Tetraol derivative

Ichikawa et al. synthesized bis-benzoyl-protected 2-deoxy thietanose 87 directly from tetraol derivative 86 in 30% yield (Equation 27) C1999NAS5, 1999TL7385>. 

A synthesis of (25, 35, 45 )-3-hydroxy-4-methylproline (11) from the tetraol derivatives... 

Racemic validatol (7) and deoxyvalidatol (8) have been synthesized by the procedure outlined in Scheme 3 Racemic cyclitols have also been prepared from cyclohexene by repeated sequential allylic bromination and treatment with sodium benzyloxide to give a mixture of di(benzyloxy)cyclohexenes the 3,4-diether (9) then being hydroxylated by standard procedures leading to the tetraol derivatives (10) (the 1,2,4/3-, 1,3/2,4-, and 1,4/2,3-isomers), from which racemic dihydroconduritols could be obtained. ... 

Yamamoto et al. have reported a chiral helical titanium catalyst, 10, prepared from a binaphthol-derived chiral tetraol and titanium tetraisopropoxide with azeotropic removal of 2-propanol [16] (Scheme 1.22, 1.23, Table 1.9). This is one of the few catalysts which promote the Diels-Alder reaction of a-unsubstituted aldehydes such as acrolein with high enantioselectivity. Acrolein reacts not only with cyclo-pentadiene but also 1,3-cyclohexadiene and l-methoxy-l,3-cyclohexadiene to afford cycloadducts in 96, 81, and 98% ee, respectively. Another noteworthy feature of the titanium catalyst 10 is that the enantioselectivity is not greatly influenced by reaction temperature (96% ee at... 

We now tum our attention to the C21-C28 fragment 158. Our retrosynthetic analysis of 158 (see Scheme 42) identifies an expedient synthetic pathway that features the union of two chiral pool derived building blocks (161+162) through an Evans asymmetric aldol reaction. Aldehyde 162, the projected electrophile for the aldol reaction, can be crafted in enantiomerically pure form from commercially available 1,3,4,6-di-O-benzylidene-D-mannitol (183) (see Scheme 45). As anticipated, the two free hydroxyls in the latter substance are methylated smoothly upon exposure to several equivalents each of sodium hydride and methyl iodide. Tetraol 184 can then be revealed after hydrogenolysis of both benzylidene acetals. With four free hydroxyl groups, compound 184 could conceivably present differentiation problems nevertheless, it is possible to selectively protect the two primary hydroxyl groups in 184 in... 

Deslongchamps and coworkers [26] used a combination of a transannular Diels-Alder cycloaddition and an intramolecular aldol reaction in the synthesis of the unnatural enantiomer of a derivative of the (+)-aphidicolin (4-74), which is a diterpe-noic tetraol isolated from the fungus Cephalosporium aphidicolia. This compound is an inhibitor of DNA polymerase, and is also known to act against the herpes simplex type I virus. In addition, it slows down eukaryotic cell proliferation, which makes it an interesting target as an anticancer agent... 

Fig. 3. (Top left) Chemical methods used to depolymerize the polyesters. (Top right) Thin-layer and gas-liquid chromatograms (as trimethylsilyl derivatives) of the monomer mixture obtained from the cutin of peach fruits by LiAlD4 treatment. In the thin-layer chromatogram the five major spots are, from the bottom, C18 tetraol, C16 triol, and C18 triol (unresolved), diols, and primary alcohol. Nx = C16 alcohol N2= C18 alcohol Mj = C16 diol M2 = C18 diol D = C16 triol D2 and D3 = unsaturated and saturated C18 triol, respectively, T4 and T2, unsaturated and saturated C18 tetraol, respectively. (Bottom) Mass spectrum of component D3 in the gas chromatogram. BSA = bis-N,O-trimethylsilyl acetamide...

The tetraols were found to be highly sensitive toward acidic and basic conditions. Under Bronsted acidic conditions, the hemiaminals readily eliminated to generate a tetraene, while under basic conditions, the tetraol either decomposed or epimerized to generate a mixture of diastereomers. It is speculated that the base-mediated epimerization proceeds through ring-chain tautomerization involving a putative alpha-keto amide derivative. It is also of note that simple dissolution of tetraol (+)-95 in methanol also leads to its degradation to a complex mixture of products. 

Studies also show that by using catalyst 76a or 78 derived from one single chiral tetraol with the same absolute configuration, both enantiomers of the Diels-Alder reaction product can be obtained. For example, reaction of 2-methyl-... 

Novel macrobicyclic compounds have been prepared (151) from the tetraol obtained on de-O-benzylidenation of the bisgalactosido-18-crown-6 derivative aa-DD-117 in Figure 18. Selective tritylation of the two hydroxymethyl groups of the tetraol, followed by a base-promoted reaction with pentaethylene glycol ditosylate afforded aa-DD-155 with a polyether chain bridging the 4 and 4 positions of the D-galactopyranosidic rings across presumably the /3 face of the molecule. 

Dixon reported that saturated BINOL 45 sufficiently activates various N-Boc aryl imines toward Mannich reaction with acetophenone-derived enamines to yield P-amrno aryl ketones in good yields and enantioselectivities (Scheme 5.62) [116]. The same group applied a BINOL-derived tetraol catalyst to the addition of meth-yleneaminopyrroHdine to N-Boc aryl imines. Interestingly, appendage of two extra diarymethanol groups to the BINOL scaffold resulted in a marked increase in enantiomeric excess [117]. 

Coriolin (689), a metabolite of the Basidiomycete Coriolus consors, has attracted widespread interest because of its unusual anti-tumor activity and highly functionalized triquinane structure. Accordingly, a number of syntheses of689 have appeared on the scene. One of the earliest, due to Tatsuta, et al., begins with epoxide 690, whose preparation had been earlier realized in connection with their work on hirsutine (see Scheme LXIII). Deoxygenation of 690, hydrolysis, and cis-hydroxy-lation provided keto triol 691 (Scheme LXXII) The derived acetonide was transformed via 692 into tetraol 693 which could be selectively acetylated and dehydrated on both flanks of the carbonyl group. Deacetylation of 694 followed by epoxidation completed the synthesis. 

The pairwise additivity principle when applied to bichromophoric exciton-coupled systems, such as those composed of 4-bromobenzoate (BB) and 4-methoxycinnamate (MC) derivatives of cyclic polyols, yields more information from the CD spectra of complex molecules173. In such systems both degenerate ( homo") interactions, i.e., BB/BB and MC/MC, and nondegenerate ("hetero") interactions, i.e., BB/MC, contribute to the exciton CD spectra. As the homo exciton Cotton effects arc well separated (BB 236/253 nm, MC 287/322 nm) a unique pattern of CD curves is obtained for each derivative of cyclic tri- or tetraol. This method is particularly useful in identification of glycopyranosides174, a procedure essential for microscale structure determination of oligosaccharides by the exciton chirality method175. 

The phosphate derivatives (301)-(303) of 6-0-(2-hydroxyethyl)cyclohexane-l,2,4,6-tetraol have been synthesized as inositol monophosphatase inhibitors, the putative target for lithium therapy.270 Compounds (303) and (302) are the most potent examples of a primary alkyl phosphate and phosphate monanion inhibitor so far reported. 

The same authors described the synthesis of 2-deoxy thietanose 85 (Equation 27) <1996TL7569>. The reaction of a tetraol 83 derivative with sodium sulfide led to the bis-O-protected thietanose 84 in 62% yield subsequent treatment of compound 84 with />-toluenesulfonic acid followed by acylation with benzoyl chloride provided di-0,0-benzoyl thietanose 85 in 59% yield (Equation 26) <1996TL7569>. 

C. Uchida, H. Kimura, and S. Ogawa, Potent glycosidase inhibitors, IV-phenyl cyclic isourea derivatives of 5-amino- and 5-amino-l-C-(hydroxymethyl)-cyclopentane-l,2,3,4-tetraols, Bioorg. Med. Chem. Lett., 4 (1994) 2643-2648. 

As shown above, asymmetric catalysis of Diels-Alder reactions has been achieved by use of chiral titanium complexes bearing chiral diol ligands. Yamamoto has reported a chiral helical titanium complex derived from Ti(OPr )4 and a BINOL-derived tetraol ligand (Sch. 54) [134], The Diels-Alder products are obtained with uniformly high enantioselectivity, irrespective of the substituent pattern of a,/3-unsaturated aldehydes. Corey has also reported a new type of chiral titanium complex derived from an amino alcohol ligand (Sch. 55) [135]. The chiral titanium complex serves as an efficient asymmetric catalyst for the reaction of 2-bromoacrolein the Diels-Alder product is obtained with high enantioselectivity. 

The coupling reaction of epoxide 69 with the anion derived from the allyl sulfide 57, a system derived from geraniol, was accomplished in a 99% yield by employing 4 equivalents of the anion (Scheme 13). Protection of the alcohol as the MOM ether (95%), followed by debenzylation and removal of the phenylthio group under Birch conditions (76%) gave diene 70. Vanadium catalyzed oxidation and spontaneous cyclization of 70 imder acidic conditions afforded a diastereomeric mixture of tetraols 71 and 72 in 61% and 14% yields, respectively. 

Polycondensation of a corresponding tetraol compound derived from D-mannitol with a bisboric acid compound produces polymer 137.239 The Mw of the... 

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