Coumarins are associated with a variety of pharmacological activities which have led to the synthesis of numerous derivatives. However, no general method for determination of the absolute configuration of chiral coumarins is known. This has now been achieved for a series of dihydrofuroangelicins bearing a variety of C-8 substituted double bonds, synthesized in the racemic form and resolved through enantioselective chromatography. A combined chemical/chiroptical protocol has been developed in which the C=C double bonds are replaced with a styrenoid chromophore through either (i) cross metathesis, (ii) Heck reaction, or (iii) a combined method of cross metathesis and Heck reaction with about 1 mg sample under mild conditions. The coupling between the styrenoid and coumarin chromophores gives rise to clear-cut exciton coupled CD curves, suitable for assignments of absolute configurations. The solution conformation of the styrenoid derivatives is determined by NMR and DFT molecular modeling; the electronic structure of the 7-hydroxy coumarin chromophore is also clarified by semi-empirical and TDDFT methods. The conformation thus derived, in conjunction with quantitative DeVoe's coupled-oscillator CD calculation, establishes the absolute configurations of the coumarins. The theoretical study described herein justifies the straightforward approach of the current chemical/exciton chirality protocol to this type of dihydrofuroangelicins.

Absolute stereochemistry of dihydrofuroangelicines bearing C-8 substituted double bonds: a combined chemical/exciton chirality protocol

PESCITELLI, GENNARO;DI BARI, LORENZO;
2004

Abstract

Coumarins are associated with a variety of pharmacological activities which have led to the synthesis of numerous derivatives. However, no general method for determination of the absolute configuration of chiral coumarins is known. This has now been achieved for a series of dihydrofuroangelicins bearing a variety of C-8 substituted double bonds, synthesized in the racemic form and resolved through enantioselective chromatography. A combined chemical/chiroptical protocol has been developed in which the C=C double bonds are replaced with a styrenoid chromophore through either (i) cross metathesis, (ii) Heck reaction, or (iii) a combined method of cross metathesis and Heck reaction with about 1 mg sample under mild conditions. The coupling between the styrenoid and coumarin chromophores gives rise to clear-cut exciton coupled CD curves, suitable for assignments of absolute configurations. The solution conformation of the styrenoid derivatives is determined by NMR and DFT molecular modeling; the electronic structure of the 7-hydroxy coumarin chromophore is also clarified by semi-empirical and TDDFT methods. The conformation thus derived, in conjunction with quantitative DeVoe's coupled-oscillator CD calculation, establishes the absolute configurations of the coumarins. The theoretical study described herein justifies the straightforward approach of the current chemical/exciton chirality protocol to this type of dihydrofuroangelicins.
K., Tanaka; Pescitelli, Gennaro; DI BARI, Lorenzo; T. L., Xiao; K., Nakanishi; D. W., Armstrong; N., Berova
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/204463
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