A new synthesis of (-)-anisomycin and its demethoxy analogue from D-ribose

J. Grant Buchanan, Keith A. MacLean, Richard H. Wightman, Hans Paulsen

Research output: Contribution to journalArticle

Abstract

2,3-O-Isopropylidene-D-ribose (7) reacted with p-methoxybenzylmagnesium chloride in tetrahydrofuran to give the D-allotriol (6a) (77%). Periodate oxidation of compound (6a) followed by reaction with hydroxylamine hydrochloride in pyridine gave (E,Z)-5-deoxy-2,3-O-isopropylidene-5-(p-methoxy-phenyl)-L- ribose oxime (18a) which was converted into the nitrile methanesulphonate (19a) with methanesulphonyl chloride in pyridine. Reduction of the nitrile (19a) with lithium aluminium hydride gave (2R,3S,4R)-3,4-isopropylidenedioxy-2-(p- methoxybenzyl)pyrrolidine (2a) [45% from (6a)], which was converted into the epoxide (24a) (68%) via the bromo acetates (28a) and (29a). Regioselective opening of the epoxide ring in compound (24a) with acidic allyl alcohol gave the allyl ether (30a) (63%) which was converted into the N-benzyl 3-acetoxy compound (31a) (77%). Removal of the allyl and benzyl groups, by treatment with palladium-charcoal under acidic conditions followed by hydrogenolysis, gave (-)-anisomycin (1a) (86%). A similar series of reactions afforded demethoxyanisomycin (1b) which showed antibiotic activity against Trichomonas vaginalis [about one sixth the activity of anisomycin (1a)].

Original languageEnglish
Pages (from-to)1463-1470
Number of pages8
JournalJournal of the Chemical Society, Perkin Transactions 1
Publication statusPublished - 1985

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Anisomycin
Nitriles
Ribose
Epoxy Compounds
Chlorides
Hydrogenolysis
Hydroxylamine
Oximes
Charcoal
Palladium
Ether
Acetates
Anti-Bacterial Agents
Oxidation
propylene
pyridine
allyl alcohol
lithium aluminum hydride
pyrrolidine
metaperiodate

Cite this

Buchanan, J. G., MacLean, K. A., Wightman, R. H., & Paulsen, H. (1985). A new synthesis of (-)-anisomycin and its demethoxy analogue from D-ribose. Journal of the Chemical Society, Perkin Transactions 1, 1463-1470.
Buchanan, J. Grant ; MacLean, Keith A. ; Wightman, Richard H. ; Paulsen, Hans. / A new synthesis of (-)-anisomycin and its demethoxy analogue from D-ribose. In: Journal of the Chemical Society, Perkin Transactions 1. 1985 ; pp. 1463-1470.
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abstract = "2,3-O-Isopropylidene-D-ribose (7) reacted with p-methoxybenzylmagnesium chloride in tetrahydrofuran to give the D-allotriol (6a) (77{\%}). Periodate oxidation of compound (6a) followed by reaction with hydroxylamine hydrochloride in pyridine gave (E,Z)-5-deoxy-2,3-O-isopropylidene-5-(p-methoxy-phenyl)-L- ribose oxime (18a) which was converted into the nitrile methanesulphonate (19a) with methanesulphonyl chloride in pyridine. Reduction of the nitrile (19a) with lithium aluminium hydride gave (2R,3S,4R)-3,4-isopropylidenedioxy-2-(p- methoxybenzyl)pyrrolidine (2a) [45{\%} from (6a)], which was converted into the epoxide (24a) (68{\%}) via the bromo acetates (28a) and (29a). Regioselective opening of the epoxide ring in compound (24a) with acidic allyl alcohol gave the allyl ether (30a) (63{\%}) which was converted into the N-benzyl 3-acetoxy compound (31a) (77{\%}). Removal of the allyl and benzyl groups, by treatment with palladium-charcoal under acidic conditions followed by hydrogenolysis, gave (-)-anisomycin (1a) (86{\%}). A similar series of reactions afforded demethoxyanisomycin (1b) which showed antibiotic activity against Trichomonas vaginalis [about one sixth the activity of anisomycin (1a)].",
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A new synthesis of (-)-anisomycin and its demethoxy analogue from D-ribose. / Buchanan, J. Grant; MacLean, Keith A.; Wightman, Richard H.; Paulsen, Hans.

In: Journal of the Chemical Society, Perkin Transactions 1, 1985, p. 1463-1470.

Research output: Contribution to journalArticle

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T1 - A new synthesis of (-)-anisomycin and its demethoxy analogue from D-ribose

AU - Buchanan, J. Grant

AU - MacLean, Keith A.

AU - Wightman, Richard H.

AU - Paulsen, Hans

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N2 - 2,3-O-Isopropylidene-D-ribose (7) reacted with p-methoxybenzylmagnesium chloride in tetrahydrofuran to give the D-allotriol (6a) (77%). Periodate oxidation of compound (6a) followed by reaction with hydroxylamine hydrochloride in pyridine gave (E,Z)-5-deoxy-2,3-O-isopropylidene-5-(p-methoxy-phenyl)-L- ribose oxime (18a) which was converted into the nitrile methanesulphonate (19a) with methanesulphonyl chloride in pyridine. Reduction of the nitrile (19a) with lithium aluminium hydride gave (2R,3S,4R)-3,4-isopropylidenedioxy-2-(p- methoxybenzyl)pyrrolidine (2a) [45% from (6a)], which was converted into the epoxide (24a) (68%) via the bromo acetates (28a) and (29a). Regioselective opening of the epoxide ring in compound (24a) with acidic allyl alcohol gave the allyl ether (30a) (63%) which was converted into the N-benzyl 3-acetoxy compound (31a) (77%). Removal of the allyl and benzyl groups, by treatment with palladium-charcoal under acidic conditions followed by hydrogenolysis, gave (-)-anisomycin (1a) (86%). A similar series of reactions afforded demethoxyanisomycin (1b) which showed antibiotic activity against Trichomonas vaginalis [about one sixth the activity of anisomycin (1a)].

AB - 2,3-O-Isopropylidene-D-ribose (7) reacted with p-methoxybenzylmagnesium chloride in tetrahydrofuran to give the D-allotriol (6a) (77%). Periodate oxidation of compound (6a) followed by reaction with hydroxylamine hydrochloride in pyridine gave (E,Z)-5-deoxy-2,3-O-isopropylidene-5-(p-methoxy-phenyl)-L- ribose oxime (18a) which was converted into the nitrile methanesulphonate (19a) with methanesulphonyl chloride in pyridine. Reduction of the nitrile (19a) with lithium aluminium hydride gave (2R,3S,4R)-3,4-isopropylidenedioxy-2-(p- methoxybenzyl)pyrrolidine (2a) [45% from (6a)], which was converted into the epoxide (24a) (68%) via the bromo acetates (28a) and (29a). Regioselective opening of the epoxide ring in compound (24a) with acidic allyl alcohol gave the allyl ether (30a) (63%) which was converted into the N-benzyl 3-acetoxy compound (31a) (77%). Removal of the allyl and benzyl groups, by treatment with palladium-charcoal under acidic conditions followed by hydrogenolysis, gave (-)-anisomycin (1a) (86%). A similar series of reactions afforded demethoxyanisomycin (1b) which showed antibiotic activity against Trichomonas vaginalis [about one sixth the activity of anisomycin (1a)].

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