Phthaloyl derivatives

The photochemical cyclization of anthranilonitriles (190 Section 4.04.2.1.2) yields indazoles (72CC126). Reduction of o-benzonitrile with lithium aluminum hydride yields indazole (75ACS(B)1089). 2-Aminoindazole (576) has been prepared in 94% yield from (574) via the o-phthaloyl derivative (575 = o-phthaloyl) (72JOC2351). Similarly, treatment... 

As already observed for azidoglucose-derived donors, glycosylations with azidolactose-derived donors (21f-a-21j-a, Table XXIV) also exhibited high reactivity and/ selectivity (92,114,115,154,161,162). With these results in hand, excellent preconditions for successful syntheses of the Le and Ley antigens have been presented (164,165). Representative examples for the decisive glycoside-bond formations are compiled in Table XXV. Comparison of the results of V-phthaloyl protection and of the azido group does not exhibit advantages for the use of TV-phthaloyl derivatives. 

As shown by Sato et al. N-phthaloyl derivatives of C-unprotected amino acids efficiently undergo decarboxylation upon irradiation [248,249]. In this case, the iV-phthaloyl a-amino acid of methionine 310 represents an exception, because the normal decarboxylation route is not followed. Two main products are obtained, the trans-hydroxy acid 313 and the tetracyclic lactone 314 [250, 251]... 

The statine-like moiety in one of the first drugs, saquinovir (23-8), comprises a transition state mimic for the cleavage of phenylalanylprolyl and tyrosylprolyl sequences. Constmction starts with the protection of the amino group of phenylalanine as its phthaloyl derivative (Phth) by reaction with phthalic anhydride this is then converted to acid chloride. The chain is then extended by one carbon using a Friedel-Crafts-like reaction. The required reagent (21-2) is prepared by reaction of the enolate obtained from the /7A-silyl ether (21-3) of glyoxylic acid and lithio... 

Many amino adds condense with phthalic anhydride at 180-185 °C to yield crystalline phthaloyl derivatives (AT-substituted phthalimides). 

S)-2-Aminopropyl benzyl ether, polymer-supported reagent. The polymer is prepared by reaction of the N-phthaloyl derivative of (S)-2-aminopropanol with the Merrifield polymer in the presence of KH and 18-crown-6 in THF/HMPT followed by hydrazinolysis. 

L-Cysteine was transformed into optically active a-alanine derivative as S-benzyl-A-phthaloyl derivative by desulfurization with Raney Ni (eq. 13.75).152... 

Some sulfated galactans, or products of their partial depolymerization, exhibit antioxidant activity.684,685 The chemistry of radical scavenging effects is not very clear, especially taking into account the fact that several products of chemical modifications of natural polysaccharides, such as oversulfated, phosphorylated, acety-lated and phthaloylated derivatives, may demonstrate stronger antioxidant activity than the raw material.685-688... 

N-Phthaloyl derivatives of a-amino acids and alcohols can be obtained without racem-ization by reaction with 1 in THF (addition of triethylamine can be helpful). The HjNCOOCjH, also formed can be removed by evaporation under reduced pressure. Yields are generally 70-80%."... 

Within A -Phth-protected amino acid derivatives the C—N bond is extremely susceptible to basic and nucleophilic conditions, thus, leading to unwanted base-catalyzed side reactions of the Phth derivatives in the course of synthetic steps. The applicability of the phthalimido chemistry has been extended by converting the phthalimido moiety into the corresponding 2-(pyrrolidinocarbonyl)benzamide derivative 81, thereby eliminating the base- and nucleophile-sensitivity of the parent phthaloyl derivative (Scheme... 

In peptide chemistry, in addition to the initially used acid chloride methodb h A -Phth amino acids can be coupled by the entire repertoire of coupling methods, i.e. mixed anhydrides, symmetrical anhydride, active ester, and the azide method.W Due to the add stability of A -phthaloyl derivatives, the acid hydrolyses of esters are readily performed.b h... 

The yields range from 50 to 07% and appear to pees through a maximum whioh is a function of the reaction time. The benzyl ohloridu formed combines iritli the benzene used as a solvent. The use of I molar equivalent aluminum chloride per mt ar equivalent of add chloride reeulto in the formation of a polythkwster whioh in the oaae of the if-phthaloyl derivative" bae a molecular v ight of about IfiOO (m.p. 256-2BO ). 

Overall, the SAR data for the linker between N-4 and the imide group show that this region does not provide any interactions with the receptor and merely acts as a spacer. Some studies point to a role for this region in the modulation of the intrinsic activity of the arylpiperazines and of their selectivity for the 5HT-1A receptor. The general observation is that potency is optimized with a four carbon linker and drops off significantly as the chain is shortened, as exemplified by the phthaloyl derivatives (99) (434). This preference is fur-... 

The reagent is used for conversion of an amino acid into its phthaloyl derivative without racemization. The acid, the reagent, and triethylamine are heated in phenol... 

Water has also been judiciously added as a cosolvent to increase reaction rates. In the dehydrobromination of 32 (Figure 4.18), using 6% water as cosolvent was found to give the highest yield of the 1,4-diene 33 and the lowest yield of the undesired 4,6-diene 34 [54]. Water increases the solubility of the base in this reaction. For the deprotection of N-phthaloyl derivatives by NaBH4 (Figure... 

Riptide synthesis [1, 359, after citation of ref. 14]. When phthalic acid is allowed to react with ethoxyacetylene in the presence of an amino acid ester, the phthaloyl derivative is obtained in good yield.143... 

Similarly, sulfoximines 11a and lib afford a set of four diastereomers 13-16, respectively51. Adducts 13-16 are obtained with good to excellent yield and endo addition is generally favored. For 15a, 16a the exo addition shows no diastereodifferentiation. The mixture of diastereomers 13b- 16b obtained by cycloaddition of the A -phthaloyl derivative lib is difficult to separate2. 

The ester enolate Claisen rearrangement of (Z)-crotyl /V-tm-Boc-glycinate has been applied to the synthesis of lactone hydrochloride 4, the hydrolysis product of the amanita mushroom toxins a- and / -amanitin487. The rearrangement and the iodolactonization of the A -phthaloyl derivative are the stereocontrolling steps in this reaction sequence. 

Tri-O-benzyl-L-galactitol was converted into the isopropylidene mesylate 24. Treatment of 24 with lithium azide in DMF gave the azide 25 with inversion of the configuration. Reduction of the azide 25 with lithium aluminum hydride gave the amine 26 To protect the amino group, N-ethoxycarbonylphthalimide was used with triethylamine as solvent to give the phthaloyl derivative 27... 

Aromatic amines, like phenols, are very easily nitrated. However, primary and secondary amines in particular readily undergo oxidative side reactions, so that it is advisable to protect the amino group by acylation or by conversion by an aldehyde into the Schiff base. Even using a large excess of sulfuric acid protects the amino group to a considerable extent, owing to formation of the ammonium salt, but then entry of the nitro group is directed to a considerable extent into the meta-position. The usual A-acyl derivative is the acetyl compound, but benzoyl, /7-toluenesulfonyl, oxalyl, ethoxycarbonyl (from chloro-formic ester), and phthaloyl derivatives are also used. 

The ORD spectra of a few iV-phthaloyl derivatives of dipeptides have been reported (Djerassi et ai, 1961a). It was found that the sign of the Cotton effect is governed by the absolute configuration of the NH 2-terminal amino acid negative for the l configuration and positive for the d configuration. 

Another successful catalytic enantioselective 1,3-dipolar cycloaddition of Qf-diazocarbonyl compounds using phthaloyl-derived chiral rhodium(II) catalysts has been demonstrated [ill]. Six-membered ring carbonyl ylide formation from the a-diazo ketone 80 and subsequent 1,3-cycloaddition with DMAD under the influence of 1 mol % of dirhodium(II) tetrakis[M-benzene-fused-phthaloyl-(S)-phenylvaline], Rh2(S-BPTV)4 101 [112], has been explored to obtain the cycloadduct 102 in up to 92% ee (Scheme 31). 

Orange-rM pnsms m AcOEt. M.p. 118-5°. Very sol. CgHg. Sol. hot EtOH, AcOEt. Red. — 3 4-tolylenediamine p-toluidine. Phthalic anhydride —> phthaloyl deriv., m.p. 220°. 

The best results were obtained by using the phthaloyl derivative (+)63 because this protective group allows the regioselective preparation of both a- and P-phthaloyl alanines by simply changing the ligand on nickel (Entries 9 and 11). Furthermore, with this protective group the decar-... 

Another carbohydrate, 2,3-O-isopropylidene-D-erythronolactone (6.280), was prepared from isoascorbic acid SS and then converted to phthaloyl derivative... 

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