Masked carboxyl group

Transformation of chiral nitrones into enantiomer enriched a-chiral N -hydroxylamines and their derivatives, has been successfully employed in the enantioselective synthesis of (+ )-(R)- and (—)-(S)-zileuton (216). An expeditious synthesis of thymine polyoxin C (347), based on the stereocontrolled addition of 2-lithiofuran (a masked carboxylate group) to the A-benzyl nitrone derived from methyl 2,3-O-isopropylidene-dialdo-D-ribofuranoside, is described (Scheme 2.151) (194). 

Trimethylsilyl-l,3-dithianes can also serve as masked carboxyl groups. The principle is exemplified by the transformations shown in Scheme 2.124 that form part of a synthesis of the [Uactam antibiotic Thienamycin.252... 

The oxazoline moiety is a masked carboxyl group. A chiral oxazoline moiety attached to enamine 230 confers chirality to the double bond on reduction. Separation of the dia-stereomers followed by hydrolysis of the oxazoline moiety provide 3-amino-4,4-difluoro-or 3-amino-4,4,4-trifluorobutanoates 233 in enantiomerically pure forms (see Scheme 9.51) [79]. 

In readily available (see p. 22f.) cyclic imidoesters (e.g. 2-oxazolines) the ot-carbon atom, is metallated by LDA or butyllithium. The heterocycle may be regarded as a masked formyl or carboxyl group (see p. 22f.), and the alkyl substituent represents the carbon chain. The lithium ion is mainly localized on the nitrogen. Suitable chiral oxazolines form chiral chelates with the lithium ion, which are stable at —78°C (A.I. Meyers, 1976 see p. 22f.). 

If only the O-H, as opposed to the carbonyl, of a carboxyl group has to be masked, it can be readily accomplished by esterification. Alkaline hydrolysis is the usual way for regenerating the acid. t-Butyl esters, which are readily cleaved by acid, can be used if alkaline conditions must be avoided. 2,2,2-Trichloroethyl esters, which can be reductively cleaved with zinc, are another possibility.267 Some esters can be cleaved by treatment with anhydrous TBAF. These reactions proceed best for esters of relatively acidic alcohols, such as 4-nitrobenzyl, 2,2,2-trichloroethyl, and cyanoethyl.268... 

The first conversion of protoberberines to phthalideisoquinoline alkaloids was achieved by Moniot and Shamma (88,89). 8-Methoxyberberinephenol-betaine (131), derived from berberine (15) (Section III,B,2), is an attractive compound having a carboxyl group masked as an imino ether in ring B. The masking was uncovered by hydration with water-saturated ether to furnish dehydronorhydrastine methyl ester (367) (Scheme 65). On N-methylation (68%) and subsequent sodium borohydride reduction (90%), 367 provided (+ )-/ -hydrastine (368) and ( )-a-hydrastine (369) in a 2 1 ratio. Compound 367 was converted to dehydrohydrastine (370), which also afforded 368 and 369 by catalytic hydrogenation. 

Maleic acid is a linear four carbon molecule with carboxylate groups on both ends and a double bond between the central carbon atoms. The anhydride of maleic acid is a cyclic molecule containing five atoms. Although the reactivity of maleic anhydride is similar to other cyclic anhydrides, the products of maleylation are much more unstable toward hydrolysis, and the site of unsaturation lends itself to additional side reactions. Acylation products of amino groups with maleic anhydride are stable at neutral pH and above, but they readily hydrolyze at acid pH values around pH 3.5 (Butler et al., 1967). Maleylation of sulfhydryls and the phe-nolate of tyrosine are even more sensitive to hydrolysis. Thus, maleic anhydride is an excellent reversible blocker of amino groups to temporarily mask them from reactivity while another... 

Figure 18 UV photopatterning method. The molecular structure of a photocleavable SAM formed on glass surfaces. UV irradiation through masks placed on top of SAM-modified microchannels leads to the production of hydrophilic carboxylate groups in the irradiated regions (Zhao et al, 2001).

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