Pyruvyl chloride

Sometimes the addition of a small amount of ZnCh as a catalyst is recommended, e.g. succinic acid is transformed to the dichloride only in the presence of this catalyst. It has to be noticed, however, that under these conditions hydrogen chloride is evolved and, therefore, acid sensitive compounds cannot be taken. Af-acylamino acid chlorides and chlorides of fully acetylated sugar acids are also obtainable in yields of 70% or more. Whereas most reagents seem to be unsuited to the preparation of acid halides of a-keto acids, dichloromethyl methyl ether is successful in this reaction (equation 10). Pyruvyl chloride can now be made in ca. 50% yield. In some examples the corresponding a,a-dibromomethyl methyl ether has also been tested. ... 

Two new cephalotaxine esters having significant antileukemic activity, neoharringtonine (11) and anhydroharringtonine (12), were isolated in 1992 by Wang and co-workers (9) from C. fortunei Hook f. These authors also reported their semisynthesis from cephalotaxine and harringtonine, respectively (Scheme 31). On treatment with phenyl pyruvyl chloride in the presence of pyridine, cephalotaxine (1) produced an intermediate a-keto ester. Reformatsky reaction of this cephalotaxyl phenyl pyruvate with methyl bromoacetate yielded a mixture of neoharringtonine (11) and its epimer. 

Based on a multi-component condensation approach related to the Doebner reaction,Gopalsamy et developed a solid-phase synthesis for this clinically useful pharmacophore. Thus, starting from Rink resin 65, acylation with the required N-Fmoc-amino acid 232 and deprotection with piperidine gave the polymer-supported amine 233 (90% yield) which was acylated with pyruvyl chloride (234). Immobilised pymvic amide 235 was refluxed with excess of preformed benzyUdene aniline 239 or alternatively condensed with an excess of an equimolecular mixture of aldehyde 236 and anilines 237. Cleavage of 238 with 45% TFA afforded compounds 240 in good yields and with high purities (>90%) (Scheme 4.3.5). 

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