A1 Refereed original research article in a scientific journal
Alnumycins A2 and A3: new inverse-epimeric pairs stereoisomeric to alnumycin A1
Authors: Oja T, Tahtinen P, Dreiack N, Mantsala P, Niemi J, Metsa-Ketela M, Klika KD
Publisher: PERGAMON-ELSEVIER SCIENCE LTD
Publication year: 2012
Journal: Tetrahedron: Asymmetry
Journal name in source: TETRAHEDRON-ASYMMETRY
Journal acronym: TETRAHEDRON-ASYMMETR
Number in series: 9
Volume: 23
Issue: 9
First page : 670
Last page: 682
Number of pages: 13
ISSN: 0957-4166
DOI: https://doi.org/10.1016/j.tetasy.2012.05.001
Abstract
Two new pairs of stereoisomeric alnumycin As, A2 {(2)-(1R,1'RS,4'SR,5'SR)} and A3 {(2)-(1R,1'RS,4'SR,5'RS)}, are described. Similar to alnumycin A1 {(2)-(1R,1'RS,4'RS,5'SR)}, each of these naturally occurring compounds is also a pair of C-1 inverse epimers. The relative configurations of the dioxane ring sidechains were assigned on the basis of H-1 NMR NOE contacts and molecular modeling using density functional theory (DFT) at the M06-2X/6-31G(d) level of theory. The absolute configurations of C-1 and the determination of inverse epimeric relationships were achieved by experimental electronic circular dichroism (ECD) measurements, with both aspects confirmed by using the chiral derivatizing agent (CDA) Mosher's acid chloride {alpha-methoxy-alpha-trifluorophenylacetyl chloride (MTPACI)} to effect enantio-differentiation. The absolute configurations of the dioxane ring using the CDA could only be effected in the case of alnumycin A1, the results of which were in agreement with previous assignments. The dioxane ring conformational mobility and the likely interaction between the MTPA groups coupled with the structural novelty of the diols in the dioxane ring with respect to CDA analysis precluded an absolute configuration assignment for alnumycins A2 and A3 based on empirical comparisons or by computational analysis of through-space NMR shieldings (TSNMRS) emanating from the phenyl groups of the MTPA moieties. (C) 2012 Elsevier Ltd. All rights reserved.
Two new pairs of stereoisomeric alnumycin As, A2 {(2)-(1R,1'RS,4'SR,5'SR)} and A3 {(2)-(1R,1'RS,4'SR,5'RS)}, are described. Similar to alnumycin A1 {(2)-(1R,1'RS,4'RS,5'SR)}, each of these naturally occurring compounds is also a pair of C-1 inverse epimers. The relative configurations of the dioxane ring sidechains were assigned on the basis of H-1 NMR NOE contacts and molecular modeling using density functional theory (DFT) at the M06-2X/6-31G(d) level of theory. The absolute configurations of C-1 and the determination of inverse epimeric relationships were achieved by experimental electronic circular dichroism (ECD) measurements, with both aspects confirmed by using the chiral derivatizing agent (CDA) Mosher's acid chloride {alpha-methoxy-alpha-trifluorophenylacetyl chloride (MTPACI)} to effect enantio-differentiation. The absolute configurations of the dioxane ring using the CDA could only be effected in the case of alnumycin A1, the results of which were in agreement with previous assignments. The dioxane ring conformational mobility and the likely interaction between the MTPA groups coupled with the structural novelty of the diols in the dioxane ring with respect to CDA analysis precluded an absolute configuration assignment for alnumycins A2 and A3 based on empirical comparisons or by computational analysis of through-space NMR shieldings (TSNMRS) emanating from the phenyl groups of the MTPA moieties. (C) 2012 Elsevier Ltd. All rights reserved.
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