Efficient oxidative cyclization of 1,6-dienes: a highly diastereoselective entry to substituted tetrahydropyrans.
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Journal Article↗
Biomedical subjects
Christian B W Stark
Publications and source records attributed to Christian B W Stark.
Total synthesis of cis-solamin: exploiting the RuO4-catalyzed oxidative cyclization of dienes.
[structure: see text] An enantioselective total synthesis of cis-solamin has been accomplished using a highly diastereoselective ruthenium tetroxide catalyzed oxidative cyclization as a crucial transformation. Further key steps involved an enzymatic desymmetrization, a TPAP-catalyzed oxidative termini differentiation, and a ruthenium-catalyzed Alder-ene reaction. Thus, the total synthesis of cis-solamin was achieved in 11 steps with an overall yield of 7.5%.
Annonaceae↗
Evidence for the role of the monB genes in polyether ring formation during monensin biosynthesis.
Ionophoric polyethers are produced by the exquisitely stereoselective oxidative cyclization of a linear polyketide, probably via a triepoxide intermediate. We report here that deletion of either or both of the monBI and monBII genes from the monensin biosynthetic gene cluster gave strains that produced, in place of monensins A and B, a mixture of C-3-demethylmonensins and a number of minor components, including C-9-epi-monensin A. All the minor components were efficiently converted into monensins by subsequent acid treatment. These data strongly suggest that epoxide ring opening and concomitant polyether ring formation are catalyzed by the MonB enzymes, rather than by the enzyme MonCII as previously thought. Consistent with this, homology modeling shows that the structure of MonB-type enzymes closely resembles the recently determined structure of limonene-1,2-epoxide hydrolase from Rhodococcus erythropolis.
Amino Acid Sequence↗
Accumulation of an E,E,E-triene by the monensin-producing polyketide synthase when oxidative cyclization is blocked.
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Cyclization↗
Evidence for gas-phase redox chemistry inducing novel fragmentation in a complex natural product.
The fragmentation of monensin A, in the presence of calcium, barium, silver and copper salts was studied by electrospray ionisation tandem accurate-mass mass spectrometry. The results showed that the calcium, barium and silver complexes of monensin A showed no significant alteration in their fragmentation to that previously observed for the sodium salts. However, the fragmentation of the copper(ii) salt resulted in new fragmentation routes. We propose that the copper might be initiating a novel gas-phase redox reaction resulting in a series of highly diagnostic ions. This methodology is demonstrated by locating the change in structure between the naturally occurring analogues monensin A and B.
Barium↗
The effect of ruthenium(III) chloride on the formation of protonated parent ions in electrospray mass spectrometry.
We report the use of RuCl3 as an "alkali metal sponge". This is a general and highly efficient method for generating protonated parent ions for a variety of compounds that usually do not show this ion in electrospray mass spectrometry. This technique is demonstrated to be highly useful in "cleaning up" spectra from multiply metallated ions, thereby substantially improving the signal-to-noise ratio.
Cyclodextrins↗
Intermediates released from a polyether-producing polyketide synthase provide insight into the mechanism of oxidative cyclization.
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Cyclization↗
Sesquiterpene lactones from Lychnophora ericoides.
Two new sesquiterpene lactones, (4S,6R,7S,8S,10R,11S,16R)-1-oxo-3(10),8(16)-diepoxy-16-methylprop-1Z-enyl-16-methoxygermacra-2-en-6(12)-olide (1) and (4S,6R,7S,8S,10R,11S)-1-oxo-3,10-epoxy-8-angeloyloxygermacra-2-en-6(12)-olide (2), were isolated from Lychnophora ericoides. Their structures, including absolute configuration, were established by spectroscopic methods, including single-crystal X-ray analysis. Monitoring the furanoheliangolide metabolism of L. ericoides revealed an increase in biosynthesis during the plant flowering period.
Asteraceae↗
Analysis of the biosynthetic gene cluster for the polyether antibiotic monensin in Streptomyces cinnamonensis and evidence for the role of monB and monC genes in oxidative cyclization.
The analysis of a candidate biosynthetic gene cluster (97 kbp) for the polyether ionophore monensin from Streptomyces cinnamonensis has revealed a modular polyketide synthase composed of eight separate multienzyme subunits housing a total of 12 extension modules, and flanked by numerous other genes for which a plausible function in monensin biosynthesis can be ascribed. Deletion of essentially all these clustered genes specifically abolished monensin production, while overexpression in S. cinnamonensis of the putative pathway-specific regulatory gene monR led to a fivefold increase in monensin production. Experimental support is presented for a recently-proposed mechanism, for oxidative cyclization of a linear polyketide intermediate, involving four enzymes, the products of monBI, monBII, monCI and monCII. In frame deletion of either of the individual genes monCII (encoding a putative cyclase) or monBII (encoding a putative novel isomerase) specifically abolished monensin production. Also, heterologous expression of monCI, encoding a flavin-linked epoxidase, in S. coelicolor was shown to significantly increase the ability of S. coelicolor to epoxidize linalool, a model substrate for the presumed linear polyketide intermediate in monensin biosynthesis.
Base Sequence↗
Fragmentation studies on monensin A and B by accurate-mass electrospray tandem mass spectrometry.
Monensin A and B were studied by electrospray ionisation tandem mass spectrometry (ESI-MS/MS) and the fragment ions were confirmed by accurate-mass measurements. Analyses were performed on both a quadrupole time-of-flight (QTOF) and a Fourier-transform ion cyclotron resonance (FTICR) mass spectrometer. The analysis revealed that fragment ions were produced by Grob-Wharton fragmentations and pericyclic rearrangements in addition to various simple neutral losses. A study of the protonated and sodiated sodium salt revealed different fragmentation pathways for these species, thus complementary structural information could be gained. A complete fragmentation pathway of monensin A and B protonated sodium salt [(M-H+Na)+H])+) and sodiated sodium salt [(M-H+Na)+Na](+) is proposed. MS(3) analysis confirmed the separate fragmentation pathways.
Chromatography, High Pressure Liquid↗
Fragmentation studies on monensin A by sequential electrospray mass spectrometry.
Monensin A was studied by electrospray ionisation sequential mass spectrometry (ESI-MSn) and all fragments were confirmed by accurate-mass measurements. Analyses were performed on both a quadrupole time-of-flight (Q-tof) and a Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometer. MSn analysis shows that depending on sample preparation the ion at m/z 671 consists of two different ions with the same accurate-mass. It is either the monensin protonated parent ion or a different ion structure derived from the loss of water from the water adduct of monensin. Both ions show different fragmentation patterns. Major fragment ions from the protonated parent ion were produced by Grob-Wharton type fragmentations in addition to various simple neutral losses. The fragmentation pathways of the two different m/z 671 ions are proposed.
Gas Chromatography-Mass Spectrometry↗