29394-61-4Relevant articles and documents
The divergent asymmetric synthesis of kalafungin, 5-epi-frenolicin B and related pyranonaphthoquinone antibiotics
Donner, Christopher D.
, p. 377 - 386 (2013/01/15)
A divergent, asymmetric method for the synthesis of pyranonaphthoquinones is reported. The synthetic strategy applies a Staunton-Weinreb annulation between substituted ortho-toluates and the (R)-pyran-2-one 7 to construct the key naphthopyranone intermediates. Stereoselective introduction of either a methyl or propyl C5 alkyl substituent by use of Grignard addition/silane- mediated reduction and a sequence of oxidations gave a series of pyranonaphthoquinones including kalafungin 1, 5-epi-9-methoxykalafungin 34 and 5-epi-frenolicin B 24.
Total synthesis of (+)-kalafungin using a tandem Michael-Dieckmann approach
Donner, Christopher D.
, p. 8888 - 8890 (2008/03/30)
A stereoselective synthesis of the antibiotic kalafungin 1 is reported. A key step involved the tandem Michael-Dieckmann reaction between methyl 2-methoxy-6-methylbenzoate 11 and the α,β-unsaturated lactone (R)-6-(2-(tert-butyldimethylsilyloxy)ethyl)-4-methoxy-5,6-dihydropyran-2-one 10, which was prepared from (S)-aspartic acid. The C5 alkyl substituent was introduced by the use of methylmagnesium bromide and subsequent stereoselective reduction. A sequence of oxidations followed by acid-catalyzed epimerization delivered (+)-kalafungin 1.
Reactions of semiquinones in aqueous solution. A comparison of the one electron reduction of kalafungin and analogues with other semiquinones using pulse radiolysis
Anderson, Robert F.,Brimble, Margaret A.,Nairn, Michael R.,Packer, John E.
, p. 475 - 479 (2007/10/03)
The radical anions of the pyranonaphthoquinone antibiotic kalafungin 1 and analogues have been studied in aqueous solution by pulse radiolysis using transient absorption spectrophotometry. Radical absorption spectra were similar regardless of the nature of the substituent at C-5 or C-7 and the decay followed second-order kinetics showing any potential first-order ring opening was too slow to compete with bimolecular disproportionation at the concentration of radicals produced by pulse radiolysis. Spectral studies using steady-state radiolysis confirmed the absence of ring opening. The pKa of each of the semiquinones of compounds 1-5 were determined and whereas replacing a hydrogen at C-7 by a methoxy, 2 and 4, raises the pKa by 2.5-2.9 units demonstrating a significant substituent effect, no such increase occurs for OH, 1. This and the fact that kalafungin, 1, has the most positive one-electron reduction potential E(1), -63 ± 10 mV in neutral solution, is attributed to H-bonding between the 7-OH and the oxygen of the semiquinone, with the H-bonding effectively nullifying the substituent effect. The presence of an OH on C-5 has a much less significant effect on the E(1) and pKa values. Comparison of kinetics and products in systems with and without tert-butanol brings into question a report that 2-(methoxymethyl)benzo1,4-quinone and 2-(phenoxymethyl)benzo-1,4-quinone undergo dissociation on one-electron reduction.
