Myo-inositol derivatives

Two other myo-inositol derivatives have been selectively alkylated. Reaction of DL-l,2 4,5-di-0-cyclohexylidene-myo-inositol with benzyl chloride-potassium hydroxide in benzene, followed by removal of the acetal groups, gave DL-1-O- and DL-4-O-benzyl-myu-inositol in the ratio of 5 2, whereas, under similar conditions, DL-1,2 5,6-O-cyclohexylidene-myo-inositol gave311 the same ethers in the ratio of 57 10. These results are not readily explicable in the absence of knowledge of the conformations adopted by the cyclic acetals. 

Chelation complex (95) has been proposed to account for the regio- and diastereo-selective formation of myo-inositol derivatives (96) by cleavage of orthoesters with 1-2 equiv. of Grignard reagents in benzene-diethylether. ... 

The regioselectivities of myo-inositol derivatives towards electrophiles have been studied by using various levels of quantum mechanical calculation.66 The calculations appear to favour the 0(6) position, but experimentally the 0(3) position is the major site for electrophilic attack. Such experiments usually involve rather polar solvents and repetition of some of the calculations for molecules embedded in a medium of dielectric constant of 40 found 0(3) to be preferred as reaction site. 

Reductive coupling of dialdehydes may also be accomplished by use of samarium(II) iodide514. The reactions is stereoselective and has been used to prepare myo-inositol derivatives (equation 132)515. The equivalent reaction, using low-valent titanium species as catalysts, results in a mixture of products516. The production of cyclic /1-amino alcohols may be accomplished in good yields, and with a high degree of cis selectivity by the treatment of carbonyl hydrazones with samarium(II) iodide (equation 133)517. This reaction is effectively equivalent to an aza-Barbier reaction. 

In continuation of their studies of the resolution of myo-inositol derivatives via their orthoesters with sugar derivatives, Evstigneeva et al. [296] converted the racemic 1,2 3,4-di-O-cyclohexylidene-wyo-inositol (431) by transesterification with the mannose orthoester (425) into a mixture of diastereoisomers (426) formed by esterification of the 5- and 6-positions of (431). One of the four possible isomers was separated by crystallisation and the other three were obtained by preparative TLC. Partial hydrolysis of the resolved isomers gave both enantiomers of 1,2-0-cyclohexylidene-myo-inositol (432). 

Partial benzylation with powdered potassium hydroxide as a base and toluene as a solvent was used some 50 years ago for the preparation of 1,6-anhydro-2,4-0-benzyl-P-D-glucopyranose [79]. Since that time, other solvents, such as benzene [80-82], 1,4-dioxane-toluene mixtures [83, 84], or excess benzyl chloride [82, 85] were used as well, with apparent effects on the regioselectivity. Thus, the axially oriented secondary hydroxyl group of lL-l,2,3,4-tetra-0-benzyl-c/i ro-inositol is more reactive than the equatorial one using benzyl chloride alone (ratio of 79 21), whereas the opposite is true (35 65) in benzene as a solvent [82]. Benzylation of myo-inositol derivatives in the latter solvent was also described [80, 81, 86]. 

At this stage it is important to briefly examine the biosynthesis of carbocyclic polyols, concentrating on six membered rings. Myo-inositol derivatives, for example, are formed from D-glucose 6-phosphate 1 by a stereospecific ring-closure under the catalytic influence of inositol cyclase (Scheme 1) [lb]. 

Another example of the impact of neighbouring protected hydroxyl groups on the diastereoselectivity of pinacol couplings can be found in d Alarcao s studies on the synthesis of the myo-inositol derivative 10 (Scheme 5.10).21... 

Table VI also lists the numerous reactions that have been performed on dibutylstannylene acetals of inositol derivatives containing ds-diols, mostly in myo-inositol derivatives. Most reactions were alkylation reactions and, almost without exception, single products were obtained with the substituent on the equatorial oxygen atom. In most cases, yields were greater than 80%, and in only a few cases were yields lower than 70%.

An additional complicating issue should be kept in mind when reading the seminal pre-1968 literature, myo-Inositol derivatives that are currently designated D configuration were assigned L configuration and vice versa in the literature published before 1968. The reasons for the pre-1968 nomenclature are as follows before 1968, rules of carbohydrate nomenclature dictated that the orientation of highest numbered chiral carbon, C-6 in this case, specify the... 

In this article, the current designation will be followed the symbol Ins will be used to denote myo-inositol derivatives. The symbol I will be used to indicate inositol, the unspecified stereoisomerism. 

In the next section, we describe the osmolyte strategy plants adopt against drought, high salinity, and cold stresses, especially the role of myo-inositol derivatives including myo-inositol-1 -phosphate, D-ononitol, D-pinitol, galacti-nol, and raffinose. 

Selective alkylation and acylation of a vic-diol. Selective acylation or alkylation of cyclohexanoid, axial-equatorial oic-diols is possible by way of the dibutyl-itannylene derivative, obtained by reaction with bis(tri-n-butyltin) oxide. A typical reaction is formulated for a myo-inositol derivative in equation (1). The method... 

Optically pure inositol intermediates are very useful for synthesising D-myo-inositol 1,4,5-trisphosphate, which was found to be a second messenger. Ozaki et al [73] studied the resolution of racemic di-O-cylohexylidene-myo-inositol derivatives 17 and 18 by lipase-catalyzed esterification in organic solvents. Lipase from Candida cylindracea exclusively acetylates the hydroxyl group at C-4 or at C-5 of the D-enantiomer of 17 or 18, respectively. Around 100% e.e s of monoacetate products and unreacted starting compounds were obtained. The efficiency of the resolution is affected by the solvent, the most hydrophobic solvents ethyl ether and benzene being more effective than the water miscible solvents such as acetone, THF, and dioxane. 

Weak bases can also induce ring opening with the aid of an oxaphilic reagent. Thus, the oxygen bridge in oxabicyclo[2.2.1]heptanone 177 was cleaved in the presence of triethylamine and TMSOTf to generate enone 178, which was an intermediate in the first total synthesis of (-)-conduritol C, Eq. 114 [93]. TBDMSOTf/triethylamine is also an effective combination for this transformation and has been used in the synthesis of myo-inositol derivatives, as well as (-)-conduritol B from 179, Eq. 115 [167,168]. (+)-Conduritol F has also been prepared by this route which served to confirm its structure and demonstrate it was identical to natural (+)-leucanthemitol [168], Fig. 5. 

Table 11.1-21 lists cyclic secondary alcohols that have been synthesized by lipase-catalyzed enantiomer-differentiating acylation (1-129). The compounds that have been obtained by the alternative route of hydrolysis are listed in Table 11.1-16. The complementary nature of the two routes is obvious. For the series of the glycals 9-15, Pseudomonas cepacia lipase-catalyzed acylation works with good to high enantiomer selectivity and yield. myo-Inositol derivatives 17 and 18 may be prepared enantiomer-...

Cyclohexylidene and isopropylidene monoketals 47 and diketals 48, 49, and 50 are well-known protected myo-inositol derivatives (Scheme 3-1). Compounds 47 ketalized at the 1,2-cis-positions have been utilized conveniently for the synthesis of various inositol phosphates since 47 can be regioselectively functionalized and prepared in good yield by the conventional ketalization procedure and subsequent partial deprotection of the less stable trans-type ketals from the diketal mixture formed first in the reaction.22 Three diketals S have been also often employed for the synthesis of target inositol derivatives, because they have the following advantages (1) A trans vicinal hydroxyl moiety as well as the 1,2-... 

Contrary to the results described above (Scheme 4-19), highly diastereoselective osmylation of cyclohexene derivatives 258 with the more bulky substituent, TBDMS, on one side of the double bond, which were derived from oxanorbornenone 257, was reported. This afforded the suitably protected chiral myo-inositol derivatives 259 (Scheme 4-20 ). 9 ... 

Nucleophilic substitution with inversion or retention of configuration of an inositol ring carbon is used to obtain inositol derivatives stereoselectively with the desired configuration. The reaction has been often employed when myo-inositol derivatives are derived from other starting materials such as natural products and arenes. 

Reports on the preparation of 2-a-mannopyranosyl-1-phosphatidyl-D-myo-inositol were published in 1977 (Ref.117) and 1989.118 After these reports, recently the 2,6-dimannoside (PIM2, 363) has been synthesized. Van Boom s groupie introduced the mannosyl moieties to the 2 position and subsequently to the 6 position in myo- inositol derivative 359 to yield 361. Dimannoside 361 was phosphorylated after removal of the allyl group by the H-phosphonate method and finally deprotected giving the final product PIM2 (Scheme 6-6). ... 

A long series of papers by Shvets and co-workers is devoted to synthesis of asymmetrically substituted myo-inositols and, in particular, inositolphos-phatides. Their route to optically active compounds from wyo-inositol consists of the formation of diastereoisomeric orthoesters in the reaction of a suitably protected racemic myo-inositol derivative with the orthoacetate of D-mannose, followed by the separation of the diastereoisomers and hydrolysis. Naturally occurring ( + ) and (-) bomesitols (3- and 1-0-methyl-sn-myo-inositols) were obtained in this way, among many other enantiomerically pure chiral myo-inositol derivatives. ... 

Syntheses of ( ) myo-inositol 1,2-bisphosphate and myo-inositol 1,2,3-trispho-sphate by phosphorylation of ( ) 3,4,5,6-tetra-O-benzyl-myo-inositol and 4,5,6-tri-O-benzoyl-myo-inositol, respectively, using dibenzyl AT.iV -diisopropylpho-sphoramidite then oxidation have been reported, and d- and L-myo-inositol 1,4,6-trisphosphate has been made from a myo-inositol derivative and resolved with (5)-(+)-0-acetylmandelic acid to obtain the required pure enantiomers. Full details of an earlier report (see Vol. 27, p. 222, ref. 146) on the syntheses of L-Jcy//o-inositol 1,2,4-trisphosphate, scyllo-inositol 1,2,4,5-tetrakis-phosphate and -phosphorothioate and 2-deoxy-2-fluoro-D,L-myo-inositol have been reported. ... 

Three myo-inositol derivatives, ( )-3,6-di-0-valproyl-l,2 4,5-di-0-iso-propylidene-myo-, (+ )-3,6-di-0-valproyl-4,5-0-isopropylidene-myo- and (+)-3,6-di-O-valproyl-myo-inositol have been prepared as valproic acid (2-propyl-pentanoic acid) prodrugs for anticonvulsant studies. The last compound, resulting from acid hydrolysis of either of the first, was found to exhibit an anticonvulsant activity four times higher than that reported for valproic acid. ... 

The glycosylation of the OH-6 group of the myo-inositol derivative 141 with 2-azido-2-deoxy-D-glucopyranosyl trichloroacetimidates is another case of regioselective glycosylation of a 1,2-trans-O-diequatorial diol system 141 which is frequently performed for the preparation of building blocks for IPG synthesis [53]. 

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