From hydroxy esters

Enzymatic ring closure and opening lactone formation from hydroxy esters ring opening of anhydrides LPL, PFL lipase P, PFL... 

Alkylation of aldol type educts, e.g., /3-hydroxy esters, using LDA and alkyl halides leads stereoselectively to erythro substitution. The erythro threo ratio of the products is of the order of 95 5. Allylic and benzylic bromides can also be used. The allyl groups can later be ozonolysed to gjve aldehydes, and many interesting oligofunctional products with two adjacent chiral centres become available from chiral aldol type educts (G. Prater, 1984 D. Seebach, 1984 see also M. Nakatsuka, 1990, p. 5586). 

Alkynyl)oxiranes also react with carbon nucleophiles to afford furan derivatives. Furanes of different types are obtained depending on the structure of the substrates. 7-Methyl-2-ethynyloxirane (95) reacts with acetoacetate to give the furan 97 by the elimination of formaldehyde from the cyclized product 96. The hydroxy ester of the alkylidenefuran 98 and the corresponding lactone 99 are obtained by the reaction of i-methyl-2-(2-propynyI)oxirane[40, 42]. 

The reaLUons of phenyltetrafluorophosphorane with numerous silylated secondary or tertiary a- or (1-hydroxy esters, ketones, nitriles, ethers, nitro, and trichloromethyl derivatives have been investigated, the corresponding a or p fluoro derivatives are obtained in yields varying from reasonable to nearly quantitative [24, 25, 26, 27 The application of phenyltetrafluorophosphorane for fliiorination of silyloxy steroids has also been reported [28]... 

Butylethylidene and 1-phenylethylidene ketals were prepared selectively from the C4-C6, 1,3-diol in glucose by an acid-catalyzed transketalization reaction [e.g., Me3CC(OMe)2CH3, TsOH/DMF, 24 h, 79% yield PhC(OMe)2Me, TsOH, DMF, 24 h, 90% yield, respectively]. They are cleaved by acidic hydrolysis AcOH, 20°, 90 min, 100% yield, and AcOH, 20°, 3 days, 100% yield, respectively. Ozonolysis of the /-butylmethylidene ketal affords hydroxy ester, albeit with poor regiocontrol, but a more sterically differentiated derivative may give better selectivity, as was observed with the ethylidene ketal. ... 

A number of 5-hydroxy-2-oxotetrahydro-l,3-oxazine derivatives can also be formed from glycide esters of carbamic acid ... 

A terpene yielding isofenchyl alcohol on hydration, which Wallach considers to be one of the fenchenes, was artificially prepared by converting nopinone into a hydroxy ester by means of bromoacetic ester and zinc-dust. The hydroxy ester is dehydrated by potassium bisulphate, and so yields an unsaturated ester, which on saponification yields an acid from which the terpene results by distillation. This fenchene has the following characters —... 

Carbohydrate-derived titanium cnolates also provide yvn-x-amino-/l-hydroxy esters of high diastcrcomeric and enantiomeric purity. For this purpose, the lithium enolate derived from ethyl (2,2,5,5-tetramcthyl-2,5-disilapyrrolidin-l-yl)acetate is first transmctalated with chloro(cy-clopentadienyl)bis(1,2 5,6-di-0-isopropylidene-a-D-glucofuranos-3-0-yl)titanium and subsequently reacted with aldehydes.. vj-n-a-Amino-/ -hydroxy esters are almost exclusively obtained via a predominant /te-side attack (synjanti 92 8 to 96 4 87-98% ee for the xvn-adducts)623-b. 

The (/ ,/ )-A, 7V -bis[3,5-bis(trifluoromethyl)phcnylsulfonyl]-l.2-dipheny]-l,2-ethanediaminc also furnishes <7 t/-/(-hydroxy esters with high induced stereoselectivity64. For this purpose, the bromide generated from 10 and tribromoborane is reacted with tm-butyl propanoate in the presence of triethylamine to deliver the (A )-enolate. The subsequent addition to aldehydes gives predominantly tOT/ -/)-hydroxy esters (anti/syn 94 6 to 99 1) of 75 to 97 % ee. The diastereose-lectivity can be improved when, instead of /erf-butyl propionate, the corresponding ( + )-men-thyl ester is used64. 

For the determination of the enantiomeric excess. 23 mg of the mi-hydroxy ester (containing 2 5% //-product) and 9 mg of tris[3-(heptafluoropropylhydroxymethylene)-a-camphorato]europium are dissolved in 0.5 mL of CDC13. The ec is calculated from the peak heights and areas of the resolved doublets, due to the methyl groups attached to C-2. of the minor (f) 1.74) and major (<5 1.98) enantiomers. 

A large excess of 1,2-ethanediol (threefold) is reacted with adipic acid until carboxyl groups have reacted. The excess of 1,2-ethanediol is distilled off under vacuum in the presence of Ti(OBu)4 as hydroxy-ester interchange catalyst. The reaction can be followed by SEC analysis of samples withdrawn from reaction medium and stopped when the desired molar mass has been reached (Scheme 2.48). 

The dimethyl ester of a carboxy-terminated diamide is reacted with 1,2-ethanediol in the conditions of PBT synthesis. The amide functions are unaffected while the hydroxy-ester interchange reaction proceeds to the formation of an alternating copolyesteramide (Scheme 2.60). The procedures given below are reproduced from ref. 430. (Copyright 1997 Elsevier Science Ltd, with permission of the copyright owner.)... 

Another important class of pharmaceuticals which is prepared from chiral 2-hydroxy acids is the angiotensin-converting enzyme (ACE) inhibitors. (R)-3-phenylpropionaldehyde cyanohydrin is transformed into the corresponding 2-hydroxy ester which after activation by sulfonylafion reacts with dipetides to give, under inversion of configuration, ACE inhibitors known as prils (Scheme 6). ... 

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