Acetal derivatives synthesis

Okamoto, Y. and Sakurai, H., Preparation of (dialkoxyphosphinyl)-methyl-substituted ketone alkyl trimethylsilyl acetal derivatives, Synthesis, 497, 1982. 

Fluorophenylalanine acts in a manner different from other inhibitors, since it permits protein synthesis. This difference in behavior results in incorporation into proteins (Westhead and Boyer, 1%1) that often possess decreased or altered activity (G and Millard, 1971). Further studies showed that the addition of fluorophenylalanine caused extensive inhibition of fatty acid and phenol (acetate-derived) synthesis shortly after administration (Ward and Packter, 1974), presumably after incorporation into the polypeptides comprising fatty acid synthetase. In contrast, cycloheximide halved... 

A recent synthesis of P-D lactone (Scheme 13.51) used an enantioselective catalytic approach. A conjugate addition of a silyl ketene acetal derived from an unsaturated ester gave an unsaturated lactone intermediate. The catalyst is CuF-(S )-tol-BINAP.30 The catalytic cycle for the reaction is shown below. 

The synthesis of Baccatin HI shown in Scheme 13.57, which was completed by a group led by the Japanese chemist Teruaki Mukaiyama, takes a different approach for the previous syntheses. Much of the stereochemistry was built into the B-ring by a series of acyclic aldol additions in Steps A through D. A silyl ketene acetal derivative... 

These acid-catalyzed C-glycosylations were successfully extended to the D-ribofuranose series by Sorm and coworkers,148 who utilized the reaction in the first reported synthesis of showdomycin. Thus, treatment of 2,3,5-tri-0-benzoyl-/3-D-ribofuranosyl bromide (81) with 1,2,5-trimethoxybenzene in the presence of zinc oxide gave 2,4,6-trimethoxy-l-(2,3,5-tri-0-benzoyl-/3-D-ribofuranosyl)benzene (196). Ozonolysis of the corresponding acetate derivative, followed by esterification, gave the highly functionalized C-/3-I>ribofuranosyl derivative (197), which was used as a key intermediate in the synthesis of showdomycin (see Section III,l,b). 

Reactions of acetal derivatives of aldonolactones involving the lactone carbonyl group or used as chiral precursors in the synthesis of noncarbohydrate natural products are discussed in later sections. 

The protective method has also been employed with 3-ketoesters. In this case, the goal is to avoid keto-enol photoisomerization that is an efficient energy-wasting channel. Scheme 74 shows that direct photorearrangement of aryl benzoyl acetates (298) to the ort/jo-hydroxydibenzoylmethanes (299) is poor, whereas irradiation of the related acetal derivatives gives higher yields [208]. The resulting ort/ o-hydroxydibenzoylmethanes are precursors for the synthesis of flavones. Related flavonoids can be obtained in similar yields by PFR of aryl dihydrocinna-mates [209]. 

The synthesis of oxygen- and nitrogen-containing heterocyclic compounds by anionic cyclization of unsaturated organolithium compounds has been reviewed recently. " Broka and Shen reported the first intramolecular reaction of an unstabilized a-amino-organolithium compound using reductive lithiation of an A,5-acetal derived from a homoaUylic secondary amine (Scheme 21). Just one example was reported treatment with lithium naphthalenide gave the pyrrolidine product, predominantly as the cis isomer. 

Aminopyrans 244, spiro-conjugated with an polycyclic N,0,S-system, have been synthesized using N,S-acetal derivatives of actylacetone and acetoacetic ester 245 (00PS(160)105). Diacetyl derivative 245 (Z = COMe) undergoes deacetylation in the course of pyran synthesis (Scheme 93). 

Apart from 1,3,4-oxadiazole (b.p. 150°C), its lower alkyl derivatives and some dihydro compounds, 1,3,4-oxadiazoles are generally solids. In synthesis, the common method of purification is by crystallization of the crude reaction product. A few oxadiazoles, for example, alkyl ethers and acetates derived from 2,5-dihydro-2-hydroxy-2,5,5-trialkyl-l,3,4-oxadiazoles (cf. (38)), have been purified by distillation under reduced pressure. In some cases, chromatography over silica gel has been used. 

The direct carbonylation of methanol yielding acetic acid, the Monsanto process, represents the best route for acetic acid. Carbonylation of methyl acetate, obtained from methanol and acetic acid, gives acetic anhydride, a technology commercialized by Tennessee Eastman (22). It is noteworthy that this process is based on coal derived synthesis gas to give as the final product cellulose acetate. A combination of Monsanto and Tennessee Eastman technology opens the door for the combined synthesis of acetic acid and acetic anhydride. 

Synthesis The reaction of benzothiazolo-3(2H)-one-1,1-dioxide with methyl chloroacetate gives the methyl 2(3H) acetate derivative, which is isomerized with sodium methoxide in toluene/terf-butanol yielding methyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate-1,1 -dioxide. The subsequent methylation with methyl iodide in methanol yields the 2-methyl compound. Finally this compound is treated with 2-amino-5-methylthiazole in xylene (Trummlitz et al. (Thomae GmbH), 1979 Trummlitz et al., 1989 Kleemann et al., 1999). 

The aldol reaction between a chiral a-amino aldehyde 16 and an acetate derived enolate 17 creates a new stereogenic center and two possible diastereomers. Several different methods for the synthesis of statine derivatives following an aldol reaction have been reported most of them lead to a mixture of the (35,45)- and (3/ ,45)-diastereomers 18 (Scheme 3), which have to be separated by laborious chromatographic methods.[17 211 Two distinct approaches for stereochemical control have been used substrate control and reagent control. 

Polyketides.1 Polyketides are useful as precursors to acetate-derived natural products, but they are unstable owing to a marked tendency to undergo internal condensation. A new synthesis involves ozonolysis of products of Birch reduction. An example is the synthesis of the polyketide 3 from the aromatic system 1. 

This variation was used for an enantioselective synthesis of anti-a-methyl-p-hydroxy esters using the silylketene acetal derived from (1R, 2S)-N-methylephed-rine-O-propionate (equation II).12... 

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