A-Acyl derivatives

2 A Acyl Derivatives. - Oxazolines have been prepared in near quantitative yield by treatment of peracetylated 2-amino-2-deoxy-glycosyl halides with mercuric bromide and 2,4-collidine. C-Silyated byproducts 83 were formed in 

Reagents i, HOTs, H2O, MeCN ii, acylation iii, HOaC COaBn 3  

A similar approach has led to the synthesis of various o-glycosyl ester derivatives, e.g. 87 and an intermediate 89 for new lipidic disaccharide analogues 

The utility of several new AT-protecting groups has been described. The ready cleavage of the AT-pent-4-enoyl group with iodine in aqueous THF, and the utility 

Methyl 1-thio-p-glycosides of iV,A -diacetyl-2-amino-2-deoxy-D-glucose and -galactose, readily synthesized by AT-acetylation of the mono-AT-acetates (with AcCl, EtNPr 2) were effective glycosyl donors (with DMTST activation) and the products could be reconverted to mono-A -acetates by saponification (NaOMe, MeOH).  

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Most derivatives of aniline are not obtained from aniline itself, but ate prepared by hydrogenation of their nitroaromatic precursors. The exceptions, for example, /V-a1ky1ani1ines, /V-ary1ani1ines, sulfonated anilines, or the A/-acyl derivatives, can be prepared from aniline and have been discussed. Nitroanilines are usually prepared by ammonolysis of the corresponding chloronitroben2ene. Special isolation methods may be requited for some derivatives if the boiling points are close and separation by distillation is not feasible. Table 6 Hsts some of the derivatives of aniline that are produced commercially. 

The resulting acetyl compound is usually hydrolyzed with aqueous alkaU to give the free amine. Other A/-acyl derivatives may be used, particularly for the less soluble succinyl and phthaloyl products. The use of -nitrobenzenesulfonyl chloride, followed by reduction of the nitro to an amino function, is much more expensive and is rarely used. A/-Acetylsulfanilyl chloride [121 -60-8] is obtained by the chlorosulfonation of acetanilide [103-84-4] which is the basic material for most of the sulfonamides. 

The main type of hydrolysis reaction is that of halogenoaryl compounds to hydroxyaryl compounds, eg, the aqueous caustic hydrolysis of 0- and /)-chloronitrobenzene derivatives to nitrophenols. Another important reaction is the hydrolysis of A/-acyl derivatives back to the parent arylamine, where the acyl group is frequently used to protect the amine. 

Electrophilic aromatic substitution (Section 22.14) Arylamines are very reactive toward electrophilic aromatic substitution. It is customary to protect arylamines as their A/-acyl derivatives before carrying out ring nitration, chlorination, bromination, sulfonation, or Friedel-Crafts reactions. 

Similarly in epimeric transformation of A/ -acyl derivatives of 1,3-diphenyl-3-aminopropanol, the formation was accepted of 5,6-di-hydro-l,3-4H-oxazines with a conformation similar to (61). 

The smooth conversion of the enol acetate (151) into an A -acyl derivative (152) under extremely mild conditions points to the high acylating capacity of these esters. This cleavage of isoxazolium salts is also caused by other anions of carboxylic acids, and thus they can be readily converted to reactive enol esters. A very convenient and specific synthesis of peptides due to Woodward et is based on... 

Stereoselective hydrolysis of racemic l-(//-phenylacetylamino) alkanephos-phonic acids performed in the presence of penicillin acylase under the kinetic resolution conditions gave both the unreacted substrates and the products - the corresponding 1-aminophosphonic acids in high yields and with full enantioselec-tivity. The unreacted A -acyl derivatives were hydrolysed chemically and in this way each enantiomer of the free acid was obtained (Scheme 5). ... 

A. H. Kahns, H. Bundgaard, A-Acyl Derivatives as Prodrug Forms of Amides Chemical Stability and Enzymatic Hydrolysis of Various A-Acyl and A-Alkoxylcarbonyl Amide Derivatives , Int. J. Pharmaceut. 1991, 71, 31-43. 

A -Acyl derivatives of azepine like the iminostilbene 197 (Scheme 52) react in different ways depending on the nature of the N substituent if it is acyl, aroyl, or ethoxycarbonyl, the preferred reaction is dimerization on the other hand, N-tosyl compounds give PFR [154]. 

Rearrangements of 3-(o-aminophenyl)-l,2,4-oxadiazoles (44) or their A-acyl derivatives (R = acyl) to indazoles (45) require drastic conditions (Equation (10)) <82JCS(p1)759, 90ACH795>, for related reactions see also <82H(19)339,83T823>. 

Nucleophilic attack at sulfur is implicated in many reactions of 1,2,4-thiadiazoles <84CHEC-I(6)463> and in general soft nucleophiles attack at sulfur. For example, reaction of 3-hydroxy-5-phenyl-1,2,4-thiadiazole (23) with acetic anhydride in the presence of dbu at 130°C gives the thiazoles (31) and (32) <85JHC1497>. These products may be reasonably explained by the mechanism outlined in Scheme 9 in which the thiadiazole ring is opened by the acetic anhydride carbanion. There is some evidence that (32) may arise from attack of the carbanion on the A-acylated derivative (30a) (Scheme 9) <85JHC1497>. 

Alkaline hydrolysis of of 5,6-dihydro //-l,3-oxazines is a convenient method via which to obtain the corresponding 1,3-amino alcohols or their A -acyl derivatives <1996CC1629>. The yields are usually excellent, as in the transformation of 2,4,4-trimethyl-5,6-dihydro //-l,3-oxazine 130 to 3-amino-3-methylbutan-l-ol 131 (Equation 11) <2001JLR265>. 

The nonracemic 2/7-1,3-benzoxazin-4(3//)-one 202 was successfully applied as a chiral auxiliary in asymmetric transformations the titanium enolate-mediated aldol reactions of its A-acyl derivatives provided the products in high yields and with excellent diastereoselectivity <1996SL455, 1996TL5565>. 

The A -acyl derivatives of 4-substituted-3,4,5,6-tetrahydro-27/-l,3-oxazin-2-ones proved to behave as effective chiral auxiliaries in asymmetric enolate alkylations and aldol reactions, the stereoselectivities of which were found to be higher for 4-isopropyl than for 4-phenyl derivatives <2006OBC2753>. The transformations of 4-isopropyl-6,6-dimethyl-3-propa-noyl-3,4,5,6-tetrahydro-2/7-l,3-oxazin-2-one 251 to 252 or 253 proceeded with excellent diastereoselectivities (Scheme 47). 6,6-Dimethyl substitution within the oxazine ring facilitated exclusive exocyclic cleavage upon hydrolysis of the C-alkylated and the aldol products 252 and 253, to furnish a-substituted carboxylic acids 254 or a-methyl-/ -hydroxycarboxylic acids 256. 

It was shown previously that saturated 5(4//)-oxazolones or 2-oxazolm-5-ones with only one substituent at C-4 can be considered as the tautomeric form of saturated 5(2//)-oxazolones or 3-oxazolin-5-ones. These compounds can also be considered as amino acid derivatives and, indeed, cyclization procedures are the most commonly used to prepare these compounds. The cyclization reaction employs a variety of cyclodehydrating agents and the general method is shown in Scheme 7.23, with an A-acyl-a-amino acid being the most typical starting material used. In this way, 5(4//)-oxazolones derived from most natural amino acids 99 (R3 = H) have been obtained by heating the corresponding A-acyl derivatives in the presence of acetic anhydride. 

Enolates from l-acyl-2-pyrrolidinemethanols (A -acylprolinols) and their ethers are alkylated diastereoselectively, usually providing products in good to excellent diastereomeric ratios1-4. The most commonly employed auxiliaries are (S)-2-pyrrolidinemethanol (L-prolinol, 1), (S)-a,a-dimethyl-2-pyrrolidinemethanol (2) and (S)-2-(alkoxymethyl)pyrrolidines 3. For the preparation of these and the corresponding A -acyl derivatives, see Appendix. 

A few published pyrrolizidine syntheses cannot be classified under any of the above headings. An interesting synthesis of 3-substituted pyrrolizidines was described by Murakoshi.71 A-Acyl derivatives of ethyl (a-pyrrolidine)- -propionate can be converted by distillation over soda-lime into 3-substituted 2,3-dehydropyrrolizidines (121), which afford 3-substituted pyrrolizidines (122) on catalytic hydrogenation. 

The free bases of the 2-azabicyclo[2.2.0]hexanes are relatively stable to HC1 but their A-acyl derivatives (26) react rapidly to give ring-opened cyclobutenes (79JA6677). 

As free DHAs are highly unstable compounds that readily undergo hydrolysis, they have generally been synthesized as their A-acyl derivatives or carboxylic esters and amides. For this reason DHAs occur in nature primarily as A-acyl derivatives or as part of a peptide sequence. Free DHAs 2 (Scheme 1) have not been characterized most probably they exist as imines 1 and consequently they readily undergo hydrolysis to give the corresponding a-oxo acid 3 and ammonia. 

Coumarins, too, fluoresce, notably when an electron-releasing group is present at the 7-position. For example, A-acyl derivatives of some 7-aminocoumarins serve as fluorescent markers for the detection of proteinases (80MI22403). Coumarins show a propensity to absorb UV light and this results in a number of applications. A particularly simple illustration is the use of umbelliferone, 7-hydroxycoumarin, in sun-screen lotions. 

The term / -lactamase denotes an enzyme which catalyzes the hydrolysis of the amide bond in the /3-lactam ring of 6-amino-penicillanic acid (6-APA) or 7-amino-cephalosporanic acid (7-ACA) and of their A-acyl derivatives (2). Such derivatives are commonly referred to as penicillins [Fig. 1 (I) and cephalosporins Fig. 1 (III), (V), and (VII)], respectively. There is no evidence that any bond other than the amide bond in the intact nucleus of penicillin or cephalosporin is broken by the... 

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