I. TOTAL SYNTHESIS OF CORYDALIC ACID METHYL ESTER AND PREPARATION OF SOME HYPOTHETICAL INTERMEDIATES IN THE BIOSYNTHESIS OF BENZO(C)PHENANTHRIDINES. II. STUDY OF THE REACTION BETWEEN HEXAFLUOROBIACETYL AND AROMATIC ORTHO DIAMINES AND OF THE STABILIZATION OF NEUTRAL COVALENT HYDRATES BY TRIFLUOROMETHYL GROUPS DURING THE PREPARATION OF RIBOFLAVIN SYNTHASE INHIBITORS (3-ARYLISOQUINOLINES, CARBINOLAMMONIUM, TRIFLUOROPYRUVALDEHYDE)

WAI-CHEONG WONG, Purdue University

Abstract

Part I. The first total synthesis of corydalic acid methyl ester (22) was achieved using anhydride 39 and Schiff base 40 as the key synthons. Anhydride 39 was prepared from either piperonal (41) or 3-ethoxysalicylaldehyde. During the preparation of 40, a novel method of synthesizing 3-aminoisoquinolines was discovered. The reaction between 39 and 40 gave a mixture of diastereomeric 52 and 53. Subsequent decarboxylation afforded a mixture from which trans 54 was isolated. Lactam 54 was then converted to corydalic acid methyl ester in two steps via ester 56. This approach to 3-arylisoquinolines was modified to prepare hypothetical biosynthetic intermediate 65. Thus, 22 was reduced to aldehyde 59 which was then isolated as acetal 63. Subsequent hydrolysis with HCl/THF afforded carbinolammonium chloride 65. Although enaminoaldehyde 2 could not be obtained, compound 76 with a novel bicyclic structure was identified. In addition, an aryl migration was observed during the pyrolysis of acetates 79 and 82. Part II. In preparation for the synthesis of riboflavin synthase inhibitors, the reaction between hexafluorobiacetyl (19) and aromatic ortho diamines was studied. Thus, a number of trifluoromethylated pyrazine-containing heterocycles resulted. Moreover, neutral covalent hydrates 48-51 were isolated, as a consequence of the stabilization by trifluoromethyl groups, and fully characterized. Also investigated was the reaction between trifluoropyruvaldehyde and aromatic ortho diamines.

Degree

Ph.D.

Subject Area

Organic chemistry

COinS