Research On Efficient Chiral ~1h Nmr Analysis Of Indoloquinazoline Alkaloids With A Chiral Phosphoric Acid

Indoloquinazoline alkaloids represents one type of important natural products with anti-inflammation, antibacterial and anticancer activities,thus becoming attractive synthetic targets. Resently, our group developed efficient catalytic asymmetric transformations for the synthesis of indoloquinazoline alkaloids Phaitanthrins A, Cephalanthrin-A and their derivatives. However, one- or two-step derivation of these indoloquinazoline alkaloids has to be done before each chiral HPLC analysis because of their high polarity and/or poor solubility. Thus, the development of fast and efficient analytic method for the determination of enantioselectivity of indoloquinazoline alkaloids and their derivatives is of great importance. In this thesis, A chiral phosphoric acid promoted enantioselective NMR recognition and determination of indoloquinazoline alkaloids phaitanthrins A, cephalanthrin-A and their derivatives was described, which conveniently gives their optical purities with high accuracy. Importantly, this methodology was further employed in the direct analysis of reaction mixtures of amino acid metal salts catalyzed asymmetric synthesis of phaitanthrins A, providing access to the optimized reaction conditions in high efficiency.First, a variety of chiral phosphoric acids were synthesized with several steps according to the literatures;Second, we synthesized Cephalanthrin-A and their derivatives by the addition-decarboxylativation reaction between malonic acid and Tryptanthrin in the promotion of chiral Nickel catalyst; we also synthesized phaitanthrins A with the promotion of amino acid salt.With the sensor and guests in hand, we developed a chiral phosphoric acid promoted NMR recognition and determination of various indoloquinazoline alkaloids type tertiary alcohols, providing a rapid access to the optical purities of the tertiary alcohols with high accuracy.Importantly, the application of this methodology in the fast evaluation of reaction conditions in catalytic asymmetric transformations enhances the importance of this chiral NMR analysis method. In accounting for the obtained good chiral recognition and determination results, a possible recognition mode was also proposed.