Cyclitole

Cyclitols as novel chiral building blocks in synthesis of heterocyclic natural products 97CC807. 

The syntheses were effected by selective mesylation of one or two hydroxyl groups and displacement of each mesyloxy group by an azido group, which was reduced to amino. Although attempted SN2 displacement of cyclohexane substituents is often unsuccessful, the powerfully nucleophilic azide ion is usually able to displace an alkylsulfonoxy group, and this route has been exploited in several recent cyclitol syntheses. 

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). 

Until some uniform configurational nomenclature for cyclitols has been generally accepted, it would appear safer for authors in this field to specify the nomenclature used in every article, or to indicate configurations by means of formulas. 

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. 

Cyclitol Spectra at 220 MHz with the Superconducting Solenoid. In 1964, Nelson and Weaver (34) at Varian Associates constructed a superconducting solenoid with which proton spectra can be observed at 51.7 kilogauss (220 MHz.) or even higher fields. Other nuclei have been observed at suitable field/frequency combinations. 

The power of the new spectrometer to reveal configurations of difficult cyclitols or sugars was first tested with mt/o-inositol (2), using deuterium oxide as solvent. At 60 or 100 MHz. the one equatorial and five axial protons appear to have different chemical shifts as shown by Lemieux in 1956 with a 40 MHz. instrument (14,15). However, since the five-proton axial signal could not be resolved, one could probably not have assigned the configuration 2 (which was already known from laborious chemical correlations extending over many years.)... 

With the new very high resolution NMR spectra, it should be a simple matter to assign configurations to other difficult cyclitols or carbohydrates, for example, the numerous still undiscovered isomers of 6-bromo, 6-chloro, and 6-iodoquercitol (20 diastereomers predicted for each). 

The cyclitols are a group of carbocyclic sugar derivatives having the general formulation 1,2,3,4,5,6-cyclohexanehexol. How many stereoisomeric cyclitols are possible Draw them in their chair forms. 

Note. Cyclitols are generally not regarded as carbohydrates. Their nomenclature is dealt with in other recommendations [8,9],... 

Structures of this type can also be named as cyclitols [8]. 

Simple analogs of an aminoglycoside antibiotic, 2,6-dideoxy-4-0- (671) and -5-0-(2,3-dideoxy-2-fluoro-o -D-r/Z>o-hexopyranosyl)streptamine (672) were prepared by coupling of tri-O-acetyl-2-fluoro-D-glucal (666) with cyclitol derivatives 668 or 667 (through 669 and 670) as shown. 

A tandem enzymatic aldol-intramolecular Homer-Wadsworth-Emmons reaction has been used in the synthesis of a cyclitol.310 The key steps are illustrated in Scheme 8.33. The phosphonate aldehyde was condensed with dihydroxyacetone phosphate (DHAP) in water with FDP aldolase to give the aldol adduct, which cyclizes with an intramolecular Horner-Wadsworth-Emmons reaction to give the cyclo-pentene product. The one-pot reaction takes place in aqueous solution at slightly acidic (pH 6.1-6.8) conditions. The aqueous Wittig-type reaction has also been investigated in DNA-templated synthesis.311... 

Aldolases catalyze asymmetric aldol reactions via either Schiff base formation (type I aldolase) or activation by Zn2+ (type II aldolase) (Figure 1.16). The most common natural donors of aldoalses are dihydroxyacetone phosphate (DHAP), pyruvate/phosphoenolpyruvate (PEP), acetaldehyde and glycine (Figure 1.17) [71], When acetaldehyde is used as the donor, 2-deoxyribose-5-phosphate aldolases (DERAs) are able to catalyze a sequential aldol reaction to form 2,4-didexoyhexoses [72,73]. Aldolases have been used to synthesize a variety of carbohydrates and derivatives, such as azasugars, cyclitols and densely functionalized chiral linear or cyclic molecules [74,75]. 

Remarkable selectivity has been observed in the oxidation of molecules containing several secondary hydroxyl groups, such as al-dopentopyranosides, 6-deoxyaldohexopyranosides, cyclitols, and various anhydro derivatives. As indicated previously, attack usually occurs at relatively hindered hydroxyl groups. When aqueous solutions of benzyl /3-D-arabinopyranoside, benzyl jS-D-ribopyranoside,... 

The cyclitols have provided much information on the relationship between the reactivities of secondary hydroxyl groups towards cata-... 

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