Alcohol moiety

Pyrethroids from Chiysanthemic Acid. The unsaturated side chains of the aHethrolone alcohol moieties of the natural pyrethrins are readily epoxidized by microsomal oxidases and converted to diols, thus detoxifying the insecticides. Esterification of chrysanthemic acid (9), R = CH3, with substituted ben2yl alcohols produces usehil insecticides barthrin [70-43-9J, 2-chloro-3,4-methylenedioxyben2yl (+)-i7j ,/n7 j -chrysanthemate, and dimethrin [70-38-2] 2,4-dimethylben2yl (+)-i7j ,/n7 j -chrysanthemate. These have alimited spectmm of insecticidal activity but are of very low mammalian toxicity, ie, rat oralLD s >20,000 mg/kg. 

Pyrethroids with Modified Chrysanthemate Esters. Newer pyrethroids incorporate optimized chrysanthemic acid components to retard detoxication by microsomal oxidases and these are esterified with a variety of optimized alcohol moieties therefore increasing persistence. 

Pyrethroid Esters of Benzene Acetate. These insecticides have more extensive stmctural optimization in both acid and alcohol moieties. Fenvalerate [51630-58-17, a-cyano-(3-phenoxyphenyl)methyl (+)-(2R,5)"Ct"isoprop5i-4-chlorophenylacetate (24) d 1.17, vp 1.4 p.Pa at 25°C), a mixture of four isomers, is soluble in water to 0.3 mg/L The rat oral LD q is 450 mg/kg. Esfenvalerate [66230-04-4] is the (+)-2-(i, 5)-isomer (mp 59°C). The rat LD qS are 75, 458 (oral), and the rabbit dermal LD q is 2000 mg/kg. These pyrethroids are widely used general-purpose insecticides for field, vegetable, and fmit crops. 

Transesterification of methyl methacrylate with the appropriate alcohol is often the preferred method of preparing higher alkyl and functional methacrylates. The reaction is driven to completion by the use of excess methyl methacrylate and by removal of the methyl methacrylate—methanol a2eotrope. A variety of catalysts have been used, including acids and bases and transition-metal compounds such as dialkjitin oxides (57), titanium(IV) alkoxides (58), and zirconium acetoacetate (59). The use of the transition-metal catalysts allows reaction under nearly neutral conditions and is therefore more tolerant of sensitive functionality in the ester alcohol moiety. In addition, transition-metal catalysts often exhibit higher selectivities than acidic catalysts, particularly with respect to by-product ether formation. 

The reactions of esters have been reviewed (11—15). Because of the large number of possible acid and alcohol moieties, the chemical properties of esters may differ considerably. Only typical reactions appHcable to the majority of esters are described in the following sections. 

Formate esters generally become less toxic as the alcohol moiety increases up to C. With this increase in alkyl si2e, the LD q (oral, rabbit) increases from 1.62 g/kg for methyl formate to 3.0 g/kg for isoamyl formate [110-45-2]. In comparison, both aHyl and vinyl formates are more toxic than their saturated analogues. 

Plasticizers. Plasticizers are materials that soften and flexibilize inherently rigid, and even britde polymers. Organic esters are widely used as plasticizers in polymers (97,98). These esters include the benzoats, phthalates, terephthalates, and trimeUitates, and aUphatic dibasic acid esters. Eor example, triethylene glycol bis(2-ethylbutyrate) [95-08-9] is a plasticizer for poly(vinyl butyral) [63148-65-2] which is used in laminated safety glass (see Vinyl POLYMERS, poly(vinyl acetals)). Di(2-ethyUiexyl)phthalate [117-81-7] (DOP) is a preeminent plasticizer. Variation of acid and/or alcohol component(s) modifies the efficacy of the resultant ester as a plasticizer. In phthalate plasticizers, molecular sizes of the alcohol moiety can be varied from methyl to tridecyl to control permanence, compatibiUty, and efficiency branched (eg, 2-ethylhexyl, isodecyl) for rapid absorption and fusion linear (C6—Cll) for low temperature flexibiUty and low volatility and aromatic (benzyl) for solvating. Terephthalates are recognized for their migration resistance, and trimeUitates for their low volatility in plasticizer appHcations. 

Long-chain polyisoprenoid. molecules with a terminal alcohol moiety are called, polyprenols. The dolichols, one class of polyprenols (Figure 8.18), consist of 16 to 22 isoprene units and, in the form of dolichyl phosphates, function to carry carbohydrate units in the biosynthesis of glycoproteins in animals. Polyprenyl groups serve to anchor certain proteins to biological membranes (discussed in Chapter 9). 

A conveniently short synthesis of a1prostadi1 begins with a mixed aldol assembly of the requisite cyclopentenone 13. This product is then oxidatively cleaved with periodate-permanganate and the alcohol moiety is protected as the tetra-hydropyranyl ether (14). Aqueous chromous sulfate satisfactorily reduces the olefinic linkage and the trans stereoisomer 15 predominates after work-up. The remainder of the synthesis of involves the usual steps, through 16 to with the exception that thexyl tetrahydrolimonyllithium borohydride is used to reduce the C-15 keto moiety so as to produce preferentially the desired C-15S stereochemistry. 

Gemeprost (73 16.16-dimethvl-trans-A -prostaglandin-E]) is dramatically more potent on a dosage basis as an abortifacient than prostaglandin E2 itself and has fewer side effects. The gem-dimethyl groups at C-16 protect the alcohol moiety at C-15 from rapid metabolic oxidation. 

It was demonstrated that when a better leaving group than lithium oxide (Li20) is present at the a-position (e. g., epoxide 125 Scheme 5.27), alkene formation occurs with retention of the alcohol moiety [44]. 

Compared to the lithium enolates of l and 5, the higher stereoselectivity obtained by the Mukaiyama variation is, in general, accompanied by reduced chemical yields. The chiral alcoholic moieties of the esters 3 and 7 can be removed either by reduction with lithium aluminum hydride (after protection of the earbinol group) or by aqueous alkaline hydrolysis with lithium hydroxide to afford the corresponding carboxylic acid. In both cases, the chiral auxiliary reagent can be recovered. 

Pyrethrins are esters and therefore may be discussed in terms of the chrysanthemumic or pyrethric moiety and the keto alcohol moiety. 

Pyrethrolone and cinerolone make up the keto alcohol moiety of the pyrethrins. Both of these keto alcohols have one asymmetric carbon at the 4-position and a double bond in the side chain which is capable of cis-trans isomerism in the 2-position. It is possible, therefore, to have four stereoisomers for each keto alcohol. Katsuda et al. (22) show that only the ( + ) form occurs in the natural esters. Elliott (8) has shown recently, by a new procedure developed to obtain pure ( + ) pyrethrolone, that the hitherto unidentified prye-throlone C is in reality pyrethrolone contaminated with thermally isomerized material. (+) Pyrethrolone forms a crystalline monohydrate from which the pure alcohol is obtained. The natural configurations of the keto alcohols in the esters are insecticidally more active, as is the case with the acid moiety. 

This is interesting when one considers the effect of synergists on the synthetics. All of the synthetics mentioned above are based on chrysanthemum monocarboxylic acid and in the case of allethrin, cyclethrin, and furethrin on the alcohol moiety there is only one double bond. When checked against the standard synergists, these synthetics do not show the degree of synergism shown by pyrethrins and this may be because of the fact that there is only one double bond for epoxidation, compared with two in the pyrethrolone radical, and therefore the synergist would not block this epoxidation step as effectively. 

Figure 6.44 Types of enzyme-catalyzed reactions leading to enantiopure alcohols. Stereogenic centers are included in the alcohol moiety, as indicated by an asterisk.).

Selenides (R2Se) can be oxidized to selenoxides and selenones. It is possible to oxidize a thioether to a sulfoxide in the presence of an alcohol moiety using MnOa/HCl. ... 

The 10 OC route was followed for the synthesis of tetrahydrofurans possessing a y-amino alcohol moiety 247 (Eq. 29) 118]. Aldoximes 21a-f (see also Eq. 3 and Table 2), when heated in benzene in a sealed tube at 110 -120 °C for 6 h, underwent smooth intramolecular cycloaddition to the tetrahydrofuranoisoxazo-lidines 246a-f in 70-83% yield (Eq. 29). This ring closure proceeded stereo-specifically to generate three adjacent stereogenic centers. LAH reduction of 246 b resulted in isolation of stereospecifically functionalized tetrahydrofuran derivative 247b in 75% yield. 

Figure 8 Structure of immunogen haptens for pyrethroids with spacer arm attachment at the a-position of the alcohol moiety. Since the whole pyrethroid molecule is available for recognition by the antibody, assays resulting from these immunogens were selective for the parent pyrethroids...

An 8-phenylmenthol ester was employed as the chiral auxiliary to achieve enantioselectivity in the synthesis of prostaglandin precursors.83 The crucial features of the TS are the anti disposition of the Lewis acid relative to the alcohol moiety and a tt stacking with the phenyl ring that provides both stabilization and steric shielding of the a-face. 

The spin label in question may as well be in the carboxylic acid fragment as in the alcohol moiety. Photoreactive esters bear azido groups in their carboxylic acid moieties. The esterification of nitroxide- or azide-bearing carboxylic acids with complex alcohols and CDI is illustrated in Table 3-6 by way of some examples. 

For carboxyl terminal determination of peptides by means of CDI the terminal carboxylic acid group of the peptide is selectively reduced with sodium dihydrobis(2-methoxy-ethoxy)aluminate to an alcohol. Subsequent conversion of the amino alcohol moiety with CDI yields an 7V-acyl-2-oxazolidone derivative, from which the oxazolidone unit can be easily removed and characterized.[56]... 

The donor and acceptor classes illustrated with hydrocarbons can be directly extended to include hetero-atoms. For example, the alcohol moiety q /H would be a 4e donor, of the same orbital symmetry as the ethane moiety Similarly the carbonyl... 

This procedure is not a domino process in its strictest definition, but since the oxidant tert-butyl hydroperoxide is added after allylation is complete, it is a very impressive and useful transformation for the rapid assembly of three contiguous stereogenic centers, including a tertiary alcohol moiety. 

In another approach, the alcohol moiety, formed by an enzymatic hydrolysis of an ester, can act as a nucleophile. In their synthesis of pityol (8-37a), a pheromone of the elm bark beetle, Faber and coworkers [17] used an enzyme-triggered reaction of the diastereomeric mixture of ( )-epoxy ester 8-35 employing an immobilized enzyme preparation (Novo SP 409) or whole lyophilized cells of Rhodococcus erythro-polis NCIMB 11540 (Scheme 8.9). As an intermediate, the enantiopure alcohol 8-36 is formed via kinetic resolution as a mixture ofdiastereomers, which leads to the diastereomeric THF derivatives pityol (8-37a) and 8-37b as a separable mixture with a... 

Ti compounds also promote epoxidation of olefins, mainly allyl alcohol moieties in the presence of peroxides (Scheme 32).1 5... 

New procedures to the formation of l,4-dioxa-7,l 1-dithiacyclotridecan-9-ol and 1,4,7-trioxa-10,14-dithiacyclohexadecaen-12-ol utilized 2,3-dibromopropanol with either (CH2OCH2CH2SH)2 or 0(CH2CH20CH2CH2SH)2 with Li2C03 in aqueous EtOH the procedure was shown to proceed via an oxirane intermediate <06CHC206>. The convenient oxidation of the above tridecan-9-ol to the l,4-dioxa-7,ll-dithiacyclotridecan-9-one was accomplished by a Swem oxidation at low (-70 °C) temperatures the alkylation and acylation of the ring alcohol moieties were also reported therein. 

The specificity of pectinesterase is not so marked with respect to the alcohol moiety of the ester, as it hydrolyzes ethyl esters of D-galacturonans at a rate 6-16% that of de-esterification of the methyl esters.36 Citrus natsudaidai pectinesterase de-esterifies the ethyl esters of pectic acid at a rate l/5th to l/7th of that for the methyl esters the propyl and allyl esters are attacked at l/20th to l/80th of the rate.38 The tomato, citrus, alfalfa, and papaya pectinesterases do not hydrolyze the glycol and glycerol esters of pectin.39... 

The first significant success in creating a photostabilized pyrethroid with high insecticidal activity was achieved through use of the 3-phenoxybenzyl alcohol moiety. A further step was the finding that 2-aryl-3-methylbutyric acid esters of pyrethroid alcohols were both photostable and... 

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