Cyclic monoacetates

The synthetic utility of the above transformations stems from the fact that many monoesters obtained as a result of hydrolysis may be converted to pharmaceutically important intermediates. For example, the optically active glycerol derivative (27) is a key intermediate in the production of p-blockers. Allyl derivative (25) may be converted into (3)-paraconic acid [4694-66-0] ((JT)-5-oxo-3-tetrahydrofurancarboxylic acid) that is a starting material for the synthesis of (3R)-A-factor. The unsaturated chiral cyclic monoacetate (31) is an optically active synthon for prostaglandins, and the monoester (29) is used for the synthesis of platelet activating factor (PAF) antagonists. 

Cyclic monoacetates of Table 11.1-3, which can be obtained with other hydrolases as such or of opposite configuration, are contained in Tables 11.1-9, 11.1-11 and 11.1-18. 

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). 

Diol monoacetates are obtained from the diols via the intermediate formation of the bromomethyl acetals and their conversion into cyclic methylene acetals, which undergo acid-catalysed ring-opening to yield the acetate ester [31]. The ring-opening is regio-specific to form the ester at the least hindered hydroxyl group. 

One-pot conversion of bromomethyl cyclic acetals into diol monoacetates... 

Various cyclic compounds from three-membered rings to macrocycles have been prepared by intramolecular allylation. A typical example of this cyclization is the reaction of the monoacetate of 1,4-butenediol derivative 91 with the active methylene compound 92, which afforded the allylic alcohol 93. The three-membered chrysantemic acid derivatives 94 and 95 were then prepared after acetylation of 93, followed by Pd-catalysed intramolecular allylation [53],... 

Acid Catalyst. Camphorsulfonic acid (CS A) has been used extensively in synthetic organic chemistry as an acid catalyst. It has particularly been used in protecting group chemistry. For example, hydroxyl groups can be protected as tetrahydropyranyl (THP) ethers using dihydropyran and a catalytic amount of CSA (eq 1). Both 1,2- and 1,3-diols can be selectively protected by reaction with orthoesters in the presence of camphorsulfonic acid to form the corresponding cyclic orthoester (eq 2) This method of protection is particularly useful in that reduction of the orthoester with Diisobutylaluminum Hydride forms the monoacetal, which allows for preferential protection of a secondary alcohol in the presence of a primary alcohol. Ketones have also been protected using catalytic CSA (eq 3). ... 

Mass spectrometry has proved to be a useful complement to other methods for elucidating the structure of cyclic acetals. The reader is referred to several excellent reviews on the mass spectrometry of carbohydrates that have appeared within the time span covered by this article.65a 65<1,66 Mass spectrometry is a valuable aid for distinguishing pyranose from furanose structures, and monoacetals from diacetals. It may also facilitate the assignment of ring location. However, it is generally insensitive to configurational differences. 

Table 11.1-8. Acetylcholine esterase-catalyzed enantiotopos-differentiating hydrolysis of prochiral cyclic diol diacetates and of racemic monoacetates in aqueous solution.

A sensitive method for the detection and separation of micro quantities of cyclic acetals of sugars by means of gas-liquid, partition chromatography has been described by Jones and coworkers. The column packing consisted of an intimate mixture of Apiezon M grease on Cromosorb W and butanediol succinate polyester on Cromosorb W, which was packed on top of a column of SE-30 methylsilicone polymer and glass beads. The column temperatme was maintained at 200°. Some cyclic acetals of sugars have been fractionated by gas-liquid chromatography as their (trimethyl-silyl) ethers. These derivatives are conveniently prepared and the method is especially suited to the less volatile monoacetals. 

Another experimental result is also consistent with the hypothesis that cyclic 1,2,3-triketones are not stable. 2-Diazoindan-l,3-dione (9.91) is oxidized by eA butyl hypochlorite in ethanol to the 2-monoacetal 9.92 of indan-l,2,3-trione. The monoacetal undergoes hydrolysis to 2,2-dihydroxyindan-l,3-dione (ninhydrin hydrate 9.93), but the trione itself could not be identified (9-41). 

Treating diethyl (-h )-(i ,i )-tartrate (lb) with triethyl orthoacetate under acidic conditions provides the cyclic orthoester 530, which is then ring opened with acid to afford the monoacetate 531 in 94% overall yield. Protection of the free hydroxyl group followed by basic hydrolysis of the acetate furnishes 532. The regioselective reduction of 532 with borane-dimethylsulfide complex and a catalytic amount of sodium borohydride followed by acetonide... 

The middle part is always a conjugated polyene (symmetrical or unsymmetrical) and can be prepared by a number of established methods which are discussed in detail in Chapter 3 Part I. Some of these middle parts are readily available more common ones, e.g. the Cio-dialdehyde, are manufactured on a ton scale as industrial intermediates for the technical syntheses of (3,(3-carotene (3) and astaxanthin (406). For the synthesis of unsymmetrical carotenoids, the Cio-dialdehyde can be converted into a monoacetal derivative. The free aldehyde moiety is coupled with one end group, and the intermediate product is deprotected and then combined with the second end group. In these reactions, there are some positions which permit a coupling in high yield [C(9)-C(10) and C(11)-C(12)] and others [C(7)-C(8)] which, for cyclic carotenoids, give products in only low yield because of steric hindrance due to the adjacent methyl groups. The choice of the middle part and its synthesis has become a simple matter today. 

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