- Carbon-13 NMR of citrinin in the solid state and in solutions
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Carbon-13 NMR is used to study the tautomeric equilibrium of citrinin in the solid state. The results confirm earlier X-ray diffraction studies, which indicated that the compound crystallizes in a disordered structure, with the p-quinone and o-quinone forms in a dynamic equilibrium. Analysis of the NMR data yields the equilibrium constant K(T) = [o]/[p] = exp(4.2/R) exp(-1610/RT) (where R is in cal mol-1 K-1), which is essentially identical to that determined by X-ray. The tautomerism is extremely fast on the NMR time scale (> 106 s-1). In methylene chloride solution citrinin also exists as a fast interconverting mixture of the two isomers with an equilibrium constant K ～ 0.7 at room temperature. However, the temperature dependence of the carbon-13 and oxygen-17 chemical shifts gave conflicting results, thus preventing a reliable determination of the thermodynamic parameters of K. In methanol and methanol/methylene chloride mixtures, citrinin undergoes a nucleophilic, Michael type, addition. The reaction is reversible, and the equilibrium shifts toward the normal cirtrinin form upon increasing temperature and in methanol/methylene chloride mixtures with increasing methylene chloride fraction. Only normal citrinin is obtained on crystallization, even from neat methanol.
- Poupko,Luz,Destro
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- Enantioselective Synthesis of the Polyketide Antibiotic (3R,4S)-(-)-Citrinin
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The fungal metabolite (-)-citrinin (1) was synthesized for the first time.Reaction of the Grignard reagent of 2,4-bis(benzyloxy)-6-bromotoluene (3) with (2S)-trans-(-)-2,3-dimethyloxirane (6) in the presence of 1,5-cyclooctadienecopper(I) chloride as catalyst leads to the formation of (2S,3S)-(-)-7 with erythro configuration.Compound (-)-7 could be transformed into (2R,3S)-(-)-9 with threo configuration via the formate (1R,2S)-(+)-8 by a Mitsunobu reaction.Reaction of the Grignard reagent of 3 with the achiral cis-2,3-dimethyl-oxirane yielded directly (+/-)-9.The starting material 3 was readily available from 1,3-bis(benzyloxy)-5-bromobenzene (4).Formylation of 4 furnished the aldehyde 5 which could be reduced to 3 with borane.Hydrogenolysis of the benzyl ether groups in (-)-9 gave (-)-2 with threo configuration.The remaining steps to produce citrinin from (-)-2 required carboxylation to 11, formylation and in situ ring closure with ethyl orthoformate to produce the required quinomethide structure.Application of the same reactions to (+/-)-9 and (+/-)-2 afforded (+/-)-citrinin in 40percent overall yield. - Key Words: Citrinin, (3R,4S)-(-)- / 2,3-Dimethyloxirane, trans-(-)- and cis- / Synthesis of erythro- and threo-3-arylbutan-2-ols
- Roedel, Thomas,Gerlach, Hans
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p. 885 - 888
(2007/10/02)
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- A Diastereoselective Synthesis of the Polyketide Antibiotic Citrinin using Toluate Anion Chemistry
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The diastereoselectivity of various synthetic approaches to (+/-)-threo-3-(3,5-dihydroxy-2-methylphenyl)butan-2-ol ('Phenol B') (4), based on reactions of benzyl anions with electrophiles, has been investigated.The anion (9) derived from ethyl 2,4-dimethoxy-6-ethylbenzoate reacted with acetaldehyde to give mainly an erythro-product isolated as the lactone (12); acetylation with acetyl chloride to give a ketone, followed by reduction, gave mainly the required threo-lactone (11).An alternative route was frustrated by decomposition of the benzyl anion derived from 3,4-dihydro-6,8-dimethoxy-3-methyl-1H-2-benzopyran-1-one (17).Reduction of the carbonyl group of the threo-lactone (11) to a methyl gave the dimethyl ether of 'Phenol B', which was converted into (+/-)-citrinin (1).
- Barber, Jill A.,Staunton, James,Wilkinson, Michael R.
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p. 2101 - 2110
(2007/10/02)
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