Coenzyme Models.48. Novel Diastereo-Differentiating Hydrogen Transfer and “Rope-Skipping” Racemization in Chiral Flavinophanes and 5-Deazaflavinophanes

Seiji Shinkai, Toshiro Yamaguchi, Akito Kawase, Osamu Manabe, Richard M. Kellogg

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Cyclic flavins and 5-deazaflavins with planar chirality [Fl(n) and dFl(n), n = 6, 7, 8, 10, and 12] and their noncyclic analogues [Fl(Bu) and dFl(Bu)] were optically resolved for the first time by a liquid chromatographic method. They did not racemize below 40 °C, but Fl(n) and dFl(n) with a long strap (n ≥ 10) racemized invariably when they were reduced to the 1, 5-dihydro forms. This novel redox-induced “rope-skipping” racemization occurs because the flat (5-deaza)isoalloxazine plane is folded along a line through N(5) [or C(5)] and N(10) like butterfly wings in the reduced forms, and thus, rope-skipping racemization is facilitated. A similar racemization took place via the formation of sulfite adducts at N(5) or C(5), indicating that the adducts also employ the folded conformation. These chiral (5-deaza)flavinophanes could oxidize optically active thiols (62.8% enantiomeric excess) and NADH model compounds (60.0% enantiomeric excess) in an asymmetric manner. When dFl(n) were reduced to dFlred(n), 1H NMR gave a pair of doublets for the two C(5) protons. This indicates that the central ring in the reduced isoalloxazine employs a boat form and that the flip-flop motion is significantly suppressed by the ring structure. By use of the nuclear Overhauser effect, the two 1H NMR peaks were assigned to axial proton (higher magnetic field) and equatorial proton (lower magnetic field). The tracer experiments using dFl(n) established for the first time that the hydrogen transfer to dFl(n) and from dFlred(n) occurs exclusively at the “axial” C(5) position. These novel results were found owing to unique characteristics of cyclic (5-deaza)flavins. Furthermore, the high asymmetric discrimination suggests that planar chirality is a promising approach to the design of new flavoenzyme model systems.

Original languageEnglish
Pages (from-to)4935-4940
Number of pages6
JournalJournal of the American Chemical Society
Volume111
Issue number13
DOIs
Publication statusPublished - Jan 1 1989

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Coenzymes
Flavins
Protons
Hydrogen
Chirality
Magnetic Fields
Nuclear magnetic resonance
Magnetic fields
Butterflies
Sulfites
Ships
Flip flop circuits
Boats
Sulfhydryl Compounds
NAD
Oxidation-Reduction
Conformations
Liquids
Experiments
isoalloxazine

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Coenzyme Models.48. Novel Diastereo-Differentiating Hydrogen Transfer and “Rope-Skipping” Racemization in Chiral Flavinophanes and 5-Deazaflavinophanes. / Shinkai, Seiji; Yamaguchi, Toshiro; Kawase, Akito; Manabe, Osamu; Kellogg, Richard M.

In: Journal of the American Chemical Society, Vol. 111, No. 13, 01.01.1989, p. 4935-4940.

Research output: Contribution to journalArticle

Shinkai, Seiji ; Yamaguchi, Toshiro ; Kawase, Akito ; Manabe, Osamu ; Kellogg, Richard M. / Coenzyme Models.48. Novel Diastereo-Differentiating Hydrogen Transfer and “Rope-Skipping” Racemization in Chiral Flavinophanes and 5-Deazaflavinophanes. In: Journal of the American Chemical Society. 1989 ; Vol. 111, No. 13. pp. 4935-4940.
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abstract = "Cyclic flavins and 5-deazaflavins with planar chirality [Fl(n) and dFl(n), n = 6, 7, 8, 10, and 12] and their noncyclic analogues [Fl(Bu) and dFl(Bu)] were optically resolved for the first time by a liquid chromatographic method. They did not racemize below 40 °C, but Fl(n) and dFl(n) with a long strap (n ≥ 10) racemized invariably when they were reduced to the 1, 5-dihydro forms. This novel redox-induced “rope-skipping” racemization occurs because the flat (5-deaza)isoalloxazine plane is folded along a line through N(5) [or C(5)] and N(10) like butterfly wings in the reduced forms, and thus, rope-skipping racemization is facilitated. A similar racemization took place via the formation of sulfite adducts at N(5) or C(5), indicating that the adducts also employ the folded conformation. These chiral (5-deaza)flavinophanes could oxidize optically active thiols (62.8{\%} enantiomeric excess) and NADH model compounds (60.0{\%} enantiomeric excess) in an asymmetric manner. When dFl(n) were reduced to dFlred(n), 1H NMR gave a pair of doublets for the two C(5) protons. This indicates that the central ring in the reduced isoalloxazine employs a boat form and that the flip-flop motion is significantly suppressed by the ring structure. By use of the nuclear Overhauser effect, the two 1H NMR peaks were assigned to axial proton (higher magnetic field) and equatorial proton (lower magnetic field). The tracer experiments using dFl(n) established for the first time that the hydrogen transfer to dFl(n) and from dFlred(n) occurs exclusively at the “axial” C(5) position. These novel results were found owing to unique characteristics of cyclic (5-deaza)flavins. Furthermore, the high asymmetric discrimination suggests that planar chirality is a promising approach to the design of new flavoenzyme model systems.",
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