From β‐Amino‐γ‐sultone to Unusual Bicyclic Pyridine and Pyrazine Heterocyclic Systems: Synthesis and Cytostatic and Antiviral Activities

Abstract

Herein we describe the first successful application of the β-amino-γ-sultone system as an intermediate for the synthesis of hitherto virtually unknown 3H-[1,2]-oxathiole [4,3-b]pyridine and pyrazine 1,1-dioxide bicyclic heterocyclic systems. All novel compounds were evaluated for their antiviral and cytostatic activities. Compounds 3 a, 15 a, and 21 a inhibited HIV-1-induced cytopathicity. Compound 7 showed remarkable cytostatic activity, and can be regarded as a potential antitumor candidate for further exploration.

Synthesis of 5‐Amino‐3,3‐dimethyl‐7‐phenyl‐3H‐[1,2]oxathiolo[4,3‐b]pyridine‐6‐carbonitrile 1,1‐Dioxides

“…In fact, the 3H- [1,2]oxathiolo [4,3-b]pyridine 1,1-dioxide (I) (Scheme 1) heterocyclic ring system has been scarcely investigated and documented in the literature. Only very recently, the reaction of 5H-1,2-oxathiol-4-amine, 5-ethyl-5-(phenylmethyl)-, 2,2-dioxide and 5H-1,2-oxathiol-4-amine, 5,5-bis (phenylmethyl)-, 2,2-dioxide with different Michael acceptors such as (E)-3-ethoxy-2-methylacrylaldehyde, (E)-2-phenyl-3-propoxyacryladehyde, b-ketoaldehydes, 2,4-pentanedione, or with a,b-unsaturated aldehydes has afforded a number of heterocyclic derivatives, bearing the 3H- [1,2]oxathiolo [4, 3-b]pyridine 1,1-dioxide moiety, albeit in low to moderate chemical yield [13].…”

“…Very similar 5,5-dialkyl disubstituted 4-amino-5H-1,2-oxathiole 2,2-dioxides, prepared using the same protocol [12], have also been synthesized and transformed into unusual bicyclic pyridine and pyrazine heterocyclic systems showing cytostatic and antiviral activities [13].…”

New Synthesis Method for Sultone Derivatives: Synthesis, Crystal Structure and Biological Evaluation of S-CA

“…In summary, a simple method for the synthesis of the sultone derivative S-CA and its characterization by 1 H-NMR, 13 C-NMR, HMQC and X-ray single crystal diffraction analysis are reported. In addition, S-CA exhibited selective antiangiogenesis on CAM and potent antitumor effect against S180 model.…”

“…The simple and rapid synthesis method we have found has never been reported previously. The newly synthesized compound S-CA was characterized by 1 H-NMR, 13 C-NMR, HMQC and X-ray single crystal diffraction analysis.…”

“…The biological activities of sultones previously included toxicological, skin sensitization, antiviral (anti-HIV and HCMV) and antitumor activities [12][13][14]. Some compounds prepared by total synthesis had antitumor activities due to their sulphonic acid ester structures [15,16].…”