Cyclic monoesters

Such stereoselectivity was also observed with cyclic monoester 507 the C=C bond migrated from the /3,y- to the a,/3-position [193, 228-230]. 

This review aims at reporting on the synthesis of aliphatic polyesters by ROP of lactones. It is worth noting that lactones include cyclic mono- and diesters. Typical cyclic diesters are lactide and glycolide, whose polymerizations provide aliphatic polyesters widely used in the frame of biomedical applications. Nevertheless, this review will focus on the polymerization of cyclic monoesters. It will be shown that the ROP of lactones can take place by various mechanisms. The polymerization can be initiated by anions, organometallic species, cations, and nucleophiles. It can also be catalyzed by Bronsted acids, Lewis acids, enzymes, organic nucleophiles, and bases. The number of processes reported for the ROP of lactones is so huge that it is almost impossible to describe aU of them. In this review, we will focus on the more... 

Several review articles on biodegradable polymers and polyesters have appeared in the literature [12-22]. Extensive studies have been carried out by Al-bertsson and coworkers developing biodegradable polymers such as polyesters, polyanhydrides, polycarbonates, etc., and relating the structure and properties of aliphatic polyesters prepared by ROP and polycondensation techniques. In the present paper, the current status of aliphatic polyesters and copolyesters (block, random, and star-shaped), their synthesis and characterization, properties, degradation, and applications are described. Emphasis is placed primarily on aliphatic polyesters derived by condensation of diols with dicarboxylic acids (or their derivatives) or by the ROP of cyclic monoesters. Polyesters derived from cyclic diesters or microbial polyesters are beyond the scope of this review. 

The boronic acid binding site can also be used for interactions with monoalcohols. In the presence of an ort/zo-hydroxymethylene group (see entry 1), an intramolecular cyclic monoester is formed (boronophthalide). This compound still has one hydroxyl group left for the esterification of monoalcohols, a reaction that can be used in the imprinting procedure [46,47,72]. Recently this method has been revived for the binding of steroid alcohols [73,986,c]. 

Neidlein, R., Keller, H., and Boese, R., Mild preparation of [l-[(benzyloxy)imino]alkyl]phosphonic dichlorides. Application to the synthesis of cyclic phosphonic diesters and cyclic monoester amides. Heterocycles. 35, 1185, 1993. 

I, 2-position, seem to be less appropriate substrates for pig liver esterase (33-39 and 41-43). Finally, it seems noteworthy that transition metal complexes containing enantiotopic esters groups are also amenable to a highly selective pig liver esterase-catalyzed hydrolysis (71). Cyclic monoesters of Table 11.1-1, which can be obtained with other hydrolases as such or of opposite configuration, are contained in Tables... 

Cyclic diesters are often even better substrates forlipases and esterases than acyclic derivatives. Small-ring monoacetates (28, n — 1-3) are obtained in higher yield and ee than the larger derivatives (for 28, n = 4 is only 50%) (43). Hydrolysis of tetrahydrofuran diester results in monoester (29) of ee > 99% (44). 

Selective removal of the hydroxyl protecting groups included in this review is generally difficult to achieve and of little practical importance. Selective hydrolysis of cyclic orthoesters to give monoesters merits attention for its practical interest. 

Despite its widespread application [31,32], the kinetic resolution has two major drawbacks (i) the maximum theoretical yield is 50% owing to the consumption of only one enantiomer, (ii) the separation of the product and the remaining starting material may be laborious. The separation is usually carried out by chromatography, which is inefficient on a large scale, and several alternative methods have been developed (Figure 6.2). For example, when a cyclic anhydride is the acyl donor in an esterification reaction, the water-soluble monoester monoacid is separable by extraction with an aqueous alkaline solution [33,34]. Also, fiuorous phase separation techniques have been combined with enzymatic kinetic resolutions [35]. To overcome the 50% yield limitation, one of the enantiomers may, in some cases, be racemized and resubmitted to the resolution procedure. 

Enantioselective alcoholysis of racemic, prochiral, or meso cyclic anhydrides can be catalyzed by hydrolases, yielding the corresponding monoesters (Eigure 6.25). In most cases, the enantioselectivity was moderate ]75-77]. Organometallic catalysts or organocatalysts such as cinchona alkaloids are often more efficient than enzymes for the stereoselective ring opening of cyclic anhydrides. 

The dithiophosphonic acid monoesters, RP(OR )(S)SH can be conveniently prepared by cleavage of dimeric, cyclic diphosphetane disulfides, [RP(S)S]2 with alcohols, silanols, or trialkylsilylalcohols180 and then can be converted into metal complexes M[SPR(OR )]2 without isolation.181 The substituted ferrocenyl anion, (N3C6H4CH20)(CpFeC5H4)PS2 has been prepared in two steps from P4Sio, ferrocene and hydroxymethylbenzotriazole (and its salt was used for the preparation of some nickel and rhodium complexes).182 Zwitter-ionic ferrocenylditiophosphonates,... 

Fig. 9.10. Partial metabolic scheme of tris(2-methylphenyl) phosphate (9.44) showing hydrolysis to the diester 9.45, the monoester, and phosphate. Also shown is a reaction of oxidation to the hydroxymethyl analogue 9.46, followed by cyclization to the toxic cyclic phosphate 9.47...

Figure 2.11 Pyrrolizidine alkaloid toxins including (a) the pyrrolizidine nucleus, (b) retronecine, a less toxic monoester, and (c) jacobine, a highly toxic cyclic diester.

The phosphitylation procedure (step a) proceeds in the presence of EtN(i-Pr)2 (DPEA) and the subsequent oxidation by TBHP (step b). The cyclic phosphate is deprotected stepwise (steps c and d) and serves as a model for the physiological milieu . It has been possible to deliver phosphate monoesters via steps c and d in a controllable manner from cyclic phosphotri-esters at physiological pH. 

While a carboxylate anion is a potent nucleophile in an intramolecular reaction it is not powerful enough to displace methoxide or an unprotonated amine, unless the nucleophile and the carbonyl group are held even more rigidly than in the phthalate system. Kirby and Lancaster (referred to by Kirby and Fersht, 1971) have found that such displacement can occur in disubstituted maleate monoesters and amides. The estimated rate constant for cyclization of N-methyl dime thy Imaleamic acid [equation (41)] is 16,000 times greater than that for the unsubstituted compound. Below pH 5-6 hydrolysis of the cyclic anhydride becomes rate-determining. 

Figure 10. Rigid cyclic structure of (R,R)-diacyltartaric acid monoester from both enantiomers of propra-nolol showing changes in the conformation of the tartrate.

Cyclic mew-configurated 1,2-dicarboxylic acid dimethyl esters are excellent substrates for pig liver esterase90. Cyclopropanedicarboxylales have been studied not only for synthetic reasons, but also so that an active-site and/or substrate model of pig liver may be developed13 5. The results obtained, compounds 11-17, are a good demonstration of the scope and limitation of PLE in asymmetric synthesis. Enantiomeric excesses of the monoesters can be determined by conversion into the amides with (S)-l-phenylethylamine and analysis either by GC or H-NMR spectroscopy, whereas the absolute configuration rests on chemical correlation. 

A chiral recognition was observed in aminolysis of 3-acyl-4(R)-methoxycarbonyl-l,3-thiazolidine-2-thione, a derivative of (R)-cysteine, by racemic amines to give an optically active amide [(S)-excess] and amine [(R)-excess]264). In the reaction of cyclic meso-1,3-diols with chiral N-protected phenylalanyl chlorides, Yamada et al.26S) observed the preferential formation of one of the two possible diastereomeric monoesters, which has been used for the synthesis of optically active steroids 266) and prostaglandins 267). 

In addition to the hydrolysis of monoesters of phosphoric acid, the hydrolysis of diesters of phosphoric acid is also susceptible to metal ion catalysis, in particular by multivalent cations such as barium, stannous, and cupric ions. The diesters which undergo metal ion-catalyzed hydrolyses include open-chain diesters and cyclic diesters containing both five- and six-membered rings (54). 

In the presence of a cinchona alkaloid, certain cyclic carboxylic anhydrides with meso structures are converted to the chiral diacid monoesters in up to 76% ee (Scheme 10) 31). Quinine or cinchonidine and quinidine or cinchonine show opposite asymmetric induction. 

In the carbonylation of unconjugated dienes the nature of the products is influenced by reaction conditions. With Pd halides in ethanol at 100°C and 97 atm CO, 1,5-cyclooctadiene is successively carbonylated to the unsaturated monoester and then to the saturated diester (II). With (Ph3P)2PdCl2 in ethanol-HCl and 300-700 atm CO, the monoester is produced selectively at 60°C and the diester at 100°C (8). Finally, with (Bu3P)2PdI2 in THF at 150°C and 1000 atm CO, 1,5-cyclooctadiene undergoes transannular addition of CO to give a cyclic ketone in 40-45% yield (14, 15). The mechanism proposed involves a a-7r-cyclooctenyl... 

The ether extract containing the catalyst and neutral products was fractionally distilled (130°-160°C at 0.01 mm Hg). The soluble catalyst was concentrated in the pot residues. The distillation fractions were then chromatographed through a silicic acid column. Monoesters and cyclic ketones were eluted successively with 5 95 and 10 90 diethyl ether petroleum ether, and more polar material was eluted with 15 85 diethyl ether. -petroleum ether followed by pure diethyl ether. 

Acylated Corticoids. The corticoid side-chain of (30) was converted into the cyclic ortho ester (96) by reaction with a lower alkyl ortho ester RC(OR/)3 in benzene solution in the presence of yw/T7-toluene sulfonic acid (88). Acid hydrolysis of the product at room temperature led to the formation of the 17-monoesters (97) in nearly quantitative yield. The 17-monoesters (97) underwent acyl migration to the 21-monoesters (98) on careful heating with H+. In this way, prednisolone 17a,21-methylorthovalerate was converted quantitatively into prednisolone 17-valerate, which is a very active antiinflammatory agent (89). The intermediate ortho esters also are active. Thus, 17a,21-(l,-methoxy)-pentylidenedioxy-l,4-pregnadiene-llp-ol-3,20-dione [(96), R/ = CH3, R = C4H9] is at least 70 times more potent than prednisolone (89). The above conversions... 

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