Limits...
Turning Spiroketals Inside Out: A Rearrangement Triggered by an Enol Ether Epoxidation.

Lorenc C, Saurí J, Moser A, Buevich AV, Williams AJ, Williamson RT, Martin GE, Peczuh MW - ChemistryOpen (2015)

Bottom Line: Here we describe rearrangements of those compounds, triggered by epoxidation of their enol ethers that completely remodel their structures, essentially turning them "inside out".Solution of the structures of the representative compounds allowed for the assignment of product structures for the other compounds in two separate series.Both the rearrangement and the methods used for structural determination of the products are valuable tools for the preparation of characterization of new small molecule compounds.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Connecticut 55 N. Eagleville Road, U3060, Storrs, CT, 06269, USA.

ABSTRACT
Spiroketals organize small molecule structures into well-defined, three-dimensional configurations that make them good ligands of proteins. We recently discovered a tandem cycloisomerization-dimerization reaction of alkynyl hemiketals that delivered polycyclic, enol-ether-containing spiroketals. Here we describe rearrangements of those compounds, triggered by epoxidation of their enol ethers that completely remodel their structures, essentially turning them "inside out". Due to the high level of substitution on the carbon skeletons of the substrates and products, characterization resorted to X-ray crystallography and advanced computation and NMR techniques to solve the structures of representative compounds. In particular, a new proton-detected ADEQUATE NMR experiment (1,1-HD-ADEQUATE) enabled the unequivocal assignment of the carbon skeleton of one of the new compounds. Solution of the structures of the representative compounds allowed for the assignment of product structures for the other compounds in two separate series. Both the rearrangement and the methods used for structural determination of the products are valuable tools for the preparation of characterization of new small molecule compounds.

No MeSH data available.


Crystal structure of rearranged spiroketal 7.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4608522&req=5

fig02: Crystal structure of rearranged spiroketal 7.

Mentions: Data from a series of NMR spectra (1H, 13C, COSY, HSQC, HMBC) provided clues about the structure of the new compound. For example, the presence of signals corresponding to six ketal/hemi-ketal carbons and the absence of a ketone carbonyl carbon revealed that the ketone in the starting material was pyramidalized at some point during the reaction. This, together with signals corresponding to the m-chlorobenzoyl group, suggested that m-chlorobenzoic acid had added into an oxocarbenium ion en route to the product. HMBC correlations suggested a skeletal structure containing fused and spirocyclic rings but assembling the fragments of data into an overall structure was problematic. For example, the exact locations of the hemi-ketal and the acylated ketal were uncertain. A sample of the compound ultimately yielded crystals suitable for X-ray diffraction experiments and its structure, 7, is shown in Figure 2 and Table 1. The product spiroketal consisted of a highly congested, polycyclic core onto which the m-chlorobenzoyl unit was attached. The core itself contained six contiguously fused rings, one that contains two spiroketal carbons and another that has one ketal and one hemi-ketal carbon. The structure, when compared to that of the starting material, showed that a total rearrangement of the spiroketal had occurred. The spiroketal in 313 was of the variety where both linkages contained anomeric relationships.2 Product 7, in contrast, contained two spiroketals, each with one anomeric and one nonanomeric relationship. The contributions of these stereoelectronic effects, while substantial to the stability of a compound, must be balanced with other factors such as steric effects. The new spiroketals balanced these interactions and stabilized the congested molecules while at the same time minimizing steric interactions. Having gained insight on the structure of the product, we examined the scope of the reaction using other reagents (peracetic acid) and substrates (5 and 6) to explore its generality (Table 1). Product structures 8–10 were assigned from the similarity of their NMR spectra in comparison to 7.


Turning Spiroketals Inside Out: A Rearrangement Triggered by an Enol Ether Epoxidation.

Lorenc C, Saurí J, Moser A, Buevich AV, Williams AJ, Williamson RT, Martin GE, Peczuh MW - ChemistryOpen (2015)

Crystal structure of rearranged spiroketal 7.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608522&req=5

fig02: Crystal structure of rearranged spiroketal 7.
Mentions: Data from a series of NMR spectra (1H, 13C, COSY, HSQC, HMBC) provided clues about the structure of the new compound. For example, the presence of signals corresponding to six ketal/hemi-ketal carbons and the absence of a ketone carbonyl carbon revealed that the ketone in the starting material was pyramidalized at some point during the reaction. This, together with signals corresponding to the m-chlorobenzoyl group, suggested that m-chlorobenzoic acid had added into an oxocarbenium ion en route to the product. HMBC correlations suggested a skeletal structure containing fused and spirocyclic rings but assembling the fragments of data into an overall structure was problematic. For example, the exact locations of the hemi-ketal and the acylated ketal were uncertain. A sample of the compound ultimately yielded crystals suitable for X-ray diffraction experiments and its structure, 7, is shown in Figure 2 and Table 1. The product spiroketal consisted of a highly congested, polycyclic core onto which the m-chlorobenzoyl unit was attached. The core itself contained six contiguously fused rings, one that contains two spiroketal carbons and another that has one ketal and one hemi-ketal carbon. The structure, when compared to that of the starting material, showed that a total rearrangement of the spiroketal had occurred. The spiroketal in 313 was of the variety where both linkages contained anomeric relationships.2 Product 7, in contrast, contained two spiroketals, each with one anomeric and one nonanomeric relationship. The contributions of these stereoelectronic effects, while substantial to the stability of a compound, must be balanced with other factors such as steric effects. The new spiroketals balanced these interactions and stabilized the congested molecules while at the same time minimizing steric interactions. Having gained insight on the structure of the product, we examined the scope of the reaction using other reagents (peracetic acid) and substrates (5 and 6) to explore its generality (Table 1). Product structures 8–10 were assigned from the similarity of their NMR spectra in comparison to 7.

Bottom Line: Here we describe rearrangements of those compounds, triggered by epoxidation of their enol ethers that completely remodel their structures, essentially turning them "inside out".Solution of the structures of the representative compounds allowed for the assignment of product structures for the other compounds in two separate series.Both the rearrangement and the methods used for structural determination of the products are valuable tools for the preparation of characterization of new small molecule compounds.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Connecticut 55 N. Eagleville Road, U3060, Storrs, CT, 06269, USA.

ABSTRACT
Spiroketals organize small molecule structures into well-defined, three-dimensional configurations that make them good ligands of proteins. We recently discovered a tandem cycloisomerization-dimerization reaction of alkynyl hemiketals that delivered polycyclic, enol-ether-containing spiroketals. Here we describe rearrangements of those compounds, triggered by epoxidation of their enol ethers that completely remodel their structures, essentially turning them "inside out". Due to the high level of substitution on the carbon skeletons of the substrates and products, characterization resorted to X-ray crystallography and advanced computation and NMR techniques to solve the structures of representative compounds. In particular, a new proton-detected ADEQUATE NMR experiment (1,1-HD-ADEQUATE) enabled the unequivocal assignment of the carbon skeleton of one of the new compounds. Solution of the structures of the representative compounds allowed for the assignment of product structures for the other compounds in two separate series. Both the rearrangement and the methods used for structural determination of the products are valuable tools for the preparation of characterization of new small molecule compounds.

No MeSH data available.