Cyclitols

For more information see Fludlicky, T., and Cebulak, M., Cyclitols and Their Derivatives (New York VCH, 1993). 

The most important cyclitols are the inositols (1,2,3,4,5,6-cyclohexanehexols). The relative arrangement of the six hydroxyl groups below or above the plane of the cyclohexane ring is denoted by an italicised configurational prefix in the eight inositol stereoparents (the numerical locants indicate OH groups that are on the same side of the ring)  

Six of these isomers (scyllo-, myo-, epi-, neo-, cis-, and muco-) have one or more planes of symmetry and are mei o-compounds cfiiro-inositol lacks a plane of symmetry and exists as the d- and 

L-forms. In myo-inositol, the plane of symmetry is C-2/C-5 unsymmetrically substituted derivatives on C-1, C-3, C-4, and C-6 are chiral. Substitution at C-2 and/or C-5 gives a meio-product. fl/to-Inositol appears to have a plane of symmetry, but at room temperature it is actually a racemate formed of two enantiomeric conformers in rapid equilibrium. 

The simple carbohydrates include a substantial number of carbocyclic substances known as cycU-tols. Of special biochemical interest are the variety of cyclitols known as inositols. These are based on a ring of six carbon atoms with OH groups attached to each. Inositol has nine isomeric forms, all of which have been prepared (Table 10.6). 

The most widely distributed isomer is myo-inositol, which is present in nearly all living species, both in free and combined form. 

In animals, the myo-inositol is combined with phospholipids, while in plants it occurs mainly as salts of myo-inositol hexaphosphate, which is also known as phytic add (10.36a). 

In soil, phytic acid forms insoluble complexes with Ca, Fe and Al, and since these complexes are reasonably stable, they tend to accumulate. In some localities the phytic acid content can reach as much as 50% of the total organic phosphorus which is present. 

Phytic acid occurs as a calcium or magnesium salt in dried peas, beans, husks and cereal grains. Phytates accumulate in seeds and up to 90% of the seed phosphate can be in this form. About 75% of the phosphorus in soy beans is present as phytate. 

Dambonitol (1,3-di-O-methyl-myo-inositol) has been identified as a constituent of glycosyl nervogenic acid esters from Anodendron 

Improved procedures have been described for the synthesis of ( )-1,2 4,5-di-O-isopropylidene-myo-inositol (34), which was 

Penta-O-benzyl-sn-myo-inositol (40) has been resolved by formation of a diastereoisomeric mixture of o -D-mannopyranoside derivatives (ortho-ester route), which could be separated and hydrolysed 

Calculations show that the conformational energies for myo-inositol 4,5-diphosphate increased from 840 to 1369 kJmol. as the charge on phosphorus increases from zero to 

Nadirov, A.M.Ashirov, B.Sh.Kedel baev, and V.F.Pechenkina, Gldrollz. Lesokhim. Prom-st., 1985, 8 (Chem.Abstr., 1985, 102, 133 792). 

Although not strictly sugars, polyhydroxylated carbocylic rings have many of the non-anomeric reactions of carbohydrates proper, and because of the 

The basic lUPAC system of nomenclature is straightforward the compounds are named as cycloalkane polyols, with a slash separating substituents on each side of the ring thus, 1,2,3/4,5 cyclopentane pentol has three adjacent hydroxyls on one side of the ring, and two on the other (there are four cyclopentane pentols, all achiral). 

Trivial names are also given to tetrahydroxylated cyclohexenes, conduritol. These are given letters in the sequence of their discovery. Only conduritols A and F occur naturally. 

The commonest naturally-occurring inositol is myu-inositol, and its structure is readily memorised because in the preferred conformation only one hydroxyl group is axial. Its 1-L phosphate ester is biosynthesised from its isomer glucose-1-phosphate by an oxidation-intramolecular aldol condensation-reduction sequence, see Section 6.8.4. 

For a recent protocol, and a discussion of the reaction see N. Adje, F. Vogeleisen, and D. Uguen, Tetrahedron Lett., 1996, 37, 5893. 

The Perrier synthesis of deoxyinoses from 6-deoxy-hex-5-enopyranose 

Many papers reflect increasing interest in the synthesis of pseudo-sugars. A synthesis of acetyl ate pseudo-p-L-mannopyranose (32) starts from D-ribose and uses an inter- and an intra-molecular 

Knoevenagel reaction to lengthen the chain and then form the ring 41 

Derivatives of pseudo-D-glucosamine and pseudo-L-idosamlne have been synthesized from the cyclohexanone (35) by conventional proced- 

Further examples of the 1,6-anhydro-pyranose— cyclitol rearrangement (see Vol. 18, p. 170) have been published, e.g., 

Reagents i, AcOH-HgO ii, NalO iii, MeNOj-MeONa iv, Hj-Ni v, AcjO-py 

Tadano, and S. Horiuchi, Bull. Chem. Soc. Japan, 1975, 48, 2895. 

The rates of displacement of the sulphonate group by azide ion in DMF at 110 °C have been measured for a series of toluene-p-sulphonyl and p-bromo-benzenesulphonyl derivatives of 3-0-methyl-cA/ra-inositol and 4-0-methyl-tf// -inositol in these compounds, the arylsulphonate group was located at position 4 (or 3), and the substituents at positions 1,2, 5, and 6 were isopropylidene, acetyl, methyl, and cyclic carbonate. All of the resulting azides (except the unreactive penta-O-methyl-c/j/ra derivative) could be converted into one of two inosamine penta-acetates, viz. lL-2-amino-2-deoxy-l-0-methyl-a//o-inositol and 1d-3-amino-3-deoxy-4-0-methyl-c/ /ra-inositol penta-acetates. The results were discussed in terms of currently held views on displacement reactions with carbohydrate and related sulphonates. 

Prinzbach, R. Keller, and R. Schwesinger, Angew. Ghent. Internat. Edn., 1975, 14, 632. Bosa Prinzbach, R. Keller, and R. Schwesinger, Angew. Ghent. Internat. Edn., 1975,14, 633. 

D-Pinitol (from Mimosa pudicd) and pinpollitol (from Firms radiata) have been identified as 4-O-methyl- and l,4-di-0-methyl-D-c o-inositol [(337) and (338) respectively. 

A highly phosphorylated, monomeric form of n-inositol ( pre-mannose ) has been detected on the cell surface of a strain of Amoeba discoides.  

1-Amino-l-deoxy-j-cy/Zo-inositol (339) has been prepared by hydrogenolytic reduction of the corresponding 3,4-di-O-benzyl-l-deoxy-l-nitro-derivative, which was obtained by base-catalysed cyclization of 2,3-di-0-benzyl-6-deoxy-6-nitro-D-glucose.  

Racemic (l,3/2)-l-benzyloxycarbonylamino-3-0-ethyl- and (l,2/3)-3-benzyl-oxycarbonylamino-l-O-ethyl-cyclohexanediols (prepared from 3-ethoxycyclo-hexene) have been condensed under Koenigs-Knorr conditions with 3,4,6-tri-O-acetyl-2-deoxy-2-(2,4-dinitrophenyl)amino-a-D-glucopyranosyl bromide to yield 

44 for related work). Similar cycloadditions of dienyl pyrrolidinones [le. AT-(peiita-l,3-dienyl)- or -(buta-l,3-dienyl)-pyrolidin-2-one] with the in situ generated acyl nitroso compound derived from benzyl-JV-hydroxy-carbamate with periodate have led to the preparations of racemic pyroUidines 56 and 57 (R = H or Me). The latter compound is thought to exist as a dimer. An asymmetric synthesis of l,S,6-trideoxy-l,5-imino-D-altritol in which the piperidine ring is formed from a pyiidinium ring bearing Seebach s oxazolidinone chiral auxiliary has also been described.  

5-Dihydrocyclopentene derivatives (from cyclopentadiene) after kinetic resolution with a lipase are useful precursors for the synthesis of 1-deoxy-D-nojirimycin, and benzene cis-diol (from benzene by microbial oxidation) has been used as a precursor to 1-deoxy-D-galactonojirimycin and bicyclic derivative 59. The preparation of imino-alditol derivatives in which the imino nitrogen atom is part of a fused tetrazole ring is mentioned in Chapter 10 and the synthesis of imino-lactams is covered in Chapters 10 and 16. 

---

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-... 

---