Chloroacetyl groups

The structure of ( )-169 is determined to have a ( )-3a,3a -bispyrrolo[2,3-(j] indole skeleton by carrying out X-ray single crystallographic analysis of its derivative 252 (99H1237). Compound 252 is obtained from ( )-169 by the following sequence of reactions (1) alkaline hydrolysis of ( )-169 to 249 (88%), (2) conversion of 249 to 251 (71%) by treatment with NaH and chloroacetyl chloride, (3) substitution of chlorine on the chloroacetyl group for acetate 252 (93%) by the reaction with NaOAc. 

Answer The chloroacetyl group can be disconnected first to leave (13) - just the kind of compound we have been discussing. The strategy used in the published synthesis " was the second of the two we considered. 

Resistance of house flies (Musca domestica) to DDT was attributed to its transformation to the nontoxic DDE, and the enzyme that carries the dehydrochlorination has been characterized in DDT-resistant flies (Lipke and Kearns 1959a,b). The herbicide alachlor is transformed by chironomid larvae by O-demethylation followed by loss of the chloroacetyl group to produce 2,6-diethylaniline... 

The chloroacetyl group in 6 was removed by treatment with hydrazine dithiocarbonate in acetonitrile to give 7 in 887 yield (c 1.5, CHCI ). 

Numerous researchers have employed thiols as weak bases in the thioalkylation reaction to ligate unprotected peptides with a haloacetyl group to form thioethers at pH 7 8.5[90 91 131-133 or thioesters at acidic to basic conditions. 108"110 Of these two reactions, thioether formation is often the choice because thioesters suffer from instability in aqueous basic conditions. Haloacetyl derivatives, either as carboxylic acids or active esters, can be attached to either the N-terminal or side-chain amines during the stepwise solid-phase synthesis of either the peptide or the core and are stable to either HF or TFA cleavage conditions. Capping an amino group with a chloroacetyl group is compatible with Fmoc chemistry when used at a terminal step. 

A reaction of acetylacelonc <3) with chloroacetyl chloride (4) takes place in the presence ol aluminum trichloride. In this process, an acetyl group is exchanged for a chloroacetyl group. Only atom C-3 in product 5 is therefore derived Irom acetylacelonc (3). 

Khorlin and co-workers [194, 195] prepared the blood-group A (type 1) tetrasaccharide (267) from the chloroacetate (272). This was condensed with 2-O-benzyl-3,4-di-O-p-nitrobenzoyl-a-L-fucopyranosyl bromide to give the 2-O-a-L-fucosyl derivative and after removal of the chloroacetyl group with thiourea the product was... 

Several mild reagents have been reported to cleave the chloroacetyl group, including 2-mercaptoethylamine (H2NCH2CH2SH), thiourea... 

H2NCSNH2) and hydrazinedithiocarbonate (H2NNHC(=S)SH)45 The latter reagents cleave the chloroacetyl group by a two-step one-pot reaction. For example, treatment with mercaptoethylamine results in substitution of the chloride followed by intramolecular cyclisation and cleavage (Scheme 2.15b). This reaction exploits the fact that intramolecular reactions are much faster than intermolecular reactions. 

To obtain the ethylene oxide type compound, /3-D-glucose pentaacetate was treated with an excess of phosphorus pentachloride to give 2-tri-chloroacetyl-3,4,6-triacetyl-/3-D-glucopyranosyl chloride.63,63a The tri-chloroacetyl group was removed by treatment with a dry ethereal solution of ammonia at 0°. From the product the anhydride may be obtained by... 

The N-hydroxy amino acid derivatives are likely to be applicable to other metalloproteases. Thermolysin is inhibited irreversibly at pH 7.2 by ClCH2CO-DL-HOLeu-OCH3 where HOLeu is N-hydroxyleucine (47). The inhibition reaction involves coordination of the hydroxamic acid functional group to the active-site zinc atom of the enzyme. This then places the chloroacetyl group adjacent to Glu-143, an essential catalytic residue of thermolysin (see Figure 9). An ester linkage is formed and the enzyme is inactivated irreversibly. This reagent also inactivated two neutral metalloproteases from B. subtilis, but reacted only very slowly with carboxypeptidase A (t1/2 > 3 d). 

Fig.V.2. Histogram showing the distribution of the w-35C1-NQR frequencies, v, around the average frequency, of all chloroacetyl groups a) in chloroacetanilides,...

Grass weed Animals. Rapidly oxidized by rat liver controller microsomal oxygenases via dechlorination, O-demethylation and side-chain oxidation Plants. Metabolism involves natural product conjugation of the chloroacetyl group and hydrolysis and sugar conjugation at the ether group. Final metabolites are polar, water-soluble, and nonvolatile... 

D. J. Gale and J. F. K. Wilshire, Fibre-reactive basic dyes. I. Polymethine dyes containing the N-chloroacetyl group, J. Soc. Dyers Colour., 1974, 97-100. 

In the foregoing examples, the latent nucleophiles were intrinsic to the protecting group and as such were part of the molecular baggage that had to be carried through a synthetic sequence. Scheme 8.2855 illustrates the cleavage of an N-chloroacetyl group in which the nucleophile is appended at the time of deprotection by 5-alkylation of piperidinethiocarboxamide.56 Thiourea will accomplish the same task.57,58... 

Krohnke-King oxidative degradation of acetyl and chloroacetyl groups at various positions led to carboxylic acids. 

Chloroacetylated oligotuftsin H-[Thr-Lys-Pro-Lys(ClAc)-Gly]4-NH2 was dissolved in 0.1 M Tris-HCl buffer (pH 8.2) in a peptide concentration of 1 mg/ mL. The 20-mL tube used for the reaction was filled up fully and closed tightly. The epitope peptide synthesized by the procedure presented in Subheading 3.1.1. (H- LKN1cADPNRFRGKDL22C-NH2) was added to the mixture in 1-2 mg aliquots every 15 min (see Note 5). In this way low concentrations of the epitope peptide prevented disulfide bond formation. The coupling was followed by analytical HPLC that showed the incorporation of the epitope peptide. The reaction was completed in 2 d using two equivalents of epitope peptide to each chloroacetyl group (see Note 6). The branched chimeric peptide was purified on RP-HPLC (60% yield) (see Note 7) and after lyophilization the purified product was characterized by analytical HPLC, amino acid analysis and mass spectrometry. 

Bromoacetyl groups cannot be used for thioether bond formation with cysteine residue in the presence of free amino groups. Only the chloroacetyl group is suitable for this purpose. 

First, we prepared a derivative of polypeptide SAK possessing chloroacetyl groups in multiple copies at the a-amino groups of the branches. This compound... 

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