Alkoxyalkyl Esters

Hydroxyalkylthiazoles are also obtained by cyclization or from alkoxyalkyl-thiazoles by hydrolysis (36, 44, 45, 52, 55-57) and by lithium aluminium hydride reduction of the esters of thiazolecarboxylic acids (58-60) or of the thiazoleacetic adds. The Cannizzaro reaction of 4-thiazolealdehyde gives 4-(hydroxymethyl)-thiazole (53). The main reactions of hydroxyalkyl thiazoles are the synthesis of halogenated derivatives by the action of hydrobroraic acid (55, 61-63), thionyl chloride (44, 45, 63-66), phosphoryl chloride (52, 62, 67), phosphorus penta-chloride (58), tribromide (38, 68), esterification (58, 68-71), and elimination that leads to the alkenylthiazoles (49, 72). 

Dal Pozzo F, Andrei G, Lebeau I, Beadle JR, Hostetler KY, De Clercq E, Snoeck R (2007) In vitro evaluation of the anti-orf virus activity of alkoxyalkyl esters of CDV, cCDV and (S)-HPMPA. Antiviral Res 75 52-57... 

Wyles DL, Schooley RT, Kaihara KA, Beadle JR, Hostetler KY (2008) Anti-hepatitis C virus repli-con activity of alkoxyalkyl esters of (S)-HPMPA and other acyclic nucleoside phosphonates. In Abstracts of the 21st international conference on antiviral research, Montreal, QC, Canada, 13-17 April 2008. Antiviral Res 78 A21, no 15... 

A pro-drug approach for improving the pharmacokinetics of zanamivir has recently shown some promise. The alkoxyalkyl ester 23 of zanamivir, with long alkyl chains chosen to counteract the high hydrophUicity of the molecule, was reported to show significant protective effects against influenza (HlNl) infection in mice upon oral or intraperitoneal administration (Liu et al. 2007). 

The study of the transformation of 5-alkoxyalkyl-5-alkyl-l,3-dioxanes provided the first experimental evidence that the conformation of the reactant molecule plays a determining role regarding the direction of the catalytic reaction. The reason for the differing reaction directions clearly indicates that the conformers adsorb in different ways.32 The 5-alkoxyethyl isomers can exist in their chair conformations (1 and 2 in Scheme 4.12). The main reaction of the adsorbed surface species is the formation of an ester (3) by the rupture of the C-O bond in the ring. In one of the two isomers (1) the R2-0 group can also be adsorbed and this adsorption leads to a smaller ester molecule (4). 

An examination of some of the factors influencing the chemical and enzymatic hydrolysis of nicotinic acid esters was undertaken [45-48]. Twenty-five esters of nicotinic acid were prepared whose pro-moiety was a simple alkyl (unbranched, sec-, or /er/-alkyl), a chloroalkyl, a hydroxyalkyl, an alkoxyalkyl, a carbamoylmethyl, an aminoalkyl, a cycloalkyl, an arylalkyl, or an aryl group (Table 8.5). 

Detailed investigations indicate that the enolization process (LDA, THF) affords enolates 37 and 38 with at/east 97% (Z)-stereoselection. Related observations have recently been reported on the stereoselective enolization of dialkylthioamides (38). In this latter study, the Ireland-Claisen strategy (34) was employed to assign enolate geometry. Table 10 summarizes the enolization stereo selection that has been observed for both esters and amides with LDA. Complementary kinetic enolization ratios for ketonic substrates are included in Table 7. Recent studies on the role of base structure and solvent are now beginning to appear in the literature (39,40), and the Ireland enolization model for lithium amide bases has been widely accepted, A tabular survey of the influence of the ester moiety (ORj) on a range of aldol condensations via the lithium enolates is provided in Table 11 (eq. [24]). Enolate ratios for some of the condensations illustrated may be found in Table 10. It is apparent from these data that ( )-enolates derived from alkyl propionates (Rj = CH3, t-C4H9) exhibit low aldol stereoselectivity. In contrast, the enolates derived from alkoxyalkyl esters (Rj = CHjOR ) exhibit 10 1 threo diastereo-... 

Carboxylic acids are protected as their esters such as methyl esters, tert-hutyl esters, allyl esters, benzyl esters, phenacyl esters and alkoxyalkyl esters. The esters are formed by the reaction of carboxylic acid with alcohol, and the reaction is known as esterification. 

Alkoxyalkyl esters and silyl esters are also easily prepared and cleaved. For example, 2-(trimethylsilyl)ethoxymethyl esters are usually cleaved with HF in acetonitrile by fluoride ion. 

The addition of alcohols to N-alkylidene selenoamides generated in situ leads to N-alkoxyalkyl selenoamides [84]. The substitution reaction of alkoxy groups of selenoesters [RC(Se)OR ] with aluminum thiolates or selenolates proceeds smoothly to give the corresponding esters [RC(Se)SR, RC(Se)SeR ] [7a, 85], whereas the addition of thiols to selenoaldehydes takes place at the selenium atom to afford selenenesulfides (RCH2SeSR ) [86]. 

A number of 1-alkoxyalkyl esters (acylats) such as 1-methoxyethyl-acetate, CH,CO,CH(OCH,)CHj, have been made from 1-alkoxyalkyl chlorides and sodium salts of carboxylic acids. ... 

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