Tetrahydropyranyl derivatives

D-(l-2H)Glucopyranose was prepared (170) by direct reduction of D-glu-cono-1,5-lactone, in deuterium oxide solution, with sodium amalgam in the presence of phosphoric acid-rf3, or, alternatively, by reduction of the lactone tetrahydropyranyl derivative with sodium borodeuteride in tetrahydrofuran (171). 

In a clever adaptation of the acid-catalyzed addition of />-quinone ketals to olefins Buchi and Chu condensed 586 with 1,2-dimethylcyclopentene in the presents of stannic chloride and inun ately reduce the two diastereomeric adducts with sodium borohydride The major alcohol 587 was separated, catalytically hydrogenated, and converted to the tetrahydropyranyl derivative 588 (Scheme XLVII). 

South described the protection of 4,5-dichloropyridazin-3(2//)-one as a 2-tetrahydropyranyl derivative. The pyr-idazinone is treated with 3,4-dihydro-2/7-pyran in the presence of /)-toluenesulfonic acid or pyridinium -toluene-sulfonate in refluxing tetrahydrofuran <1995JHC1473>. The deprotection is discussed in Section 8.01.8.1. 

Adrenolactone (3). A new synthesis of the lactone involves reaction of the tetrahydropyranyl derivative of 3/ -hydroxy-17-ketoandrostene (2) with the dilithio derivative of 1. 

Some heterocycles can be linked to supports as tetrahydropyranyl derivatives. Attachment of indoles, purines, or tetrazoles (Table 3.29) has been achieved by treatment of a support-bound dihydropyran with the heterocycle in the presence of catalytic amounts of pyridinium tosylate [487], camphorsulfonic acid [539], or TFA [540] in DCE at 60-80 °C for 16-24 h. Indole-derived orthoesters, such as that in Entry 7 (Table 3.29), can be prepared by heating the indole with triethyl orthoformate (160 °C, 24 h) followed by acid-catalyzed reaction of the resulting orthoester with a resin-bound diol [541,542], As illustrated by Entry 8 (Table 3.29), indoles can also be linked to the Wang resin or related supports as carbamates. Cleavage by TFA is, how-... 

Perhaps the strongest support for the argument, that enhancement of cardiotonic activity by the carbohydrate component is a function of hydroxylation, may be gained by inspection of the potencies of the completely deoxygenated 3-tetrahydropyranyl derivatives of digitoxigenin (1) and of strophanthidin (2) (see Table I). In each case, the value ob-... 

Nuclear motions in the tetrahydropyranyl ring of a tetrahydropyranyl derivative, consequent upon departure of an axial and of an equatorial leaving group... 

Reduction of 2,2-dimethyl-cyclohexane-1,3-dione (50) with Baker s yeast gave alcohol (ee 98.3%) whose tetrahydropyranyl derivative on methoxycarbonylation produced (51) quantitatively. Michael addition of (51) with methyl vinyl ketone followed by heating the adduct under reflux with pyrrolidine in benzene yielded (52) in 85% yield as stereoisomeric mixture whose separation presented problems. In order to eliminate the complexity due to a chiral center in tetrahydropyranyl protective group, deprotection of (52) was achieved by treatment with p-toluenesulphonic acid in methanol. The product obtained was a mixture of the lactone (53) and hydroxy ester (54). Probably the stereoisomer of... 

A similar reaction occurs when enol ethers react with alcohols in acid solution and in the absence of water, but now we are starting in the middle of the acetal hydrolysis mechanism and going the other way, in the direction of the acetal A useful example is the formation of THP (= TetraHydroPyranyl) derivatives of alcohols from the enol ether dihydropyran. You will see THP derivatives of alcohols being used as protecting groups in Chapter 24. 

The preparation of the tetrahydropyranyl derivative of propargyl alcohol is a modification of a published3 general procedure that is simple and useful for large-scale preparations. 

The first part of the procedure illustrates a method for the preparation of the tetrahydropyranyl derivative of an alcohol which requires no extraction or wash procedures during the workup of the product. 

Distillation of the residue after the first treatment with Dowex 50 and methanol gives a product containing 7-10% of the tetrahydropyranyl derivative of methyl 4-hydroxy-2-butynoate. Removal of the by-product 2-methoxytetrahydropyran and retreatment with Dowex 50 and methanol give a product containing only 0.5-1.5% of the undeblocked alcohol. 

Somewhat more difficult is the pharmacological evaluation of 18-tetrahydropyranyl derivatives (XXX) and of 18-sulfides of methyl reserpate or methyl 18-epireserpate (XXXI). In general, the tetra-hydropyranyl ethers and their analogs show both sedative and antihypertensive activity, albeit in a reduced way. It seems that the... 

Selective iV-demethylation of each amino sugar in spiramycin allowed synthesis of a variety of A-acyl derivatives [66]. Hydrolysis of the more acid-labile neutral sugar (mycarose) yields the corresponding neospiramycin factors [67], while further hydrolysis of forosamine yields the forocidin factors [68]. Several 4 -deoxy and 4 -0-tetrahydropyranyl derivatives of neospiramycin I have been synthesized, but although some of these had activity comparable to spiramycin, none demonstrated enough significantly superior properties to justify clinical studies [69, 70]. 

Propargylic alcohols, even though tertiary (1), react with dihydropyrane under catalysis from p-toluenesulfonic acid to give tetrahydropyranyl derivatives (2), which are stable to base but hydrolyzed readily by aqueous acid or magnesium sulfate. ... 

Electrophilic catalysis of the departure of halogens in the century-old Koenigs-Knorr reaction is implicit in the use of heavy metal bases such as silver oxide and mercuric cyanide, but the first demonstration of electrophilic catalysis in water (in the hydrolysis of the p-glucoside of 8-hydroxyquinoline by first-row transition metals (Cu Np > C")) was by Clark and Hay in 1973. The observations were expanded to the more conveniently followed (because more labile) benzaldehyde methylacetals or tetrahydropyranyl derivatives of 8-hydroxyquinoline, whose hydrolysis is now known to give solvent-equilibrated oxocarbenium ions (Figure 3.19). Surprisingly, however, the observation of electrophilic catalysis of glycoside hydrolysis itself was not picked up by paper... 

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