Of conduritols

Conduritols and inositols are cyclic polyalcohols with significant biological activity. The presence of four stereogenic centers in the stmcture of conduritols allows the existence of 10 stereoisomers. Enzymatic methods have been reported for the resolution of racemic mixtures or the desymmetrization of meso-conduritols. For example, Mucor miehei lipase (MML) showed enantiomeric discrimination between all-(R) and all-(S) stereoisomers ofconduritol E tetraacetate (Figure 6.52). Alcoholysis resulted in the removal of the four acetyl groups ofthe all-(R) enantiomer whereas the all-(S) enantiomer was recovered [141]. 

The wide scope of the application of conduritol epoxides for the active-site-directed inhibition is seen from the data given in Table XI. Only a few... 

Analogs of conduritols from toluene cA-dihydrodiol by reaction with singlet oxygen followed by scission with thiourea (Figure 8.7d) (Carless et al. 1989). 

Reduction of 166 with NaBH4/CeCl3 in aqueous MeOH afforded the protected, chiral derivative 169 of Conduritol-D in 73 % yield. Conduritol-D (170) was formed nearly quantitatively upon acid hydrolysis of 169. Treatment with Ac20/pyridine gave the crystalline tetracetate 171. Reduction of 165 with diisobutylaluminium hydride (DIBAL) in toluene (-80 °C, 6 h) gave 172, another chiral derivative of Conduritol-D, in 97 % yield. Alternatively, 167 was reduced with LiAlH4 (THF, -90 °C, 6 h) into 173 (95 %). Deprotection of 167 with tetrabutylammonium fluoride... 

The stoichiometric approach has been successfully used as the key step for the synthesis of biologically active compounds, to obtain enantioenriched allylic alcohols, as illustrated by the synthesis of conduritols derivatives 84 or the aggregation pheromone of the Douglas-fir beetle 85 , as well as enantioenriched oxiranes, intermediates for the synthesis of (—)-isomenthone 86 ° (Scheme 34). 

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). 

The kinetic resolution of C2-symmetric racemic substrate as shown in Scheme 8E.22 requires differentiation between the starting material and the monoalkylated product 113 in addition to the enantiodiscrimination in the ionization step. With a bulky carboxylic acid as nucleophile, the racemic tetraacetate of conduritol B was efficiently resolved under phase-transfer conditions [68]. Further elaboration of the hydrolytically desymmetrized alcohol resulted in the synthesis of the important glycosidase inhibitor, (+)-cyclophellitol. 

Scheme 8E.22. Kinetic resolution of conduritol B and synthesis of cyclophellitol.

Finn KJ, Collins J, Hudlicky T (2006) Toluene Dioxygenase-Mediated Oxidation of Dibromobenzenes. Absolute Stereochemistry of New Metabolites and Synthesis of (-)-Conduritol E. Tetrahedron 62 7471... 

Ley SV, Redgrave AJ (1990) Microbial oxidation in synthesis concise preparation of (+)-conduritol F from benzene. Synlett 1990 393-394... 

Mehta G, Lakshminath S (2000) A norbornyl route to cyclohexitols stereoselective synthesis of conduritol-E, alio-inositol, MK 7607 and gabosines. Tetrahedron Lett 41 3509... 

Diacetoxy-1,3-butadiene is a reactive diene in the Diels-Alder reaction. It has been used as the starting material in stereospecific syntheses of conduritol-D8 and shikimic acid,9,10 and in a simple general method of preparation of benzene derivatives, especially unsymmetrical biphenyls.11,12... 

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,... 

Metha, G. et al. A Norbornyl Route to Cyclohexitols Stereoselective Synthesis of Conduritol-E, aWo-Inositol, MK 7607 and Gabosines. 3.3 2000 [154]... 

Kna 7 has used the oxyanion-accelerated rDA reaction to advantage in the synthesis of conduritol A. The masked dienol used was 9-[(benzyloxy)methoxy]anthracene (81), which upon reaction with benzo-quinone (82) gave the protected adduct (83) (equation 38). Further transformations yielded (84), which upon treatment with potassium hydride caused rDA fragmentation to occur at 35 °C. Two subsequent steps produced conduritol A (86a), a naturally occurring cyclitol, in 39% overall yield from (82). The room-temperature DA activity of anthranol reported by Rickbom, coupled with the observed low-temperature rDA reactivity of its adducts, makes anthranol a highly useful alkene protecting group via a DA/iDA sequence. 

D-Xylose derivative 7 has a latent plane of symmetry, the terminal hydroxyl and carbonyl groups being virtually enantiotopic. With adapted reactions and a judicious order of performing them (Scheme 4), the two enantiomeric intermediates 8 and ent-S were prepared [45], They are interesting starting materials for further diastereodivergent synthesis of conduritol and inositol derivatives [46],... 

D-Xylose has been used as starting material in the synthesis of (+)-Conduritol C [88] and cyclophellitol [56] (Scheme 12). The combinatitMi of the zinc-mediated tandem reaction with RCM was also used in the synthesis of 7-deoxypancratistatin, a naturally occurring compound with activities against different cancer types. In the latter synthesis, the longest reaction sequence involves 13 steps from o-xylose with a 4% overall yield [58] (Scheme 12). 

Scheme 12 Syntheses of (+)-conduritol C, cyclophellitol and 7-deoxypancratistatin using the two-step strategy reductive ring opening of 5-iodo-D-xylofuranoside and ring-closing metathesis...

Scheme 13 Syntheses of benzylated derivatives of conduritol B, conduritol F, myo-inositol and cArro-inositol...

Unsurprisingly, the nitrogen analogue of conduritol epoxide inactivated GH 13 yeast ot-glucosidase and a GH 1 p-glucosidase from Agrobacterium faecalis the inactivation appeared faster than with conduritol B epoxide itself. 

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. 

On catalytic oxidation, conduritol C (66) gives (in just 10 min.) the ketone (66a), the quasi-equatorial hydroxyl group at C-1 (but neither the axial hydroxyl group at C-2 nor the quasi-equatorial hydroxyl group at C-4) being oxidized. The same ketone (66a) can also be prepared by oxidation of natural conduritol A (67). Both possible half-chair conformations of conduritol A (67) are equally stable, and hence there presumably exists an equilibrium in which the group at C-1, as well as that at C-4, is attacked and a racemate (66a) is produced. 

Dangschat and Fischer, in an elegant elucidation of the structure of conduritol (16), a naturally occurring cyclitol, isolated the tetraacetate... 

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