S. P. Bondarenko

Antineoplastic Isoflavonoids Derived from Intermediate ortho-Quinone Methides Generated from Mannich Bases.

The regioselective condensations of various 7‐hydroxyisoflavonoids with bis(N,N‐dimethylamino)methane in a Mannich reaction provided C‐8 N,N‐dimethylaminomethyl‐substituted isoflavonoids in good yield. Similar condensations of 7‐hydroxy‐8‐methylisoflavonoids led to the C‐6‐substituted analogs. Thermal eliminations of dimethylamine from these C‐6 or C‐8 N,N‐dimethylaminomethyl‐substituted isoflavonoids generated ortho‐quinone methide intermediates within isoflavonoid frameworks for the first time. Despite other potential competing outcomes, these ortho‐quinone methide intermediates trapped dienophiles including 2,3‐dihydrofuran, 3,4‐dihydro‐2H‐pyran, 3‐(N,N‐dimethylamino)‐5,5‐dimethyl‐2‐cyclohexen‐1‐one, 1‐morpholinocyclopentene, and 1‐morpholinocyclohexene to give various inverse electron‐demand Diels–Alder adducts. Several adducts derived from 8‐N,N‐dimethylaminomethyl‐substituted isoflavonoids displayed good activity in the 1–10 μm concentration range in an in vitro proliferation assay using the PC‐3 prostate cancer cell line.

Synthesis of Formononetin Analogs

Derivatives of the natural isoflavone formononetin were synthesized. Acylation and alkylation of the phenolic hydroxyls and the chromone ring were investigated.

Synthesis of analogs of natural isoflavonoids containing phloroglucinol

Analogs of the natural isoflavonoids biochanin A and orobol were synthesized. Alkylation involving phenolic hydroxyls and the chromone ring was studied.

Synthesis of cytisine derivatives of flavonoids. 2. Aminomethylation of 7-hydroxyisoflavones

Aminomethylation of natural 7-hydroxyisoflavones and their analogs by the alkaloid (−)cytisine was studied. Substituted 8-(cytisin-12-yl)methyl-7-hydroxyisoflavones were synthesized.

Reaction of natural isoflavonoids and their analogs with hydroxylamine

Recyclization of the chromone ring in several natural isoflavonoids and their analogs by reaction with hydroxylamine was studied. It has been found that the most suitable base for carrying out the reaction is N-methylmorpholine. Several derivatives of 4-aryl-5-(2-hydroxyphenyl)isoxazole were synthesized.

Synthesis and aminomethylation of 7-hydroxy-5-methoxyisoflavones

A synthetic method for 7-hydroxy-5-methoxyisoflavones starting from 5,7-dihydroxyisoflavones was developed. Dimethylcarbamoylchloride was proposed for protection of the 7-hydroxy group. Aminomethylation of the synthesized 7-hydroxy-5-methoxyisoflavones by formaldehyde aminals was studied.

Synthesis of cytisine derivatives of coumarins

New substituted 4-chloromethylcoumarins that were used as alkylating agents to modify cytisine were synthesized by Pechmann condensation. A series of 4-(12-cytisylmethyl)coumarins containing pharmacophores of the natural heterocycles coumarin and cytisine in a single molecule was prepared. The alkylation gave the best results if diisopropylethylamine was used as the base.

Synthesis of amino-acid derivatives of formononetin and cladrin

Aminomethylation of natural isoflavones by amino acids was studied. Conditions for selective production of N-(4H-4-oxochromen-8-yl)methyl-substituted amino acids were found.

Chemistry of 3-hetarylcoumarins 3*. Synthesis and aminomethylation of 7′-hydroxy-3,4′- bicoumarins

An improved procedure for the synthesis of 7′-hydroxy-3,4′-bicoumarins has been developed. Their 8′-aminomethyl derivatives were obtained by interaction with aminals.

Synthesis of flavonoid derivatives of cytisine. 1. aminomethylation of 7-hydroxy-3-arylcoumarins

Aminomethylation involving the natural alkaloid (–)-cytisine of analogs of natural 3-arylbenzopyran-2ones was studied. Substituted 8-(cytisin-12-yl)methyl-3-aryl-7-hydroxycoumarins were synthesized.