Positional selectivity acylation

Much of the current interest in making simple derivatives of (+ )-castanospermine (239) can be traced to a seminal publication in 1989, which showed that the alkaloid s anti-HIV activity could be increased by as much as twenty times upon esterification (216). Positionally selective acylation procedures usually involve sequential protection, acylation, and deprotection steps e.g. the preparation of esters at the C-6 and C-7 (217) or the C-8 hydroxy groups (218). Also of interest are procedures that take advantage of enzyme-catalyzed transesterification with activated esters, e.g. the use of subtilisin for ester formation at C-1, pancreatic porcine lipase for preferential reaction at C-6 and C-7 (219-221), and cross-linked enzyme crystals (CLECs) of subtilisin for making the potentially valuable antitumor agent 1-0-butanoylcastanospermine (222). A cautionary note was sounded, however, when it was observed that 6-0-acyl castanospermine esters could equilibrate to a mixture of... 

Regioselective Acylation of Hydroxy Compounds. AUphatic diols can be selectively acylated at the primary position by a number of Upases in nonaqueous solvents. For example, PPL suspended in solutions of various diols in ethyl carboxylates catalyzes transesterification in a highly regioselective manner, producing primary monoesters in up to 97% yield (93). Similarly, chloramphenicol [56-75-7] (72) (R = NO2) can be acylated by a number of Upases to produce optically pure, water-insoluble 3-0-palmitate in a highly selective manner (94). 

ACOCH2CCI3, pyridine, porcine pancreatic lipase, 85% yield.These studies examined the selective acylation of carbohydrates. Mannose is acy-lated at the 6-position in 85% yield in one example. 

Table 10.10. Substrate and Position Selectivity in Friedel-Crafts Acylation Reactions...

One other feature of the data in Table 10.10 is worthy of further comment Notice that alkyl substituted acylium ions exhibit a smaller ortho para ratio than the various arpyl systems. If steric factors were dominating the position selectivity, one would expect the opposite result A possible explanation for this feature of the data could be that the aryl compounds are reacting via free acylium ions, whereas the alkyl systems may involve more bulky acyl chloride-catalyst complexes. 

Regioselective Acylation of Hydroxy Compounds. Aliphatic diols can be selectively acylated at the primary and secondary positions by a number of lipases in nonaqueous solvents... 

Dihydropyridines substituted at the 3- and/or 4-positions undergo selective acylation with trichloroacetic anhydride to give 5-trichloroacetyl-l,4-dihydropyridines 136, which are easily converted by the haloform reaction to esters 137 (Scheme 37) <1998TL9275, 2002T8099, 2003TL4711>. Hydrogenation, over platinum oxide, of... 

Benzothiazole is acylated selectively in the 2-position by acyl radicals generated from a variety of aldehydes under the influence of the redox system f-butylhydroperoxide-ferrous sulfate. The nucleophilicity of acyl radicals is confirmed by the higher reactivity of 6-nitrobenzothiazole. The reaction, which could detect acyl radicals in the oxidation of aldehydes by various oxidizing agents, could serve as a diagnostic test for the presence of such radicals (71JCS(C)1747). 

Indoles 371 are selectively acylated at the 3-position to give high yields of compounds 372 on treatment with a wide variety of acyl chlorides in dichloromethane in the presence of chloro(diethyl)aluminium or chloro(dimethyl)-aluminium. The reaction proceeds under mild conditions (at 0 °C or rt, mainly for 1.5 h) and is applicable to indoles bearing various functional groups (both acid and base sensitive indoles) without NH protection (Equation 84) <20000L1485>. 

ACYL MIGRATION PLAGUES 1,3-POSITIONAL SELECTIVITY OF LIPASES... 

Good selectivity among secondary carbohydrate alcohols has been achieved, but the regiochemistry is structure-dependent. a-Methylglucoside can be selectively acylated at the 2,6-positions in 89% yield and a-methyl 4,6-0-ben-zylidineglucoside can be selectively acylated at the 2-position in 77% yield."... 

A combination of metal ions can be used in selective acylation of amino groups in consecutive sequence of reactions as is described in the synthesis of 1-C-hydroxy-methylkanamycin B [23]. In this synthesis, the amino groups of kanamycin B (5) at positions 3, 2, and 6 were first protected with di-ferf-butyldicarbonate in the presence of Zn(II), and then the amino group at the 1-position was selectively protected... 

Different amino acid and peptide derivaties were used to synthesize a series of aminoacyl and dipeptidyl derivatives of kanamycin A and netilmicin modified at the 1-, and 6 -amino groups by selective acylation of the copper complexes of these antibiotics. However, none of these modified compounds were active against either gram-positive or gram-negative bacteria [139]. Recently, in a report from Abbott... 

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