondary metabolites isolated from a marine sponge and several of these natural products have shown inhibitory activity against cancer cells. In this work, a synthesis of the trichlorinated phorbazole B using late stage electrophilic chlorination was developed. The synthesis relied on the use of an oxazole precursor, which was protected with an iodine in the reactive 4-position, followed by complete chlorination of all pyrrole positions. Attempts to prepare phorbazole A and C, which contain a 3,4-dichlorinated pyrrole, were unsuccessful as the desired chlorination pattern on the pyrrole could not be obtained. The identities of the dichlorinated intermediates and products were determined using NMR techniques including NOESY/ROESY, 1,1-ADEQUATE and high-resolution CLIP-HSQMBC.

Highlights

IntroductionPhorbazoles A–D (1–4, Figure 1) are polychlorinated heterocyclic secondary metabolites isolatedPhorbazoles A–D (1–4, Figure 1) are polychlorinated heterocyclic secondary metabolites isolated from thefrom marine spongePhorbas aff. aff.Clathrata ofSouth SouthAfrica in 1994 the marine sponge PhorbasClathrataoff offthe the coast coast of Africa in 1994 [1]. [1]
Phorbazoles A–D (1–4, Figure 1) are polychlorinated heterocyclic secondary metabolites isolated from thefrom marine sponge
We report the total synthesis of 2 via late-stage chlorination and attempts at synthesizing

Summary

Introduction

Phorbazoles A–D (1–4, Figure 1) are polychlorinated heterocyclic secondary metabolites isolatedPhorbazoles A–D (1–4, Figure 1) are polychlorinated heterocyclic secondary metabolites isolated from thefrom marine spongePhorbas aff. aff.Clathrata ofSouth SouthAfrica in 1994 the marine sponge PhorbasClathrataoff offthe the coast coast of Africa in 1994 [1]. [1]. Phorbazoles A–D (1–4, Figure 1) are polychlorinated heterocyclic secondary metabolites isolated. Phorbazoles A–D (1–4, Figure 1) are polychlorinated heterocyclic secondary metabolites isolated from thefrom marine sponge. Africa in 1994 the marine sponge Phorbas. Clathrataoff offthe the coast coast of Africa in 1994 [1].

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