Quercitol proto

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... 

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. 

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. 

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). 

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). 

Figure 2. Proton magnetic resonance spectra at 14.1, 23.5, and 51.7 kilogauss (60, 100 and 220 MHz.) of (H-j-proto-quercitol in deuterium oxide.

Malonaldehyde has been identified by Fleury and coworkers as a product of the rapid stage of the oxidation of (+)-proto-quercitol. 79 It is slowly oxidized, with the consumption of another four moles of periodate per mole, to formic acid and carbon dioxide. 

Salamci, E., Secen, H., Siitbeyaz, Y. and Bald, M. (1997) A condse and convenient synthesis of dl-proto-quercitol and dl-golo-quercitol via ene reaction of singlet oxygen combined with [2 + 4] cycloaddition to cyclohexadiene. Journal of Organic Chemistry, 62 (8), 2453-2457. 

Early efforts to use p.m.r. spectroscopy to establish the configurations of diastereoisomeric quercitols were unsuccessful, with two exceptions,64 because of complex spin-spin coupling, and overlapping of multiplets at 60 and 100 MHz. However, in the p.m.r. spectrum of (-l-)-proto-quercitol (7) in deuterium oxide at 220 MHz (see Fig. 1),... 

Salamci, E., Secen, H., Sutbeyaz, Y., Balci, M., A Concise and Convenient Synthesis of dl proto Quercitol and dl gala Quercitol via Ene Reaction of Singlet Oxygen Combined with [2 + 4] Cycloaddition to Cyclohexadiene, J. Org. Chem. 1997, 62, 2453 2457. 

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... 

Although proto-quercitol was isolated " from botanical sources in 1849, and wbo-quercitoP in 1904, the configurations were not established until 1932, and 1950, respectively. ... 

As yet, only the (+)-proplant species from eight other botanical families also contain profo-querci-tol. ... 

Pentaacetates are the most used quercitol derivatives (see Table I). Proto- and i)i6o-quercitol readily form isopropylidene acetals the all-equatorial scyUo isomer does not. The remaining isomers would presumably give such acetals, or in some cases, di-O-isopropylidene acetals. 

Mild oxidation of quercitols gives ketotetrols (or, occasionally, diketo-triols), and is achieved by the use of Acetobacter suhoxydans, - - catalytic oxygenation, or a halogen. Catalytic oxidation of mwco-quercitol is the first step in a reported synthesis of the antibiotic degradation product, 2-deoxystreptamine (better named 5-deoxystreptamine). Acetobacter studies on the cis, neo, proto, scyllo, and vibo isomers have been reported. Most halogen-oxidation products have not been well characterized. 

In 1908, Kubler, by the action of hypobromous acid on natural con-duritol (32), obtained two bromoquercitols, probably having the configurations dl(134/256) and dl(125/346), (13 and 39). The former isomer should yield the unknown DL-proto-quercitol on dehalogenation the latter isomer (m.p. 196°) was poorly characterized, but it quite possibly was identical with an isomer of m.p. 192° since prepared by Nakajima and Kurihara (see Table III). 

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