Synthesis and properties of deoxypegan-1-one

Abstract

547.856.1+547.75Quinazolyl-2-propionic acid hydrochloride (5) was synthesized by reduction of N-(o-nitrobenzyl)succinimide with tin chloride. A pyrroloquinazolin-1-one {4, 3,9-dihydropyrrolo[2,1-b]quinazolin-1(2H)-one} was prepared in 68% yield by heating 5 in Ac 2 O and subsequent treatment with Et 3 N. Compound 4 was obtained in 71% yield in one step by reduction of N-(o-nitrobenzyl)succinimide with Fe in the presence of HCl. Compound 4 was protonated, alkylated, and acylated on the N (4) atom. Derivatives of quinazolyl-2-propionic acid and 1-(2-aminobenzyl)succinimide were prepared by reaction of derivatives of 4 with nucleophilic reagents.Key words: alkylation, acylation, 3,9-dihydropyrrolo[2,1-b]quinazolin-1(2H)-one, quinazolyl-2-propionic acid, 1-(2-aminobenzyl)succinimide.The search for new synthetic pathways and the study of the properties of pyrrolo[2,1-b]quinazoline derivatives have recently acquired increasing importance. 1,2,3,9-Tetrahydro-and 9-oxo-dihydro derivatives of this heterocyclic system [peganine (1a), deoxypeganine (1b), vasicinone (2a), and deoxyvasicinone (2b)] are the principal alkaloids of Peganum harmala and P. nigellastrum and possess distinct cholinotropic activity [1,2]. For this reason, they have been used pharmacologically to treat various types of dependency (nicotine, alcohol, drug) and the depressive states, Alheizmer disease, and respiratory malfunctions associated with them [3][4][5][6][7].Other derivatives of pyrrolo[2,1-b]quinazoline are also known. These include 2,3-dihydropyrrolo[2,1-b]quinazolin-1,9-dione (3) [8-11] and 3,9-dihydropyrrolo[2,1-b]quinazolin-1(2H)-one (deoxypegan-1-one, 4), which was prepared for the first time by Gabriel at the beginning of the last century [12]. However, the properties of 3 and 4 have practically not been studied because of their scarcity. Currently known chemical transformations of 4 include only reduction [12][13][14][15] and opening of the pyrrole ring upon reaction with nucleophiles [12][13][14]. The only reactions with electrophiles are formation of the protonated salts 4·HI and 4·H 2 SnCl 6 [12] and the picrate [14].