Hemiketal

Hemiketal (Section 17 8) A hemiacetal derived from a ketone Henderson-Hasselbalch equation (Section 19 4) An equa tion that relates degree of dissociation of an acid at a partic ular pH to its... 

The hemiketal products (11) and (12) have been converted to the corresponding oximes, hydra2ones, and substituted amines (40,41). Although many of these derivatives exhibit substantial antibacterial activity, they are generally less active than the parent tetracyclines. 

Palytoxin carboxylic acid, C,23H2i3N053 (Figure 1, R -R = H), derived from palytoxin, C,29H223N3054, contains 41 hydroxyl groups, one amino group, one ketal, one hemiketal, and one carboxylic acid, in addition to some double bonds and ether linkages. 

This order was chosen so that DDQ (dichlorodicyanobenzoquinone) treatment would not oxidize a dep otected allylic alcohol at C.73, and so that the C.47 hemiketal would still be protected (as the ketal) during basic hydrolysis (step 3). 

Aldehydes and ketones undergo reversible addition reactions with alcohols. The product of addition of one mole of alcohol to an aldehyde or ketone is referred to as a hemiacetal or hemiketal, respectively. Dehydration followed by addition of a second molecule of alcohol gives an acetal or ketal. This second phase of the process can be catalyzed only by acids, since a necessary step is elimination of hydroxide (as water) from the tetrahedral intermediate. There is no low-energy mechanism for base assistance of this... 

The equilibrium constants for addition of alcohols to carbonyl compounds to give hemiacetals or hemiketals show the same response to structural features as the hydration reaction. Equilibrium constants for addition of metiianoHb acetaldehyde in both water and chloroform solution are near 0.8 A/ . The comparable value for addition of water is about 0.02 The overall equilibrium constant for formation of the dimethyl acetal of... 

The second step in acetal and ketal hydrolysis is conversion of the hemiacetal or hemiketal to the carbonyl compound. The mechanism of this step is similar to that of the first step. Usually, the second step is faster than the initial one. Hammett a p plots and solvent isotope effects both indicate that the transition state has less cationic character than... 

Disconnection of easily formed rings such as lactone, hemiketal or hemiacetal embedded in the skeleton but in a non-central location. 

As with isolated rings, individual heterorings in fused systems which are synthetic equivalents of acyclic subunits, e.g. lactone, ketal, lactam, and hemiketal, can be disconnected. 

Various combinations of Rf and R (equation 36) have been studied [39, 72, 73, 74, 75], and it appears that the stability of the lithium salt of the hemiketal is the major factor in determming the reaction products formed via paths A, B, or C in equation 37 Other important factors that affect the course of the reacbon are (1) thermal stability of the perfluoroalkyllithium compounds, (2) reaction temperature, (3) mode of addition of the reactants, (4) stenc hindrance, (5) nature of the Y group (in equation 36), and (6) temperature at which the reaction is terminated by acid hydrolysis... 

Certain fluorine compounds may be used to dehydrate nonfluorinated alcohols through their complexes or derivatives With aleohols, 1,1,1-trichlorotri-fluoroacetone forms intermediate hemiketals that easily decompose to olefins in the presence of a catalytic amount of p toluenesulfomc acid [S5] Similarly, the... 

Hemiketal (Section 17.8) A hemiacetal derived from a ketone. 

In a similar manner, ketones can react with alcohols to form hemiketals. The analogous intramolecular reaction of a ketose sugar such as fructose yields a cyclic hemiketal (Figure 7.6). The five-membered ring thus formed is reminiscent of furan and is referred to as a furanose. The cyclic pyranose and fura-nose forms are the preferred structures for monosaccharides in aqueous solution. At equilibrium, the linear aldehyde or ketone structure is only a minor component of the mixture (generally much less than 1%). 

FIGURE 7.16 Acetals and ketals can be formed from hemiacetals and hemiketals, respectively. 

The sluggishness of the reaction of TIPSOTf with tertiary alcohols can be exploited to advantage, as was the case in Magnus synthesis of strychnine. The equilibrium favors the tertiary hemiketal, but silylation favors the primary alcohol. 

As in the case of the steroids, introduction of additional nuclear substituents yields morphine analogs of increased potency. The more important of these are derived from one of the minor alkaloids that occur in opium. Thebaine (14), present in crude opium in about one-tenth the amount of morphine, exhibits a reactive internal diene system that is well known to undergo various addition reactions in a 1,4 manner (e.g., bromination). Thus, reaction with hydrogen peroxide in acid may be visualized to afford first the 14-hydroxy-6-hemiketal (15). Hydrolysis yields the isolated unsaturated ketone (16). Catalytic reduction... 

To a stirred solution of 4.6 g (0.01 mol) of anhydrous oxytetracycline in 40 ml of dry tetrahydrofuran is added 3.5 g (0.021 mol) of pyridine-sulfur trioxide complex. After 16 hours of stirring at room temperature, the resulting suspension is filtered, and the solid is slurried with 25 ml of 2% hydrochloric acid for 10 minutes, filtered and thoroughly washed with methanol followed by ether. The pale yellow crystalline 5-oxytetracycline-6, 12-hemiketal-12-sulfuric acid ester melts at 210°C. 

Heat of combustion, 113 Heat of hydrogenation, 186 table of, 187 Heat of reaction, 154 Helicase, DNA replication and, 1106 Hell-Volhard-Zelinskii reaction, 849 amino acid synthesis and. 1025 mechanism of, 849 Heme, biosynthesis of, 966 structure of, 946 Hemiacetal, 717 Hemiketal, 717 Hemithioacetal, 1148 Henderson-Hasselbalch equation,... 

When y-lactone 14 is treated with methylmagnesium bromide in THF at -78 °C, a carbonyl addition reaction takes place and gives, after aqueous workup, a hemiketal that is subsequently converted to... 

As inert as the C-25 lactone carbonyl has been during the course of this synthesis, it can serve the role of electrophile in a reaction with a nucleophile. For example, addition of benzyloxymethyl-lithium29 to a cold (-78 °C) solution of 41 in THF, followed by treatment of the intermediate hemiketal with methyl orthoformate under acidic conditions, provides intermediate 42 in 80% overall yield. Reduction of the carbon-bromine bond in 42 with concomitant -elimination of the C-9 ether oxygen is achieved with Zn-Cu couple and sodium iodide at 60 °C in DMF. Under these reaction conditions, it is conceivable that the bromine substituent in 42 is replaced by iodine, after which event reductive elimination occurs. Silylation of the newly formed tertiary hydroxyl group at C-12 with triethylsilyl perchlorate, followed by oxidative cleavage of the olefin with ozone, results in the formation of key intermediate 3 in 85 % yield from 42. 

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