Study on the synthesis of phosphonate-containing bioactive compounds and valuable olefination precursors

Abstract

4-Oxo-2-alkenylphosphonate have been synthesized from phosphonoalkyl-2-isoxzolines via their eliminative ring opening by treatment with LDA and subsequent hydrolysis with titanium(III) chloride. The overall synthetic procedure presents a new method for regioselective g-acylation of allylic phosphonate presents a new method for regioselective g-acylation of allylic phosphonates. The potential of 4-oxo-2-alkenylphosphonates as useful building blocks for synthesis of polyethylene-structured natural compounds has been verified by their olefination with aldehyde, affording dienones. Also 4-oxo-2-alkenylphosphonates have been synthesized via aliphatic Friedel-Crafts acylation of allyl- and vinylsilanes and base-promoted double bond migration in excellent yields. The silylated allylic phosphonates as intermediates were obtained from vinylic phosphonates as well as allylic phosphonates. In addition, the regioselective Friedel-Crafts acylations of allylic or vinylic silane were successfully used for 4-oxo-2-alkenylsulphones which are regarded as another olefination precursors for polyethylenic chain. The γ -silylated allylic phosphonates were also successfully applied to dienenyl silanes and α -alkylated β -carboxylic acid phosphonates. The treatment of allylphosphonates with LiHMDS, followed by successive addition of chlorotirmethylsilane and carbonyl reagent, afforded various substituted dienylsilanes. α -alkylated β -carboxylic acid phosphonates were synthesized by ozonolysis and oxidative treatment of α -alkylation of γ -silylated allylic phosphonates and these compounds were transformed to diethyl phosphonoester, amide, and thioester, through acid chloride as an intermediate. In the synthesis of bioactive phosphonates compounds, carbohydrates analogues such as 1,2-oxaphospholene 2-oxides and 1,2-oxaphospholane 2-oxides, and sarkomycin analogues which have been regarded as important antitumor agents, were synthesized. The phosphorylated sarkomycin analogues were...