Biological reaction, alcohol ketone alkylation

These two milestone syntheses were soon followed by others, and activity in this field continued to be driven by interest in the biologically active esters of cephalotaxine. In 1986, Hanaoka et al. (27) reported the stereoselective synthesis of ( )-cephalotaxine and its analog, as shown in Scheme 4. The amide acid 52, prepared by condensation of ethyl prolinate with 3,4-dimethoxyphenylacetyl chloride, followed by hydrolysis of the ethyl ester, was cyclized to the pyrrolobenzazepine 53 by treatment with polyphos-phoric acid, followed by selective O-alkylation with 2,3-dichloropropene (54) in the presence of sodium hydride. The resulting enol ether 55 underwent Claisen rearrangement on heating to provide C-allylated compound 56, whose reduction with sodium borohydride yielded the alcohol, which on treatment with 90% sulfuric acid underwent cationic cyclization to give the tetracyclic ketone 57. Presumably, this sequence represents the intramolecular version of the Wichterle reaction. On treatment with boron tribromide, ketone 57 afforded the free catechol, which was reacted with dibromometh-ane and potassium fluoride to give methylenedioxy derivative 58, suited for the final transformations to cephalotaxine. Oxidation of ketone 58... 

Another important feature in the biological action of phosphorus esters is their alkylating property. It is probable that the alkylating ability also plays a direct role in the exertion of the biological action, but it is primarily of importance in the detoxication of the phosphorus ester molecule and in the duration of action. On the basis of theoretical considerations, Melnikov stated in 1961 and it has been widely accepted since then that phosphorus esters alkylate esterases, nitrogen and sulfur compounds of minor importance for the organism, and dealkylate themselves thereby losing their activity (Melnikov, 1972). Several authors studied the dealkylation reaction of phosphorus esters in the presence of amines, amino ketones, amino alcohols, amino acids and other compounds (Shvetsova-Shilovskaya and Lebedeva, 1964 Melnikov et al.. 1965 1967 1968). 

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