Phthalyl protective group

The BOP- or PyBOP-mediated SPPS of phosphinot or phosphono peptides can be carried out without protecting the phosphinic or phosphonic acid group. Indeed, phosphinic acids are activated, but the P—N bond is not formed. Phosphonic acids are also acti-vatedt and in fact an amide of methyl phenylphosphonic acid has been obtained, however, in the case of protected a-amino phosphonic acids, phosphonamides are only obtained by using AT-phthalyl protection. Side-chain unprotected phosphorylated tyrosine [Tyr(P03H2)] can be coupled by solid-phase synthesis using BOP (PyBOP), but pyrophosphate formation is also observed and some particular Tyr(P)-peptide syntheses are prone to total failure. ... 

Phthalyl alcohol, HOCH2CeH4CH20H-o. Mol. wt. 138.16, m.p. 64°. Prepared by reduction of phthalic anhydride with lithium aluminum hydride in ether (87% yield). In a novel and efficient synthesis of cyclopropanone hydrate, Grewe and Struve used the o-xylylene acetal protective group (1) and, after elimination of... 

Diphenylmethyl esters of A-protected [a-amino(alkyl)]phosphonic acids, conveniently obtainable from the acid and diphenyldiazomethane, may be hydrogenolysed without loss of A-protecting group (benzyloxycarbonyl, t-butoxycarbonyl, or phthalyl). ... 

A mixture of bromacetaldehyde diethyl acetal and phthalyl alcohol containing a little p-toluenesulfonic acid heated slowly in an oil bath with distillation of the resulting ethanol during- ca. 45 min., finally under reduced pressure bromacetaldehyde o-xylylene acetal. Y S0%,—The protective group can be removed by catalytic hydrogenolysis. R. Grewe and A. Struve, B. 96, 2819 (1963). 

The phthalimido group has always been an attractive alternative to amine protection in chemical synthesis. Native phthalyl amidase was isolated from Xanthiobacter agilis and subsequently cloned and overexpressed in Streptomyces lividans. Phthalyl amidase selectively deprotects phthalimido groups under very mild conditions (30°C in 200 mM potassium phosphate buffer, pH 8.0) in a one-pot reaction to produce phthalic acid and the free amine. The enzyme has been shown to deprotect several primary amines of distinctly different structures [19]. 

---