1235. Cyclitols. Part XX. Cyclohexylidene ketals of inositols

Angyal, S. J.; Irving, G. C. J.; Rutherford, David T.; Tate, M. E.

doi:10.1039/jr9650006662

Cited by 38 publications

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“…The organic phase was then separated, and the aqueous phase was washed with toluene. Finally, the combined organic phases were washed with saturated NaCl solution, dried over Na 2 SO 4 [16,17] 8.50 g, 24.0 mmol) in pyridine (15 mL) and CH 2 Cl 2 (15 mL). Stirring was continued at room temp.…”

Section: Methodsmentioning

confidence: 99%

“…[α] Dpentol (12): Iodine (9.1 g, 35.8 mmol), triphenylphosphane (10 g, 38.1 mmol) and imidazole (4.0 g, 58.7 mmol) were added (under argon) to a solution of -3,4:5,6-di-O-cyclohexylidene-2-O-methylchiro-inositol [16,17] (7.28 g, 20.6 mmol) in dry toluene (400 mL). After it had been heated at reflux for 3 h, the mixture was cooled down.…”

Section: Methodsmentioning

confidence: 99%

“…The cyclitols 6 and 7 were similarly synthesized from -quebrachitol (9) via the common key intermediate 3, (10). [16,17] Substitution of its free OH group by iodine or benzoylation resulted in the compounds 11 and 14, respectively (Scheme 3). The iodination procedure was carried out analogously to that reported in ref.…”

Section: Synthesis Of the Starting Materialsmentioning

confidence: 99%

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Competition between Non‐Classical Single and Double Epimerizations in Cyclitol Chemistry

et al. 2004

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Two competitive regio‐ and stereoselective epimerization reactions were investigated in four cyclitols characterized by four contiguous OH groups with a cis‐trans‐trans sequence and by varied substituents (OMe, OBz, F, H) adjacent to this tetrol unit. The starting materials were synthesized from L‐quebrachitol (compounds 5−7) and myo‐inositol (compound 8). Their acetalization with the chloral/DCC reagent system gave cyclic acetals with one epimerized chiral ring atom and also with two epimerized chiral centres. The single epimerization takes place exclusively at the middle C‐atom of the cis‐trans triol unit in the tetrol sequence (products 15, 17, 19/20 and 24−27), whereas the double epimerization occurs at both of the "centrally located" C‐atoms in the cis‐trans‐trans tetrol unit (products 16, 18, 21 and 28). The product ratios of singly to doubly inverted compounds change as follows: the lower the electron‐withdrawing effect of the substituents adjacent to the tetrol unit, the higher the percentage of the corresponding doubly inverted product. However, the singly inverted products remain the major products in all cases. X‐ray analyses are given for the starting material 1‐fluoro‐2‐O‐(methyl)cyclohexane‐2,3,4,5,6‐pentol (5) and for the products 1‐O‐cyclohexylcarbamoyl‐2,3‐O‐(2,2,2‐trichloroethylidene)5‐O‐(methyl)cyclohexane‐1,2,3,4,5‐pentol (17), 3‐O‐acetyl‐1‐O‐benzoyl‐6‐O‐cyclohexylcarbamoyl‐2‐O‐methyl‐4,5‐O‐(2,2,2‐trichloroethylidene)‐muco‐inositol (22) and 2,3‐di‐O‐ethylidene)‐(+/‐)‐chiro‐inositol (24). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Synthesis Of the Starting Materialsmentioning

confidence: 99%

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Competition between Non‐Classical Single and Double Epimerizations in Cyclitol Chemistry

et al. 2004

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“…An LKB 2138 Uvicord S, equipped with a microflow cell and a 254-nm filter, was used to monitor the effluent. For preparative HPLC, a stainless steel column (5.1 x 50 cm) (HT Chemicals, Saint Louis) was packed manually with Merck LiChroprep RP-18 (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) ,um) (EM Scientific, Cherry Hill, NJ) and eluted with methanol/water at a flow rate of 20 or 25 ml/min. The UV detector was equipped with a preparative flow cell, and solvents were mixed and delivered by a Waters Prep LC3000 system fitted with a 15-ml injection loop.…”

Section: Methodsmentioning

confidence: 99%

Chiral synthesis of D- and L-myo-inositol 1,4,5-trisphosphate.

Tegge

Ballou

1989

Proc. Natl. Acad. Sci. U.S.A.

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Chiral inositols (D-chiro-inositol from Dpinitol and L-chiro-inositol from L-quebrachitol) were converted to the 3,4-di-O-benzyl ethers, which were selectively benzoylated to yield the 1,2,5-tri-O-benzoyl-3,4-di-O-benzylchiro-inositols. The free hydroxyl group in each derivative was inverted by way of the trifluoromethane sulfonate ester to provide D-and L-1,2,4-tri-O-benzoyl-5,6-di-O-benzyl-myoinositol. Hydrogenolysis to remove the benzyl ether groups gave the enantiomeric 1,2,4-tri-O-benzoyl-myo-inositols, which were phosphorylated by a dibenzylphosphite triester method. After hydrogenolysis and saponification of the derivatives, the D-and L-myo-inositol 1,4,5-trisphosphates were isolated as the crystalline cyclohexylammonium salts in gram quantity.myo-Inositol-containing phospholipids were isolated from bovine brain by Folch in 1942 (1) and from soybeans by Woolley in 1943 (2), and a more highly phosphorylated form was obtained from brain tissue in 1949 (3). Folch called the latter preparation "diphosphoinositide" because it yielded an "inositol metadiphosphate" following strong acid hydrolysis, but the known susceptibility of inositol phosphates to acid-catalyzed migration suggests that the product must have been a mixture. The general nature of the inositol phosphates from brain lipids was reported by Grado and Ballou (4) and Dittmer and Dawson (5) in 1960, who concluded that it was composed of myo-inositol mono-, di-, and triphosphates. Characterization of the myo-inositol monophosphate from soybean inositol phospholipid (6), synthesis of its enantiomer (7), and characterization of the myo-inositol polyphosphates from brain inositol phospholipid (8, 9) followed, and the exact nature of the phospholipid complex was reported by Brockerhoff and Ballou in 1961 (10). These results were confirmed by Brown and Stewart (11).Although the brain inositol phospholipid complex was shown to have an active metabolism in tissue slices with respect to the turnover of the monoesterified phosphate groups (12-15), studies reported by Hokin and Hokin (16) failed to establish a specific physiological role for the inositides. Regardless, these workers are recognized for promoting the hypothesis that the inositol phospholipids were involved in specific cellular processes. Developments of the last decade that have elucidated the role of myo-inositol polyphosphates as second messengers have given new focus to this field of lipid metabolism (17), and the renewed interest has stimulated the development of synthetic procedures for the preparation of such derivatives. In studies published to date (18-23), the syntheses have started with myo-inositol, a meso compound, and have yielded racemic products that must be resolved to provide the natural isomer. In this report, we describe chiral syntheses of myo-inositol 1,4,5-trisphosphate that yield the optical antipodes directly and that follow a synthetic strategy that should facilitate the preparation of other useful derivatives. (27)] was prepared by the procedure of Jiang and Ba...

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“…Angyal and co-workers, who pioneered the use of the cyclohexylidene protecting groups with inositols, noted that 'in larger concentration, pTsOH promotes the self-condensation of cyclohexanone, producing water which actually represses formation of the desired ketal'. 131 The reaction was also attempted in neat refluxing cyclohexanone with catalytic pTsOH, however in this case 274 was isolated from the reaction in only 37% yield. Thus, a new, improved procedure, eliminating the toxic benzene and chloroform was designed that involved treatment of quebrachitol with 1,1-dimethoxycyclohexane (275) under acidic conditions (scheme 5.2 overleaf).…”

Section: Chapters Six and Seven Of This Thesismentioning

confidence: 99%

Towards a Total Synthesis of Peloruside A and the Preparation of Selected Inositol Derivatives

Baars¹

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<p>This thesis covers two broad areas of work under the general theme of the synthesis of bioactive and/or synthetically useful compounds based on natural products or deriving from the chiral pool. Chapters one, two and three focus on the marine secondary metabolite peloruside A (1), which has been shown to stabilise microtubules during mitosis and hence cause apoptosis (cell death) in a similar manner to the very successful anticancer drug Taxol. A synthetic program with the aim of devising a total synthesis was initiated at Victoria University of Wellington after peloruside A's discovery in 1999. Four synthetic disconnects were identified in the retrosynthetic analysis of peloruside A: to give the C-l to C-2 fragment; the C-3 to C-7 fragment; the C-8 to C-11 fragments; and the C-12 to C-24 fragment. The C-7 to C-8 bond was to be formed via an asymmetric aldol reaction to give the pyranose ring fragment (highlighted in blue). In this thesis, the synthesis of the C-3 to C-7 fragment is described. A1do1 reactions with the C-8 to C- 11 ketone have been investigated, and subsequent progress towards the assembly of the pyranose ring fragment is presented. Chapters four, five, six and seven describe the preparation of selected synthetically and biologically useful derivatives of the commercially available inositols, quebrachitol (L-chiro-inositol-2-methyl ether) and myo-inositol. The butane di-acetal (BDA) derivatives 293, 300, and 301 (as well as acetylated and methylated derivatives thereof) were prepared during work directed towards the synthesis of the inositol core of a phosphatidylinositol manno-oligosaccharide (PIM-6) isolated from Mycobacterium bovis and M. smegmatis. Quebrachitol derivatives 305, 306 and 307 were prepared and subsequently tested against myoinositol (the optimal competitor) in biological uptake assays of the microorganisms, Candida albicans and Leishmania donovani. For both microorganisms, the mono- and di-O-methylated L-chiro-inositol derivatives 307 and 305, as well as quebrachitol, gave significant inhibition results, with P values from P < 0.001 to P < 0.05 for paired-sample t-test analyses, i.e.99.9% to 95% confidence for significant inhibition, respectively. The benzoylated derivative 306 did not induce any inhibition of myo-inositol uptake. Myo-inositol is the most abundant of the inositols in nature and is readily available. However, as it is a meso compound, one of the key challenges in the use of myoinositol as a synthetic precursor is an efficient resolution method. The formation of myo-inositol camphanylidene acetal 269a is one successful solution, and work done in an attempt to better understand the selectivity of the reaction is reported here. Also, process development work was done to adapt the preparation so that it was suitable for scale-up, and a subsequent large scale synthesis of the acetal was undertaken. Previously unpublished X-ray crystal structures were obtained for 269a and, for two of the diastereomeric impurities of the reaction.</p>

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1235. Cyclitols. Part XX. Cyclohexylidene ketals of inositols

Cited by 38 publications

References 0 publications

Competition between Non‐Classical Single and Double Epimerizations in Cyclitol Chemistry

Competition between Non‐Classical Single and Double Epimerizations in Cyclitol Chemistry

Chiral synthesis of D- and L-myo-inositol 1,4,5-trisphosphate.

Towards a Total Synthesis of Peloruside A and the Preparation of Selected Inositol Derivatives

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