Ethers and glycosides

Ethers (R-O-R) are frequently found as natural products in nature. The most common ether is that of methanol and the phenolic hydroxyl group. The methyl ether (methoxyl group) is very stable and therefore not reactive. Shown below is the formation of methoxybenzene (2.30) from phenol and methanol. 

Glycosides - formed between a sugar molecule and an alcohol - are in some sense similar to ethers. Glycosides are formed between the sugar molecule in a ring conformation (pyranose or furanose form) and an alcohol. The example below shows D-glucose (2.31), in equilibrium with p-D-glucopyranose (2.32). 

In presence of acid, cation 2.33 reacts with phenol (2.5) to result in a mixture of the a- and P-glucoside (2.34 and 2.35, respectively). Chemically this reaction involves the formation of an acetal (2.34 and 2.35) from a semiacetal (the pyranose 2.32 the furanose could also react). Unlike typical ether bonds, the glycoside bond is susceptible to acid hydrolysis. 

---

The reaction conditions applied are usually heating the amine with a slight excess of aldehyde and a considerable.excess of 2d-30hydrochloric acid at 100 °C for a few hours, but much milder ( physiological ) conditions can be used with good success. Diols, olefinic double bonds, enol ethers, and glycosidic bonds survive a Pictet-Spengler reaction very well, since phenol and indole systems are much more reactive than any of these acid sensitive functional groups (W.M. Whaley, 1951 J.E.D. Barton, 1965 A.R. Battersby, 1969). 

Ulubelen A, Kerr KM, Mabry TJ. (1980) New 6-hydroxyflavonoids and their methyl ethers and glycosides from Neurolaena oaxacana. Phytochemistry 19 1761-1766. 

Three types of carbon-oxygen linkages may occur in a polyuronide ester, ether and glycoside. The ester-linked methyl group of pectins is split by cold dilute alkali. It may also be removed by certain enzymes. Methyl groups which often occur ether-linked to the uronic acid especially in plant gums and hemicelluloses, resist hydrolysis by mineral acid solutions of 2 to 4% concentrations, even in the autoclave. Such groups survive hydrolytic conditions that are usually chosen. 

Lock has investigated the photosensitized oxidation of ethers and glycosides and has found that, in addition to the mode of oxidation repre-... 

The photodegradation of W-alkyl amides (as simple models for the nylon molecule) was examined there is a close similarity in their behavior to that of alcohols, ethers, and glycosides. A comparison is given in the following equations. 

Interestingly, particularly in view of the relatively minor effect of silyl ethers and glycosidic bonds at 02, the 4,6-O-benzyIidene directed p-mannosylation reaction is highly sensitive to steric bulk in the protecting group for 03 [118]. Thus, a 2-O-benzyl-3-O-TBDMS protected draior was found to be considerably less selective than the 3-0-benzyl-2-0-TBDMS regioisomer toward a common acceptor (Scheme 24) [19, 118],... 

Flavonoids are characterized by having an aromatic ring with different degrees of substitution, including functional derivatives such as esters, methyl ethers, and glycosides. These structural characteristics determine the general physicochemical properties of these compounds. 

Derivatives. Many derivatives of acylated phlorogluciaols that bear a benzene ring substituent or an ether or glycoside linkage occur ia aature. Examples are cotoia [479-21-0] (52) ia coto bark and conglomerone [480-25-1] (53) ia Eucalyptus conglomerata. 

BBr is a very useful reagent for cleaving ethers, esters, lactones, acetals, and glycosidic bonds it is used to deoxygenate sulfoxides and in the preparation of image-providing materials for photography (5). 

In this Section, ether and acetal substituents will be discussed. In some polysaccharides, the terminal reducing sugar is glycosidically linked to a non-sugar aglycon, and this will be discussed in a special part. 

In carbohydrate chemistry, the preparation of ethers that are stable in the presence of acids, bases, and aqueous alkali is an important analytical and synthetic tool. The methods used for the etherification of hydroxyl groups51 generally employ reactions of unprotected sugars and glycosides with methyl, allyl, benzyl, triphenylmethyl, and alkylsilyl halides in the presence of a variety of aqueous and nonaqueous bases. 

This class of donor is activated by soft Lewis acids, such as copper triflate at room temperature, and despite their hydrolytic instability, they appear inert to conditions of sulfoxide activation, TMSOTf or Tf20 (Scheme 4.53). Activation is achieved with stoichiometric promoter in the presence of the acceptor alcohol, and although the mechanism has not been investigated, presumably it proceeds via coordination followed by collapse to a stabilized oxacarbenium ion. The method is compatible with standard glycosidation solvents such as dichloromethane, acetonitrile and diethyl ether, and ester-directed couplings do not lead to orthoesters, perhaps as a result of the presence of the Lewis acid promoter [303,304]. 

This report deals with the synthesis and biological evaluations concerning photodynamic therapy properties of porphyrinyl- and dihydroporphyrinyl-type sugar derivatives. The chosen conjugates have O- and >S-glycosidic moieties or ether and ester functions. 

This review deals with the synthesis of porphyrinyl-type sugar conjugates developed and biologically accessed, and considers the involvement of macrocycles of the porphyrin and chlorin (dihydroporphyrin) types, with O- and 5-glycosides or ether and ester functions. 

An interesting linker is based on bis(4-hydroxyphenyl)disulfide 3 (Scheme 9.9). Both MPEG and the carbohydrate are linked as ethers, and for removal from MPEG, the linker s disulfide bond is reductively split by propanedithiol. The carbohydrate is freed as a glycoside of 4-hydroxyphenylmercaptan.38... 

Shinoda, K., Yamanaka, T., andKinoshita, K. Surface chemical properties in aqueous solutions of non-ionic surfactants octyl glycol ether, a-octyl glyceryl ether and octyl glycoside. J. Phys. Chem., 63(5) 648-650,1959. 

Scheme 3.—Proposed Mechanism for the Photochemical Cleavage of 2-Nitrobenzyl Ethers and 2-Nitrobenzyl Glycosides.

---