Diol activation

This section outlines three chemical transformations designed to allow further synthetic elaboration of the diols obtained from AD. The first and most broadly applicable method is the conversion of the diols into cyclic sulfates, a functionality that has reactive properties like an epoxide but is even more electrophilic than an epoxide [68]. The second approach to diol activation is the regioselective conversion of one of the hydroxyl groups into a sulfonate ester [69], This approach requires that the diol be substituted in a way that leads to regioselective derivatization of one of the two hydroxyl groups, and diol esters are a prime example of such... 

Epoxyactivation of agarose beads. Wash the required amount of Sepharose CL-6B with 40 mL of distilled water/g of gel on a sintered funnel (see Note 7). Transfer the washed agarose to a 1 L conical flask and add 1 mL of distilled water/g of gel. To this moist gel, add 0.8 mL of NaOH/mL of gel and incubate the slurry for 1 h at 25 C on a rotary shaker. Raise the temperature to 34°C and add 1 mL of epichlorohydrin/mL of gel to the reaction mixture (21). Wash the epoxide-activated resin with 40 mL distilled water/g of gel on a grade 2 sintered funnel and use it directly for >diol activation (Fig. 4 Resin B). Determine the epoxy-content according to Note 7. 

Cfr-diol activation. Treat the washed epoxy-activated gel with 1 mL of 5 M NaOH/mL of gel and stir overnight at 34°C. This base-catalyzed procedure gradually hydrolyses the epoxide ring resulting in the formation of a r-diol reaction product (Fig. 4 Resin C). 

Aldehyde functionalization. Treat the diol-activated resin with 2 mL of 0.1 M sodium periodate NalO /g of moist weight gel and leave to stir at 30°C for 3 h. This procedure causes the cleavage of the rw-diol, leaving a terminally functionalized aldehyde group (Fig. 4 Resin D). 

Several types of cyclic carbonates have been used in Pd(0) chemistry. They wiU be treated separately. Perhaps the most simple case is the cyclic carbonate of 2-methylene-l,3-diol (Scheme 43). Tsuji and co-workers " and Breuilles and Uguen used this compound to activate one alcohol function toward substitution while protecting the other. Note that dicarbonate of the same diol activates both alcohols (Scheme 42). 

Twerdok, L. E. Mosebrook, D. R. Trush, M. A. Comparison of oxidant-generation and BP-diol activation by bone marrow cells from C57B1/6 and DBA/2 mice implications for risk of bone marrow toxicity induced by polycyclic hydrocarbons. Toxicol. Appl. Pharmacol. 1992, 772, 266-272. 

The syntheses of brevicomin (67)[109,110] and frontalin[l 11] have been achieved as an elegant application of the intramolecular acetal formation with the diol 66 in dry DME. Optically active frontalin (68) has been synthesized by this cyclization in triglymejl 12]. 

Efficient acetalization of alkenes bearing various EWG with an optically active 1.3-diol 72 proceeds smoothly utilizing PdCN, CuCI. and O2 in DME to give the 1,3-dioxane 73[113], Methacrylamide bearing 4-t-butyloxazolidin-2-one 74 as a chiral auxiliary reacts with MeOH in the presence of PdCE catalyst... 

The 7, i5-unsaturated alcohol 99 is cyclized to 2-vinyl-5-phenyltetrahydro-furan (100) by exo cyclization in aqueous alcohol[124]. On the other hand, the dihydropyran 101 is formed by endo cyclization from a 7, (5-unsaturated alcohol substituted by two methyl groups at the i5-position. The direction of elimination of /3-hydrogen to give either enol ethers or allylic ethers can be controlled by using DMSO as a solvent and utilized in the synthesis of the tetronomycin precursor 102[125], The oxidation of the optically active 3-alkene-l,2-diol 103 affords the 2,5-dihydrofuran 104 in high ee. It should be noted that /3-OH is eliminated rather than /3-H at the end of the reac-tion[126]. 

One of the principal substances obtained from archaea (one of the oldest forms of life on earth) is denved from a 40 carbon diol Given the fact that this diol is optically active is it com pound A or is it compound... 

Pyrethroids from Chiysanthemic Acid. The unsaturated side chains of the aHethrolone alcohol moieties of the natural pyrethrins are readily epoxidized by microsomal oxidases and converted to diols, thus detoxifying the insecticides. Esterification of chrysanthemic acid (9), R = CH3, with substituted ben2yl alcohols produces usehil insecticides barthrin [70-43-9J, 2-chloro-3,4-methylenedioxyben2yl (+)-i7j ,/n7 j -chrysanthemate, and dimethrin [70-38-2] 2,4-dimethylben2yl (+)-i7j ,/n7 j -chrysanthemate. These have alimited spectmm of insecticidal activity but are of very low mammalian toxicity, ie, rat oralLD s >20,000 mg/kg. 

In contrast to the hydrolysis of prochiral esters performed in aqueous solutions, the enzymatic acylation of prochiral diols is usually carried out in an inert organic solvent such as hexane, ether, toluene, or ethyl acetate. In order to increase the reaction rate and the degree of conversion, activated esters such as vinyl carboxylates are often used as acylating agents. The vinyl alcohol formed as a result of transesterification tautomerizes to acetaldehyde, making the reaction practically irreversible. The presence of a bulky substituent in the 2-position helps the enzyme to discriminate between enantiotopic faces as a result the enzymatic acylation of prochiral 2-benzoxy-l,3-propanediol (34) proceeds with excellent selectivity (ee > 96%) (49). In the case of the 2-methyl substituted diol (33) the selectivity is only moderate (50). 

Lipase-catalyzed intermolecular condensation of diacids with diols results in a mixture of macrocycUc lactones and liuear oligomers. Interestingly, the reaction temperature has a strong effect on the product distribution. The condensation of a,(D-diacids with a,(D-dialcohols catalyzed by Candida glindracea or Pseudomonas sp. Upases leads to macrocycUc lactones at temperatures between 55 and 75°C (91), but at lower temperatures (<45°C) the formation of oligomeric esters predorninates. Optically active trimers and pentamers can be produced at room temperature by PPL or Chromobacterium viscosum Upase-catalyzed condensation of bis (2,2,2-trichloroethyl) (+)-3-meth5ladipate and 1,6-hexanediol (92). 

Dimethylhexane-2,5-diol [110-03-2] M 146.2, m 88-90. Purified by fractional crystn. Then the diol was dissolved in hot acetone, treated with activated charcoal, and filtered while hot. The soln was cooled and the diol was filtered off and washed well with cold acetone. The crystn process was repeated several times and the crystals were dried under a vac in a freeze-drying apparatus [Goates et al. J Chem Soc, Faraday Trans 1 78 3045 1982]. 

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