Other Allo-Acids

Prior to the identification of /3-lagodeoxycholic acid this acid was prepared by Yukawa (35) and by Hofmann and Mosbach (36) from the key intermediate, V, by the Huang-Minlon reduction. Although this reduction is 

Additional substituent Method Yield 3a-ol 3p-ol Ratio 3a 3 3 Overall yield 

Hoshita et al. (39) reported the synthesis of this acid from anhydro-5a-cyprinol (26,27-epoxy-3o ,7a,12a-trihydroxy-5a-cholestane) (XV) as shown in Fig. 10. Kallner (66) and Ziller, Mitra, and Elliott (68,40) prepared the ester as described under A, 2 and A, 3 respectively. 

Goto (88) obtained an allo-acid designated as 3a,7 -dihydroxy-5a-cholanoic acid in a manner somewhat analogous to the procedure of Anderson and Haslewood for the preparation of allocholic acid. Methyl 3 -cathyl-7,12-diketo-6a-bromo-5/3-cholanoate was allomerized with alkali to provide three ketolic acids. One of these designated as 3a,7/3-dihydroxy-6,12-diketo-5a-cholanoic acid, m.p. 235 °C, was reduced by the Wolff-Kishner procedure to provide equal quantities of allocholanic acid and alloursodeoxycholic acid, m.p. 223-224°C. 

In a recent report Nakada et al. (89) detailed the preparation of 3,7-dioxo-5a-cholanoic acid (m.p. 185-187 °C) from 3 -hydroxy-7-keto-chol-5-enoic acid obtained from oxidation of 3/3-hydroxy-chol-5-enoic acid with CrOg and subsequent reduction. Reduction of this material should provide the 3jS-epimer of allochenodeoxycholic acid and its 7p-epimer. 

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The specific rotations of the acid and methyl ester are given in Table I with the solvent and concentration molecular rotations have been calculated for the methyl esters where specific rotations are available. Agreement between the calculated and found values is reasonably good for most substances. Although allolithocholic, allochenodeoxycholic, allodeoxycholic, and allo-cholic acids are less dextrorotatory than their corresponding 5 acids (65), the specific rotations of a number of the other allo-acids are either equivalent to or more dextrorotatory than the comparable 5 -epimer, thus precluding a general conclusion for this class of compounds. Optical rotatory dispersions of a few 3-keto-allo derivatives have been reported (34, 66, 67, 68, 40). 

The trans fusion of rings A and B in the allo-acids produces a more planar molecule than the 5 3 acid and contributes to the poorer detergency of glyco allodeoxycholate and consequent poorer solubility of the calcium salt (36). The Krafft point (critical micellar temperature) of several allo-acids has been determined and discussed (64). In contrast to the notorious character of deoxycholic acid to complex with a large variety of other substances, no evidence has been reported for the formation of choleic acids by allodeoxycholic acid. 

Because of the low yields attendant with this somewhat lengthy method, other procedures were investigated. Two general methods for the preparation of allo-acids have resulted. 

Support for the concept of an unsaturated intermediate in the formation of allo-acids is provided by recent experiments of Yamasaki et at. (98, 89). After administration of 3-ketochol-4-enoic-24- - C acid to rats and examination of the biliary metabolites, all four isomers of 3-hydroxycholanoic acid were identified other di- and trihydroxy acids were not investigated. Of the four possible 3-hydroxy-isomers about twice as much lithocholate was present as each of the other isomers. Similar results were obtained following administration of 3/3-acetoxychol-5-enoic-24-i- C acid in addition, 3f,6 -dihydroxy-5a-cholanoic acids were obtained. Yamasaki et al. (89) propose that a 3/3-dehydrogenase converts the 3/3-hydroxy-J -cholenoic acid to the a,/3-unsaturated ketone from which both 5 and 5 acids are derived, whereas hydroxylation of the above acid provides the diol from which only 5 acids are produced, somewhat analogous to the scheme of metabolism proposed by Mitropoulos and Myant (132) for the formation of chenodeoxycholic acid and the muricholic acids. 

The lantibiotic cypemycin isolated from a Streptomyces sxi21tl exhibits bis-methylation at Alai (Me2N-Ala) and an L- //o-isoleucine at position 13. The gene for its precursor peptide has not been reported, and hence the amino acid that is modified to generate the allo-We is not known. If it is introduced posttranslationally like all other modifications in lantibiotics, its most likely precursors would be either He or Leu and the posttranslational modification may involve a radical mechanism as neither amino acid is activated at C/3 or C7 for heterolytic chemistry. 

Almost all actinomycins have the same chromophore, a planar phenoxazinone dicarboxylic acid called actinociiL In dactinomycin, the structure of which is shown in Figure 12, the two pendent pentapeptide lactones are identical, but in other actinomycins these lactones may be different. In other actinomycins the first amino acid, amide linked with actinocin, is usually L-threonine, as in dactinomycin the second position is sometimes D-allo-isoleucine instead of D-valine the third position may be sarcosine or oxoproline the fourth position is sarcosine and the fifth position is sometimes iV-methyl isoleucine instead of N-methylvaline. The lactone ring is always present. 

Three stereoisomeric inositols were prepared from the highly functionalized derivative 215 which can be derived from 214 in one step by the reaction with KMn04 (Scheme 4-13).82 Treatment of 215 with AI2O3 in an aqueous medium afforded stereoselectively the ketoalcohol 216 in 85% yield, which was converted efficiently to allo-inositol (217) essentially as a single product. The epoxy diol 215 was converted under basic conditions to D-chiro-inositol (125) with more than 95% selectivity by attack of the hydroxide ion on one side of the epoxide carbon atom while its treatment under acidic conditions furnished neo-inositol (219) as a minor product along with 125 (3 7) resulting from the attack of H2O from the other side. 

Among the amino acids, threonine, hydroxylysine, cystine, isoleucine, the two hydroxyprolines, and others possess two optically active centers. Therefore, the synthetic compounds are mixtures of four diastereoisomers the l- and d- forms, and the L-allo- and D-allo- forms, respectively. For example, threonine can have these four forms L-threonine (XLI), D-threonine (XLII), L-allothreonine (XLIII), and D-allothreonine (XLIV). 

Examples of cases in which the amino acid and its alio form have spectra which differ from each other are threonine and allothreonine, hydroxyproline and allo-hydroxyproline, isoleucine and alloisoleucine, phenylserine and allophenylserine. 

Besides its value for jewelry currency, and electronics, gold is also important in the health professions. Because of its resistance to corrosion by acids and other substances foimd in saliva, gold is an ideal metal for dental crowns and caps, which accoimts for about 3% of the annual use of the element. The pure metal is too soft to use in dentistry, so it is combined with other metals to form allo. ... 

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