Selective saponification

A substituted benzoic acid serves as precursor for the nontricyclic antidepressant bipena-mol (175). Selective. saponification of ester 171 afford.s the half-acid 172. Reaction of the acid chloride derived from this intermediate (173) with ammonia gives the amide 174. Reduction of the last by means of lithium aluminum hydride gives bipenamol (175) [44]. 

Saturation of the aromatic ring of pentopril analogues is also consistent with ACE inhibition as demonstrated by the oral activity of indolapril (23). The necessary heterocyclic component (21) can in principle be prepared by catalytic perhydrogenation (Rh/C, HOAc) of the corresponding indole. A single isomer predominates. The product is condensed by amide bond formation with the appropriate alanylhomophenylalanyl dipeptide ester 20 to give 22. Selective saponification to 23 could be accomplished by treatment with HCl gas. Use of the appropriate stereoisomers (prepared by resolution processes) produces chiral indolapril [8]. 

Chiral multiple-coupling reagents have been prepared in enantiomerically pure form by enantio-selective saponification of diesters of meso-2-nitrocyclohexane-l,3-diols (Eq. 3.44) with pig liver esterase (PLE).69... 

For this purpose, nitronate (107) containing the EtSCO- fragment was synthesized followed by selective saponification of this fragment with mercury acetate in water, which occurred with retention of the nitronate structure. 

Thus, to confirm the location of the two hydroxyl groups in inumakilactone A (28), this compound was selectively acetylated, and its diacetate selectively saponificated. The thus obtained 15- and 3-monoacetates were oxidized to the corresponding ketones with Jones reagent (Scheme 3) [40],... 

Fig. 18 Schematic illustration of the preparation and photoresponsive behavior of the polypeptide XXIII, consisting oftwo amphiphilic helical rods linked by an azobenzene unit, a) Selective saponification of COOCH3 side...

Dimethyl-4-carbethoxy-2-cyclohexen-l-one and 3,5-di-methyl-2-cyclohexen-l-one have always been prepared from acetaldehyde and acetoacetic ester through the Knoevenagel condensation.2 The keto ester has previously been obtained by selective saponification and decarboxylation methods which have involved heating the crude condensation product with water at 140° 2 3 or with sodium ethoxide in alcohol.3 The ketone has been obtained from the same condensation product by prolonged refluxing in 20% sulfuric acid.2-4 6... 

Dihydrofulvalene (368) has been reported to enter into Domino Diels-Alder cycloaddition with dimethyl acetylenedicarboxylate to give an ca 1 1 mixture of the polycondensed diesters 502 and 503 (Scheme 74).352,354,417 These products can be most readdy separated by selective saponification of the less hindered isomer. Both molecules contain the fundamental a//-c/s-tetracyclo[7.2.1.04 11.06, l0]do-decane nucleus but with an additional bond across the central portion. In 502, this linkage can be cleaved by a number of methods to produce appreciably more func-... 

Intermediate 4-nitrobenzyl ester protection has been used in the efficient syntheses of A -Z-protected aminodicarboxylic acid co-tert-butyl estersP via terf-butylation of Z-Asp-ONbz followed by selective saponification of Z-Asp(OtBu)-ONbz.P ... 

Like the 2-nitrobenzyl ester, the 4,5-dimethoxy-2-nitrobenzyl ester has attracted attention as a photolabile caging group. It has also been used for side-chain carboxy protection in the synthesis of misacylated transfer RNAs.P l In this case, both the a- and side-chain carboxyls were first protected a selective saponification of the a-ester afforded the side-chain protected material. 

Any of the carboxy protecting groups discussed above are applicable to the side-chain protection of aspartic and glutamic acids. A procedure for the preparation of a di(4,5-dimethoxy-2-nitrobenzyl) aspartate was given in Section 2.4.2.I.2. Selective saponification with LiOH leads to the side-chain protected product.P l... 

Scheme 16 Alcalase-Mediated Selective Saponification of Methyl Esters in the Presence of the Base-Labile Fmoc Groupl " ...

Scheme 20 Lipase-Assisted Selective Saponification of C-Terminal (Hep), 2-Bromoethyl, and 2-(A-Morpho-lino)ethyl EstersP ...

Scheme 24 Enzymatic Selective Saponification of the C-Terminal Heptyl Esters in the Synthesis of Phospho-...

Optically pure (+)-6a (MGS0008) (64% yield) and its enantiomer (-)-6b (73% yield) were produced by acidic hydrolysis of carboxylic acids (+)-19 and (-)-19, respectively. Compounds (+)-19 and (-)-19 were obtained through selective saponification of the ester moiety of (+)-18 under basic conditions (93% yield), followed by optical resolution of the resulting (+)-19 with (R)- and (S)-l-phenylethylamine [(+)-19 39% yield, (—)-19 36% yield], respectively (see Scheme 3.1). 

Selective saponification leading to hydroxy-telechelic oligomethacrylates. 

The (S)-serine derived methyl ( R)-2- erJ-butyl-2,3-dihydrooxazole-3-carboxylate reacts with ethyl diazoacetate under bis(2,4-pentanedionato)copper catalysis to afford the expected bi-cyclic product in good yield54, but in this case the inducing power exhibited by the bulky 2-tm-butyl group is rather weak (diastereofacial selectivity 70 30). However, the major diastereomer can be easily separated by chromatography and selective saponification to give the enantiomerically pure cyclopropanecarboxylic acid. 

The separation of diastereomeric cyclohexanols on a preparative scale is often tedious. Sometimes the diastereomers are barely resolved by GC, or recourse to HPLC must be taken. Thus, the separation of the above cis- and /ran.s-alcohols on a preparative scale is of practical interest. Treatment of the mixture of the alcohols with chloroacetyl chloride, followed by two fractional crystallizations, gives the Pwi.v-acetate selectively. Saponification affords the diastereo- and enantiomerically pure /rrm-alcohol on a 10-g scale12. 

Stille macrocyclization. Several macrocylic antibiotics contain a y-oxo-a, y3-unsaturated ester group. Macrolides of this type can be obtained by Stille intramolecular coupling.1 The substrates are available from Mitsunobu esterification of propriolic acid with an w-hydroxy ester followed by hydrostannylation to give /3-stannyl alkcnoates I as a 1 1 mixture of (Z)- and (E)-isomcrs. Selective saponification of the methyl ester... 

Acetylation of saccharide hydrazones (65) with acetic anhydride in pyridine affords per-O-acetylatcd derivatives (such as 66) with acyclic hydrazones and A-acetyl-O-acetyl derivatives with the cyclic ones. 5 "4 t 4,i63 jn [1C as, casC [lc [sjpi group attached to the aryl moiety is not acetylated, but the more basic NH group attached to the sugar moiety is acetylated. The 0-acetyl groups are split off by base more readily than the iV-acctyl groups.218 and methods for selective saponification have been devised. With acetyl chloride in A/, A-tli methyl aniline, the NH group attached to the aryl residue becomes acylated and acyclic hexose hydrazones give A-acetyl-penta-O-acctyl derivatives (64) 165 similarly, benzoylation with benzoyl chloride in pyridine affords W-benzoyl-0-bcnzoyl deri vatives (Scheme 15)219... 

Gabriel synthesis. Following Al-alkylation of the oxamide, selective saponification removes the ethyl ester to afford RNHCOOBn. The N-Boc derivative is similarly transformed. 

Selective saponification.". An es t-BuOK in wet THF at 0° without aff methine hydrogen. 

Selective saponification. An ester group can be selectively hydrolyzed with r-BuOK in wet THE at 0° without affecting a malonate unit having at least one active methine hydrogen. 

By selective saponification of carboalkoxyl groups in the a- and other positions of the quinuclidine molecule it was possible to obtain for example a monoester (XX), e.g. by treatment of the diethylester of 3-carboxymethyl-quinuclidine-2-carboxylic acid (XIX) with water at room temperature. The same method was used in the S3mthesis of compounds containing other functional groups in positions 2 and 3 [95]. 

The synthesis of BAZ was continued by hydrogenating 105 and protecting the amino groups with BOC to give 109. The differentiation of the ester groups is possible by a selective saponification of the methyl ester to acid 110 which is converted into the amide 111 (Fig. 42). 

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