Synthesis cyclitol

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

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. 

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... 

New Approaches to the Synthesis of Nitrogenous and Deoxy Sugars and Cyclitols... 

One of the efficient method for constructing carbohydrates is the Diels-Alder reaction, which gives a variety of important synthetic intermediates for the synthesis of cyclitol derivatives. We therefore were interested in the development of asymmetric Diels-Alder reaction by the use of chiral titanium reagents. 

The known adduct (385) of furan and vinylene carbonate, previously used for the synthesis of some cyclitols,256,257 has been transformed into DL-ribose derivatives. After hydroxylation of 385 and subsequent formation of the isopropylidene derivative, the carbonate group was removed by treatment with barium hydroxide, and the resulting diol was cleaved by oxidation with permanganate. Dicarboxyl-ic acid 386 gave, upon treatment with acetic anhydride, cyclic anhydride 387. The reaction of 387 with azidotrimethylsilane produced... 

M. Funabashi and J. Yoshimura, Branched chain sugars. Part 14. Synthesis of new branched-chain cyclitols having myo- or scyllo-, and muco-configuration from 3-< -benzyl-5,6-dideoxy-5-C-(l,3-dithian 2-yl)-6-nitro-L-idofuranose and D-glucofuranose, J. Chem. Soc. Perkin Trans, p. 1425 (1979). 

M. C. McIntosh and S. M. Weinreb, A strategy for synthesis of conduritols and related cyclitols via stereodivergent vinylsilane-aldehyde cyclizations, J. Org. Chem. 56 5010 (1991). 

In a related contribution O Brien described the AA on styrenes and converted the amino alcohols into enantiopure diamines by using a reaction strategy similar to Janda s [83], Further synthetic applications of the AA include a new access to Evans chiral oxazolidinones [84], the enantioselective synthesis of a-amino ketones from silyl enol ethers [85], the stereoselective synthesis of cyclohexyl norstatine [86], and a route towards amino cyclitols by aminohydroxy-lation of dienylsilanes [87]. 

The regioselectivity of the migration in Baeyer-Villiger oxidation of ketones is very dependent upon substituents attached to carbon atoms adjacent to the ketone. In a study128 of the MCPBA oxidation of polyhydroxycyclohexanone derivatives, the regioselectivity of the reaction has been carefully identified. This should prove useful to synthetic chemists when planning to use this type of reaction, since cyclitols are important synthons in natural product synthesis. 

Fabris F, Collins J et al (2009) Investigation of steric and functionality limits in the enzymatic dihydroxylation of benzoate esters. Versatile intermediates for the synthesis of pseudo-sugars, amino cyclitols, and bicyclic ring systems. Org Biomol Chem 7 2619-2627... 

Raney Ni has also been used for removal of a secondary bromine, and has been applied for the synthesis of deoxy cyclitols with addition of Amberlite IR-4B anion-exchange resin to bind the liberated acid202 205 (eq. 13.110204). 

Thiosugars can be rapidly synthesized when sulfur-substituted aldehydes are condensed with DHAP under the influence of FDP aldolase.42 The synthesis of these heterocycles is completed by phosphate cleavage, acetylation and reduction of the resultant ketone (Scheme 5.20). Cyclitols, another interesting class of biologically active compounds, have been prepared through the reaction of phosphonate- and nitro-substituted aldehydes with DHAP under the influence of FDP aldolase (Scheme 5.21) 43,436... 

Scheme 5.21. Chemoenzymatic synthesis of cyclitols. P = PO32, Pase = phosphatase.

R. Ahluwalia, S. J. Angyal, and B. M. Luttrell, Cyclitols. XXXI. Synthesis of amino- and nitro-cyclopentanetetrols, Aust. J. Chem., 23 (1970) 1819-1829. 

Cyclitols. A novel synthesis of conduritol (6) from benzoquinone utilizes 1 for protection of one C=C bond and for differentiation of the carbonyl groups. Reaction of the quinone with 1 gives the Diels-Alder adduct 2, which is converted selectively into 4,... 

An interesting application of sequential oxyselenenylation reactions was reported recently by Kim for the synthesis of biologically important cyclitols [41,42]. Both, the stereochemistry and the regiochemistry of the sequential oxyselenenylation of cyclohexene, were controlled by the use of chiral diol hydrobenzoin as the nucleophile. Illustrated in Scheme 5 are the various steps employ-... 

Scheme 5. Serial Oxyselenenylation Reactions. Synthesis of Cyclitols...

Apparently complete replacement of the hydroxyl groups in meso-inositol by halogen has never been accomplished. The reverse procedure, hydrolysis of the benzene hexahalides, has likewise failed although Milhorat and Barthels have claimed the synthesis of an a-tocopheryl ether of a cyclitol by heating a-tocopherol with benzene hexachloride in absolute alcoholic potassium hydroxide under an atmosphere of nitrogen. 

---