The Quercitols

Power and Tutin,244 its identity was not established until years later.246 (—)-Vibumitol has also been found in Stephania hemandifolia, an Australian plant,247 and in Menispermum canadense.l46 

Other quercitols have been synthesized by catalytic hydrogenolysis of the corresponding inososes (see p. 180). All the known quercitols are shown, with their names, in formulas CXXXIX-CXLIV according to Angyal and Macdonald s proposals,6 the quercitol of acorn is called (+)-profo-quercitol, and natural viburnitol is named (—)-w 6o-quercitol the corresponding Fletcher-Anderson-Lardy names are (+)-1 -deoxy-mwco-inositol and ( —)-1-deoxy-WM/o-inositol. Synthesis of the four as-yet-unknown diastereomers should not present serious difficulties. 

Finally, the enantiomorph, (+)-rf6o-quercitol, was synthesized248 by hydrogenation of the corresponding inosose in acid solution (XCIV — XCV see p. 180). 

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Synthesis of Deoxyinosamines from vibo-Quercitol. As yet, the quercitols have rarely been used as synthetic starting materials. Recently, however, Suami and Yabe (42) have reported clever syntheses of two (acetylated) deoxyinosamines (8 and 9, Y= NHAc) and one (acety-lated) deoxyinosadiamine (10, Y = NHAc) from racemic vibo-quercitol... 

The discoverer of levorotatory proto-quercitol unfortunately described it (36) as L-quercitol. The capital letter l should of course be understood to designate configuration, not rotation. And according to one widely accepted convention (18,19), the quercitol stereosiomer which has the configuration 13 would be designated V , not l . (See formulas 12 and 13.) The name quercitol is now used in a generic sense (cyclo-hexanepentol), so that there are actually six diastereomers to which the name L-quercitol might apply. 

In early experiments, the pentamethyl ether (18) was treated with phosphorus pentachloride in the hope of obtaining a chloropentol reducible to ( — )-proto-quercitol. (Allowing for the benzoyl migration, the expected product would have been (— )-uibo-quercitol (11).) Surprisingly, the quercitol actually obtained after demethylation and dehalogena-tion was neither of these but still another previously known isomer, meso-scyllo-quercitol (24) (27). 

It is now reported by P. Szabo that the quercitols can be titrated with completely normal results, by using suitable experimental conditions, and especially low temperature and low pH, for the titrations (40,41). This method might also be applicable to the estimation of the tetrols. 

The present review is to be regarded as a continuation of Fletcher s article1 the facts described therein will not be repeated here unless required for the understanding of recent developments. Because of the considerable expansion of cyclitol chemistry, it is not practicable to cover, as Fletcher did, all compounds of the cyclitol group. Only the inositols, the quercitols, and the inosamines, their derivatives, and some closely related compounds will be discussed the tetrahydroxycyclo-hexanes and -hexenes, and quinic and shikimic acids—on which subjects many important papers have appeared—are not reviewed here.3... 

According to the Angyal proposals, the cyclohexanepenfo/s are all called quercitols, and these compounds, like the pentahydroxycyclohexanones inososes), are differentiated by trivial prefixes, the same prefix being used for the quercitol and the inosose of the same configuration. These prefixes are shown under the formulas CXXXIX-CXLIV (see p. 190). In the Fletcher-Anderson-Lardy system, these compounds are named as deoxy and keto derivatives, respectively, of inositols. The Angyal names will be... 

An interesting transition from the inositol to the quercitol series has recently been accomplished by Posternak. While hydrogenation of scyllo-meso-inosose with platinum oxide as a catalyst in neutral solution gave the expected mixture of meso-inositol and scyllitol, it was found that, when the reduction was carried out in dilute sulfuric acid solution, two moles of hydrogen rather than one were consumed and the product was a desoxyinositol, presumably the symmetrical form XLIX. That this reaction does not proceed through an inositol is shown by the stability of mcso-inositol under the conditions of the experiment. 

Well known alternatives to this fractional notation are based on the use of a set of eight prefixes alio, cis, dl, epi, muco, myo, neo, and scyllo) for the inositol configurations, and of ten prefixes alio, cis, epi, gala, muco, neo, proto, scyllo, talo, and vibo) for the quercitol configurations. Since these nomenclatures, due mainly to Fletcher, Anderson and Lardy, and... 

The quercitols (cyclohexanepentols) are less important than the inositols. All the stereoisomers predicted by theory are now known but only two of them were found in Nature (-i-)- 0to-quercitol (IX) originally named querdtol , in the acom and several other sources, and (—)-vi6o-quercitol (X) first named /evo-rotatory querdtol and later vibnmitol . in several plants. Other quercitols have been made by catal3dic hydrogenation of inososes in acid solution. 

The deoxyinositols (quercitols, cyclohexanepentols) are useful model compounds which display many of the physical and chemical properties of true deoxy sugars. Although (-b)-proto-quercitol, the best known isomer, was isolated from nature 118 years ago, no synthesis has been reported up until now. The synthesis here described is actually that of the (-)-enantiomer, starting with (-)-inositol however, identical procedures applied to the readily available ( + ) or dl-inositol would give (- -) or DL-proto-quercitol, respectively. The natural occurence of, )-proto-quercitol has... 

The vibo or dl (124/35) quercitol (4) needed for the synthesis was prepared from rat/o-inositol (2) via the bromoquercitol (3) according to the method of McCasland and Horswill, (28). By acetonation, acetylation, deacetonation, and equatorial mesylation the mesyloxy derivative... 

Natural Occurrence of ( — )-proto-Quercitol. Although the dextrorotatory form (12) of proto-quercitol was discovered in acorns more than a century ago by Braconnot (5), who at first thought that it was lactose, the levorotatory form (13) remained unknown until 1961. In that year, Plouvier isolated it from leaves of the tree Eucalyptus populnea the yield was 0.55% (36). The optical rotation of the new compound was equal and opposite to that of the dextro enantiomer, and it was identical to the latter in its crystal form, melting point, solubilities, molecular formula and infrared spectrum. 

Plouvier then prepared the previously unknown racemic form of proto-quercitol by mixing equal weights of the two enantiomers. The melting point (237°C.) of the mixture was not depressed, and its (presumably solid state) infrared spectrum reportedly (36) was identical with that of either active form. It thus appears that DL-proto-quercitol exists as a solid solution, not a racemic compound or conglomerate. 

According to the modified Maquenne system (18,19,31) used in this chapter, the diastereomeric configuration of any cyclitol is expressed by a fraction, and position-numbering, if otherwise equivocal, is so assigned that the numerator will have the lowest possible numbers. For example, proto-quercitol (12 or 13) is designated (134/25,), not (14/ 235) or (25/134). 

The Synthesis of (— -proto-Quercitol, Although proto-quercitol (dextro) was discovered in 1849 ( 5), its cyclohexanepentol structure was not established until 1885 (13), and its configuration not until 1932. (38). The synthesis of this well-known cyclitol has been a difficult problem, since it appears that nearly every synthetic reaction commonly employed for other cyclitols would lead stereospecifically to the wrong product. 

It was not until 1966 that the synthesis of proto-quercitol (levo) was finally accomplished (30) by indirect removal of the position 2 hydroxyl group in (—) -inositol (14). 

The pure, crystalline (— )-proto-quercitol (13) which was isolated had an infrared spectrum identical with that of authentic ( + )-proto-quercitol, and its optical rotation was equal and opposite. Further characterization and preparation of the racemic form, by mixing the enantiomers, is described elsewhere (30). 

The identical synthetic procedures applied to ( + )-inositol or dl-inositol should lead to ( + )-proto-quercitol and DL-proto-quercitol, respectively. Since the total synthesis of DL-inositol had previously been reported (33), the new syntheses of the various forms of proto-quercitol are total, with the possible exception of the step for resolution of DL-inositol, which so far has been accomplished only by a microbiological method (43). 

Early in 1961, the first successful use of NMR for the assignment (22) of configuration to a quercitol (26) was accomplished indirectly, by analysis of the spectrum of its 6-bromo derivative. The spectrum of this bromoquercitol (25 or 28) fortunately contained a well-resolved AB... 

In the past, periodate titrations have been of limited value for establishing the structure of quercitols or cyclohexanetetrols. The former show overoxidation, because of the fact that malonaldehyde is formed, and this compound undergoes further oxidation. Some isomers of the tetrols... 

Thus, as far as ( + )-quercitol is concerned (Figure 5), the time curves show that a small quantity of malonaldehyde is liberated at the beginning... 

Figure 5. Periodate uptake (10f) and malonaldehyde formation (MA) during the oxidation of (+)-quercitol with sodium metaperiodate (c.f. Table I).

No hypotheses can be advanced for the sequences involved in the oxidation of cyclohexanepentols which react even more slowly with periodate than does (+)-quercitol. For instance, when the all-trans l 3, 5/2, 4-cyclohexanepentol (33) is oxidized (Figure 6), production of malonaldehyde starts very early and the time curve of periodate reduction indicates a very complex reaction. Nor is it possible to analyze satisfactorily the curves obtained with (1 l)-1, 2, 4/3, 5-cyclohexane-pentol (34) or with dl-1, 2, 3, 4/5-cyclohexanepentol (35) [this is the configuration predicted for the (1 D)-entantiomorph (41)]. 

Viscum album L. subsp. coloratum Kom. V. album L. subsp. coloratum Kom. f. rubroaurantiacum (Makino) Kitag. V. coloratum (Kom.) Nakai Hu Ji Shang (Asiatic mistletoe) (leaf, stem) Oleanolic acid, beta-amyrin, fatty acids, mesoinositol, flavoyadorinin, homoflavoyadorinin, lupeol, myristic acid, agglutinins, alkaloids, quercitol, querbrachitol, quencetine, acetylcholine, choline, histamine, tyramine, vitamins E and C.33-450 Antihypertensive, prolong the life of patients with late stage stomach cancer. 

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