Issue 10, 2003

Synthesis of 3-azido-2,3,6-trideoxy-β-d-arabino-hexopyranosyl pyranonaphthoquinone analogues of medermycin

Abstract

The synthesis of an isomeric mixture of 4-O-acetyl-3-azido-2,3,6-trideoxy-β-D-arabino-hexopyranosyl analogues 6 of the C-glycosylpyranonaphthoquinone antibiotic medermycin is described. The key 3-acetyl-6-(4-O-acetyl-3-azido-2,3,6-trideoxy-β-D-arabino-hexopyranosyl)-5-methoxy-1,4-naphthoquinone 8 was prepared via Stille coupling of 6-(3-azido-2,3,6-trideoxy-β-D-arabino-hexopyranosyl)-3-bromo-1,4-naphthoquinone 17 with (α-ethoxyvinyl)tributylstannane followed by hydrolysis and oxidation of the resultant hydroquinone 18. Bromonaphthoquinone 17 in turn was afforded by oxidative demethylation of 6-(4-O-acetyl-3-azido-2,3,6-trideoxy-β-D-arabino-hexopyranosyl)-3-bromo-1,4,5-trimethoxynaphthalene 16 formed by regioselective bromination of 6-(4-acetyl-3-azido-2,3,6-trideoxy-β-D-arabino-hexopyranosyl)-1,4,5-trimethoxynaphthalene 10. This latter naphthalene 10 was prepared via direct C-glycosylation of naphthol 12 with glycosyl donor 11 using BF3·Et2O in acetonitrile. The regioselectivity of the bromination of naphthalene 10 was independently determined by reductive monomethylation of the 6-(4-O-acetyl-3-azido-2,3,6-trideoxy-β-D-arabino-hexopyranosyl)-5-methoxy-1,4-naphthoquinone 22 to naphthol 23 followed by selective ortho bromination to bromide 24 and methylation to 16. Attempts to effect acetylation of 6-(4-O-acetyl-3-azido-2,3,6-trideoxy-β-D-arabino-hexopyranosyl)-3-bromo-1,4,5-trimethoxynaphthalene 16 and 3-bromo-6-(3-dimethylamino-2,3,6-trideoxy-β-D-arabino-hexopyranosyl)-1,4,5-trimethoxynaphthalene 26via Stille coupling with (α-ethoxyvinyl)tributylstannane were low yielding thereby establishing the necessity to use an azido group as a latent dimethylamino group and a more electrophilic bromonaphthoquinone as the coupling partner for the Stille reaction. Addition of 2-trimethylsilyloxyfuran 9 to 3-acetyl-6-(4-O-acetyl-3-azido-2,3,6-trideoxy-β-D-arabino-hexopyranosyl)-5-methoxy-1,4-naphthoquinone 8 afforded the furofuran adducts 7 and 19 as an inseparable mixture of diastereomers. Oxidative rearrangement of this diastereomeric mixture using ceric ammonium nitrate afforded the inseparable diastereomeric furonaphthopyrans 6 and 20.

Graphical abstract: Synthesis of 3-azido-2,3,6-trideoxy-β-d-arabino-hexopyranosyl pyranonaphthoquinone analogues of medermycin

Article information

Article type
Paper
Submitted
05 Feb 2003
Accepted
31 Mar 2003
First published
11 Apr 2003

Org. Biomol. Chem., 2003,1, 1690-1700

Synthesis of 3-azido-2,3,6-trideoxy-β-D-arabino-hexopyranosyl pyranonaphthoquinone analogues of medermycin

M. A. Brimble, R. M. Davey, M. D. McLeod and M. Murphy, Org. Biomol. Chem., 2003, 1, 1690 DOI: 10.1039/B301449P

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements