Novel N -quinonyl amino acids and their transformation to 3-substituted p -isoxazinones

Abstract

Quinonyl amino acids are building blocks in the preparation of peptides which target the quinonic drug to cancer damaged area. Novel N-(3-chloro-1,4-dihydro-1,4-dioxonaphthalen-2-yl)-alpha-amino acids la-f were prepared by direct substitution of 2,3-dichloro-1,4-naphthoquinone. The quinonic moiety was reduced by NaBH4 to yield the corresponding hydroquinones 2a-f, which in acidic conditions underwent internal cyclization to yield the 3,4-dihydro-2H-naphth[1,2-b]-1,4-oxazine-2-ones (six-membered azlactones) 3a-f.

Synthesis of Amino Acid–Naphthoquinones and In Vitro Studies on Cervical and Breast Cell Lines

“…In several investigations, the generation of compounds 3a , 3b , 3d , 4a , and 4d has been reported [19,20,21,22,23,24,25,26,27,28,29], and their boiling point, infrared, and 1 H NMR spectra have been determined. Compounds 4b , 4c have been reported and used as intermediates for secondary reactions or biological evaluations, but we did not find their complete characterization [33,34], while 3c , 3e , and 4e have not been previously reported and, therefore, their complete characterization was carried out.…”

“…m. p.: 175–177 °C; IR (ATR): 3303, 1743, 1676, 1600, 1555, 1406, 1294, 1262, 1226, 700 cm −1 ; 1 H NMR (300 MHz, DMSO- d 6 ) δ: 7.94 (dd, J = 9.0/2.9 Hz, 2H), 7.81 (td, J = 7.5/1.5 Hz, 1H), 7.73 (td, J = 7.5/1.5 Hz, 1H), 7.29–7.15 (m, 5H), 6.68 (d, J = 4.3 Hz, 1H), 5.32 (q, J = 6.2 Hz, 1H), 3.25 (dd, J = 5.7/2.8 Hz, 2H) ppm. (Characterization according to literature [22,29]. )…”

“…In this regard, the synthesis and biological activities of some naphthoquinone–amino acids have been reported in several publications; nonetheless, all of these methodologies present different drawbacks, like low yields and/or long reaction times [19,20,21,22,23,24,25,26,27,28,29]. To our knowledge, the synthesis of naphthoquinone–amino acid derivatives has not been reported using microwave and ultrasound irradiation, which offer diverse advantages to conventional synthesis.…”

Synthesis, electrochemical and spectral properties of some ω-N-quinonyl amino acids

“…In view of the potential clinical significance of cytotoxic quinone-bearing peptides, it became very important to increase the arsenal of related natural and unnatural quinonyl amino acids and study their chemical, spectral and electrochemical properties (Gorohovsky and Bittner, 2001). In this paper we describe the preparation of a large variety of quinonyl amino acids via the 1,4-Michael-like addition and present some of their spectroscopic and electrochemical properties.…”

Direct Nitration of 3-Arylamino-2-chloro-1,4-naphthoquinones

“…In the course of our work on anticancer quinones, 12,13 we had to prepare and to test both the mononitro-and dinitrophenyl derivatives of naphthoquinone. As the classical route to such compounds was unfeasible, we developed an alternative two-step synthesis of such compounds.…”