Esters pivaloyl

Penicillin e.g., pivaloyl ester short-chain alkyl esters, e.g., methyl, ethyl, isopropyl, hydroxypropyl, and butyl esters Acyloxymethyl ester, e.g., pivaloyloxymethyl ester, 2,14,15... 

These relations both demonstrate the inhibition of formation of the tetrahedral state which can be clearly attributed to steric crowding. Such a correlation as (5) confirms the attack at the neighbouring carbonyl group and this intramolecular catalysis for all this series. The activation parameters for the alkaline hydrolysis of these esters were also measured and are shown in Table 1. The enthalpies of activation of the 2-formyl, 2-acetyl, 2-propionyl, 2-isobutyryl and 2-pivaloyl esters are exceptionally small. These are... 

Bufotenine has been found to be behaviorally inactive, or only weakly active, in most animal studies, although at 15 mg/kg, it did produce the head-twitch resonse in mice (43). It was also behaviorally active in experiments in which the blood-brain barrier was bypassed (78). Acylation of the polar hydroxy group of bufotenine increases its lipid solubility (65,74) and apparently enhances its ability to cross the blood-brain barrier (64). For example, O-acetylbufotenine (5-acetoxy-N,N-dimethyltryptamine 54) disrupted conditioned avoidance behavior in rodents (65) and produced tremorigenic activity similar to that elicited by DMT (37) or 5-OMeDMT (59) when administered to mice (64). In this latter study, a comparison of brain levels of bufotenine after administration of O-acetylbufotenine with those of DMT and 5-OMeDMT revealed bufotenine to be the most active of the three agents, based on brain concentration. The pivaloyl ester of bufotenine also appears to possess behavioral activity, since stimulus generalization was observed when this agent was administered to animals trained to discriminate 5-OMeDMT from saline (74). 

One must be careful not to generalize from the above discussion that hydrolysis of pivaloyl esters will always be slow. Indeed, a notable exception may well exist for monoesters of catechols, where intramolecular catalysis accelerates hydrolysis. This was seen for L-3-[3-hydroxy-4-(pivaloyl-oxy)phenyl] alanine (8.81 4-pivaloyl-L-dopa), a potentially valuable prodrug of L-dopa [114], When given to rats and dogs, 4-pivaloyl-L-dopa displayed markedly longer duration of action and a higher bioavailability of L-dopa than the drug itself complete conversion to L-dopa was noted in rat. The... 

Cleavage of ethers. A few reports have mentioned that acyl iodides can cleave ethers in the absence of a Lewis acid. Since acyl iodides are not readily available, Oku et al. have used Nal and an acyl chloride as a possible equivalent. In any case, the system does cleave both cyclic and acyclic ethers selectively at the less substituted a-C—O bond. Although any acyl chloride can be used, use of pivaloyl chloride is particularly attractive because the resulting pivaloyl esters are readily hydrolyzed. Indeed this system is particularly useful for deprotection of methyl ethers. 

Toward the total synthesis of (—)-ascofuranone (Scheme 3.45), an antibiotic with hypolipidemic, antihypertensive, and antitumor properties, several improvements have been made. A pivaloyl ester was used instead of an acetyl ester.71 More... 

The higher steric demand of carbohydrate templates containing the pivaloyl ester usually results in a higher stereoselectivity in their reactions compared to those of the acetyl-protected analogues [13]. 

The stereochemical outcome of the addition was explained in terms of steric interactions, as illustrated in Scheme 10.64. The carbonyl groups of both the crotonyl and pivaloyl esters are co-ordinated by the magnesium organocuprate or the magnesium halides formed during the reaction. The crotonyl ester 191 probably prefers an -rran -conformation. As the /-face of the double bond is shielded by the bulky pivaloyl group, the cuprate reagent approaches from the less... 

The bulky pivaloyl group has been used as a protecting group in the synthesis of acylated nucleosides [247], monosaccharides, and disaccharides [248]. The pivaloyl esters are usually highly crystalline compounds, its position in a molecule is easily detectable by NMR, and it can be... 

A limitation in the use of pivaloyl esters as protecting groups in a polyfunctional system is the harsh condition required for its cleavage (especially at sterically hindered secondary centers). The 4-acetoxy-2,2-dimethylbutanoyl (ADMB) esters have been proposed as an alternative because they are easily prepared, show similar reactivity in carbohydrate acylations, and are removed under much milder conditions (catalytic quantity of DBU at room temperature) [254]. 

Wikstrom, H. Lindberg, P. Martinson, P. Hjorth, S. Carlsson, A. Hacksell, U. Svensson, U. Nilsson, J.L.G. (1978) Pivaloyl esters of N,N-dialkylated dopamine congeners. Central dopamine-receptor stimulating activity. J. Med. Chem. 21, 864-967. 

A second synthetic example illustrates several useful features of cation rearrangements. When 121 (OPiv is a pivaloyl ester) was treated with p-toluenesulfonic acid in methanol, protonation occurred at the more basic... 

Three additional protecting groups in this category are the mesitoate ester (OCOC6H22,4,6-trimethyl, O— Mes), the pivaloyl ester (OCO—f-Bu), and the para-methoxybenzoyl ester (OCO—C6H4-4-Me). The mesitoate ester is formed by reaction of an alcohol with mesitoyl chloride in the presence of pyridine or triethylamine. The main advantage of this ester is its stability to hydrolysis (pH 1-12), nucleophilic attack,... 

Of special interest is the formation of pivaloyl esters, because of the steric bulk of the pivaloyl group. Oscarson et al. [5] obtained the same results as for benzoylation when they subjected 1 to pivaloylation under microwave irradiation conditions, but with a a j8 ratio of 1 2 (Scheme 12.6). 

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