Hydroxy and Hydroperoxy Acids

Saturated Hydroxy and Acetoxy Compounds

Tulloch et al.and Maazurek  [1] have reported NMR spectra for most of the regioisomeric hydroxy- and acetoxy-stearates. The CHOH or CHOAc group has a considerable effect on the chemical shifts of nearby carbon atoms as indicated below. These values are changes in shift from the normal value of 29.65 ppm for mid-chain CH2 groups (Table 1).

Table 1
XCHXαβγδεζ
OH +42.2 +7.8 -4.0 +0.06 -0.06 -0.09 -0.05
OAc +44.7 +4.4 -4.4 -0.20 -0.20 -0.10 -0.05

Isbell and Mund [2] reported the 13C-NMR spectrum of 5-hydroxyeicosanoic acid (C20) and several of its ethers.

 

Unsaturated Mono-hydroxy Acids

Unsaturated hydroxy acids with the structural unit -

-CH2CH2CH(OH)(CH2)nCH=CHCH2-

where n = 0, 1, or 2 have been examined and the results are summarised in Table 4 below. Additional data for some diacetoxy 18:4 esters [7] and some aken-1-ols [8] can be obtained from the references given. Pfeffer et al. [6] concluded that the effect of the OH function on nearby olefinic carbon shifts was as follows (values for n = 0 were calculated by the compiler). The values cited are to be added to or subtracted from the chemical shifts normally associated with a double bond in the appropriate position.

n = 0 cis 2.1 (β) and 2.9 (γ)
n = 0 trans 1.6 (β) and 2.9 (γ)
n = 1 cis 3.08 (γ) and -4.63 (δ)
n = 1 trans 4.06 (γ) and -4.18 (δ)
n = 2 cis -0.73 (δ) and 0.73 (ε)

Lie Ken Jie and Cheng [9] have provided chemical shifts (ppm) for a range of homoallylic and bis-homoallylic esters based on methyl ricinoleate (12-OH 9c-18:1) and methyl isoricinoleate (9-OH 12c-18:1) where the functional group is hydroxy, acetoxy, chloro, azido, or oxo (Table 5 below).

Chemical shifts (ppm) for a range of oxylipins (hydroxy unsaturated C20 acids and esters) are listed by Jiang and Gerwick [10].

Dihydroxy Acids

Data presented by Rakoff et al. [4] for threo and erythro saturated and unsaturated acids are given in Table 6 below. The threo and erythro isomers are distinguishable by their NMR spectra, particularly by the chemical shifts of CH2 groups α and β to the diol unit. The chemical shifts for 7,10-dihydroxystearic acid given by Knothe et al.  [11] have been assigned by the compiler.

Hydroperoxy and Other Oxidized Acids

Neff et al. [12] and Frankel et al. [13] have examined the NMR spectra of mono-, bis-, and tris-hydroperoxy esters produced during autoxidation of trilinolein and trilinolenin. Chemical shifts (ppm) for the carbon atoms α and β to the OOH group are given below. These, presumably, relate to the structural unit (Table 2):

Table 2 formula
 Trilinolein Trilinolenin
 monobistrismonobistris
α 86.4 86.4 86.6 86.7 87.0-88.0 87.0-88.0
β 25.0 25.0 25.0 24.84 25.51 25.58

 

Frankel et al. [13,14] have given chemical shifts for two stereoisomers of the 9-hydroperoxy 10,12-hydroperoxide (Table 3).

Table 3
Carbon atom8910111213
Isomer a 33.5 83.3 81.3 42.4 72.5 33.9
Isomer b 32.0 84.1 82.0 42.5 73.0 32.9

In a more recent study, Silwood and Grootveld [30] reported some 13C chemical shifts for glycerol esters containing 9-OOH 10t,12c-18:2 (86.0, 132.5, 131.0, 130.0, and 132.0 for C9-13, respectively) and 9-OOH 10t,12t-18:2 (87.5, 132.5, 133.0, 130.0, and 131.0 for C9-13, respectively) and for the aldehyde carbon atom in alkanals (201.0 ppm), 2t-alkenals (193.2 ppm), 2t,4t-alkadienals (191.5 ppm), and 2c,4t-alkadienals (192.8 ppm).

 

Primary Alcohols and Hydroperoxides

Bascetta and Gunstone [8] examined a series of primary alcohols (RCH2OH) and hydroperoxides (RCH2OOH) with 8-18 carbon atoms. Chemical shifts for the C18 compounds are listed in Table 6 below. They concluded that the influence of the CH2X group on the α (C2) and β (C3) carbon atoms is +3.34 and –3.69 for the CH2OH and –1.89 and –3.58 for the CH2OOH group relative to the CH2 group at 29.30.

 

Additional Material

Knothe et al. [15-18] have studied the allylic oxidation of olefinic alcohols, acids, and esters of varying chain length with selenium dioxide to produce a wide variety of mono- and dihydroxy olefinic compounds that can be hydrogenated to their saturated derivatives. These compounds contain the structural units -

–CH(OH)CH=CH-   and   -CH(OH)CH=CHCH(OH)-

- and their dihydro derivatives. A lot of 13C-NMR data have been reported but the original papers must be consulted for details. Kuklev et al. [19] have provided information on hydroxy dienoic acids (9- and 13-HODE).

Hou and others, studying the microbial oxidation of oleic and other unsaturated acids, have isolated and identified several unsaturated hydroxy acids for which they have reported 13C-NMR shifts. These include the following C18 acids some of which are included in Table 4:

10-hydroxy 8t-18:1 [20]; 10-hydroxy 12c-18:1 [21]; 10-hydroxy 6c,12c-18:2 [22]; 10-hydroxy 12c,15c-18:2 [22]; 7-hydroxy-17-oxo 9c-18:1 [23]; 7-hydroxy-16-oxo 9c-18:1 [24]; 7,10-dihydroxy 8t-18:1 [25]; 7,10-dihydroxy 18:0 [11]; 7,10,12-trihydroxy 8t-18:1 [26]; 12,13,17-trihydroxy 9c-18:1 [27], 12,13-dihydroxy 10t-18:1 [28], and the acetylenic compounds 8-hydroxy 9a,11t-18:2 and 8,11-dihydroxy 9a-18:1 [29].

Tables 4 to 6

Table 4. Chemical shifts (ppm) for unsaturated hydroxy acids containing the structural unit
-CH2CH2CH(OH)(CH2)nCH=CHCH2-    where n = 0, 1, or 2.
 nCH2·CH2CH(OH)CH2CH2CH=CHCH2Ref

  cis isomers

9-OH 10c 0   37.6 67.8 - - 132.1, 132.8 27.6 3
12-OH 10c 0   37.6 67.5 - - 131.9, 132.8 27.7 3
12-OH 9c 1 25.8 37.0 71.6 35.5 - 133.0, 125.5 27.4 4
10-OH 12c 1   36.6 71.2 35.2 - 125.1, 132.9 27.2 5
10-OH 12c,15c 1   36.7 71.2 35.2 - 131.9, 125.4 24.7a 5
9-OH 12c 2 25.50 37.36 71.71 37.46 23.60 129.19, 130.69 27.23 6
10-OH 6c 2 25.64 37.22 71.43 37.54 23.53 129.65, 129.85 26.75 6
9-OH 5c 2 25.70 37.24 71.51 37.75 23.55 129.09, 130.55 26.56 6

trans isomers

9-OH 10t 0   37.4 73.2 - - 132.1, 133.2 32.1 3
12-OH 10t 0   37.4 73.1 - - 131.9, 133.3 32.2 3
12-OH 9t 1 25.7 36.9 71.2 40.9 - 134.4, 126.2 32.7 4

a
= 126.7 (C15) 130.9 (C16).
These assignments are listed so that the CH(OH) and CH=CH chemical shifts lie in the same vertical column. CH2 groups between these two are absent when there is a. Other carbon atoms can be identified from these fixed points. For example in the entry for 12-OH 9c the shifts given relate to C14 to C8. Some of these values may also be influenced by acid/ester or methyl end groups. The compiler of this information has made or adjusted some of the assignments.
Table 5. Chemical shifts (ppm) for methyl ricinoleate (12-OH 9c-18:1) and isoricinoleate (9-OH 12c-18:1) [9a]
 ricinoleateisoricinoleate
C-1 174.343 174.355
C-2 34.093 34.089
C-3 24.937 24.918
C-4 a a
C-5 a a
C-6 a a
C-7 a 25.571
C-8 27.389 37.325
C-9 133.217 71.678
C-10 125.280 37.432
C-11 35.377 23.604
C-12 71.514 129.184
C-13 36.874 130.654
C-14 25.743 27.210
C-15 a a
C-16 31.866 31.538
C-17 22.641 22.588
C-18 14.100 14.080

a = unassigned values between 28.829 and 29.463.
Information is also given in the original paper for derivatives of these two esters in which the OH group is replaced by N3, OAc, Cl, and oxo functions.
Table 6. Chemical shifts (ppm) for selected hydroxy and hydroperoxy C18 compounds
 1234567
1         177.6 62.81 76.89
2         34.9 32.71 27.32
3         26.1 25.64 25.67
4         30.3 28.71 29.41
5         26.8 29.55 29.41
6         38.3 29.55 29.41
7 26.0 25.6     72.3 29.55 29.41
8 31.3 33.7 27.4 32.7 34.4 29.55 29.41
9 74.8 74.6 25.1 26.1 34.9 29.55 29.41
10 74.8 74.6 33.0 33.9 72.4 29.55 29.41
11 31.3 33.7 31.8 37.2 38.5 29.55 29.41
12 26.0 25.6 74.0 74.0 26.5 29.55 29.41
13     73.9 73.8 30.9 29.55 29.41
14     33.7 33.7 30.8 29.55 29.41
15     25.4 25.5 30.4 29.55 29.41
16         33.1 31.80 31.67
17         23.7 22.55 22.40
18         14.5 13.92 13.77
 
where 1 methyl erythro-9,10-dihydroxystearate [4]
  2 methyl threo-9,10-dihydroxystearate [4]
  3 methyl threo-12,13-dihydroxy-cis-9-octadecenoate [4]
  4 methyl threo-12,13-dihydroxy-trans-9-octadecenoate [4]
  5 7,10-dihydroxystearic acid [11]
  6 octadecan-1-oleic [8]
  7 octadecane-1-hydroperoxide [8]
 

References

  1. Tulloch, A.P. and Maazurek, M. 13C Nuclear magnetic resonance spectroscopy of saturated, unsaturated, and oxygenated fatty acid methyl esters. Lipids, 11, 228-234 (1976).
  2. Isbell, T.A. and Mund, M.S. Synthesis of secondary ethers derived from meadowfoam oil. J. Am. Oil Chem. Soc., 75, 1021-1029 (1998).
  3. Frankel, E.N., Garwood, R.F., Khambay, B.P.S., Moss, G.P. and Weedon, B.C.L. Stereochemistry of olefin and fatty acid oxidation (3) The allylic hydroperoxides from the autoxidation of methyl oleate. J. Chem. Soc., Perkin Transactions 1, 2233-2240 (1984).
  4. Rakoff, H., Weisleder, D. and Emken, E.A. 13C Nuclear magnetic resonance of mono- and dihydroxy saturated and unsaturated fatty methyl esters. Lipids, 14, 81-83 (1979).
  5. Koritala, S. and Bagby, M.O. Microbial conversion of linoleic and linolenic acids to unsaturated hydroxy fatty acids. J. Am. Oil Chem. Soc., 69, 575-578 (1992).
  6. Pfeffer, P.E., Sonnet, P.E., Schwartz, D.P., Osman, S.F. and Weisleder, D. Effects of bis homoallylic and homoallylic hydroxyl substitution on the olefinic 13C resonance shifts in fatty acid methyl esters. Lipids, 27, 285-288 (1992).
  7. Solem, M.L., Jiang, Z.D. and Gerwick, W.H. Three new and bioactive icosanoids from the temperate red alga Farlowia mollis. Lipids, 24, 256-260 (1989).
  8. Bascetta, E. and Gunstone, F.D. 13C Chemical shifts of long-chain epoxides, alcohols and hydroperoxides. Chem. Phys. Lipids, 36, 253-261 (1985).
  9. Lie Ken Jie, M.S.F. and Cheng, K.L. Nuclear magnetic resonance spectroscopic analysis of homoallylic and bis homoallylic substituted methyl fatty ester derivatives. Lipids, 30, 115-120 (1995).
  10. Jiang, Z.-D. and Gerwick, W.H. Novel oxylipins from the temperate red alga Polyneura latissima: evidence for an arachidonate 9(S)-lipoxygenase. Lipids, 32, 231-235 (1997).
  11. Knothe, G., Bagby, M.O., Peterson, R.E. and Hou, C.T. 7,10-Dihydroxy-8(E)-octadecenoic acid: stereochemistry and a novel derivative, 7,10-dihydroxyoctadecanoic acid. J. Am. Oil Chem. Soc., 69, 367-371 (1992).
  12. Neff, W.E., Frankel, E.N. and Miyashita, K. Autoxidation of polyunsaturated triacylglycerols. I. Trilinoleoylglycerol. Lipids, 25, 33-39 (1990).
  13. Frankel, E.N., Neff, W.E. and Miyashita, K. Autoxidation of polyunsaturated triacylglycerols. II. Trilinolenoylglycerol. Lipids, 25, 40-47 (1990).
  14. Frankel, E.N., Weisleder, D. and Neff, W.E. Synthesis of a saturated hydroperoxy-cyclic peroxide. Chemical Communications, 766-767 (1981).
  15. Knothe, G., Bagby, M.O., Weisleder, D. and Peterson, R.E. Allylic mono-and di-hydroxylation of isolated double bonds with selenium dioxide-tert-butyl hydroperoxide. NMR characterization of long-chain enols, allylic and saturated 1,4-diols, and enones. J. Chem. Soc. Perkin Trans. 2, 1661-1669 (1994).
  16. Knothe, G., Weisleder, D., Bagby, M.O. and Peterson, R.E. Hydroxy fatty acids through hydroxylation of oleic acid with selenium dioxide/tert-butyl hydroperoxide. J. Am. Oil Chem. Soc., 70, 401-404 (1993).
  17. Knothe, G., Bagby, M.O., Weisleder, D. and Peterson, R.E. Allylic hydroxy fatty compounds with Δ5-, Δ7-, Δ8-, and Δ10-unsaturation. J. Am. Oil Chem. Soc., 72, 703-706 (1995).
  18. Knothe, G. and Bagby, M.O. Assignment of 13C nuclear magnetic resonance signals in fatty compounds with allylic hydroxy groups, J. Am. Oil Chem. Soc., 73, 661-663 (1996).
  19. Kuklev, D.V., Christie, W.W., Durand, T., Rossi, J.C., Vidal, J.P., Kasyanov, S.P., Akulin, V.N. and Bezuglov, V.V. Synthesis of keto and hydroxydienoic compounds from linoleic acid. Chem. Phys. Lipids, 125, 125-134 (1997).
  20. Kim, H., Gardner, H.W. and Hou, C.T. 10(S)-Hydroxy-8(E)-octadecenoic acid, an intermediate in the conversion of oleic acid to 7,10-dihydroxy-8-(E)-octadecenoic acid. J. Am. Oil Chem. Soc., 77, 95-99 (2000).
  21. Hou, C.T. Conversion of linoleic acid to 10-hydroxy-12(Z)-octadecenoic acid by Flavobacterium sp. (NRRL B-14859). J. Am. Oil Chem. Soc., 71, 975-978 (1994).
  22. Hou, C.T. Production of hydroxy fatty acids from unsaturated fatty acids by Flavobacterium sp. DS5 hydratase, a C-10 positional and cis unsaturation-specific enzyme. J. Am. Oil Chem. Soc., 72, 1265-1270 (1995).
  23. Lanser, A.C. Bioconversion of oleic acid by Bacillus strain NRRL BD-447: identification of 7-hydroxy-17-oxo 9-cis-octadecenoic acid. J. Am. Oil Chem. Soc., 76, 1023-1026 (1999).
  24. Lanser, A.C. Bioconversion of oleic acid to a series of keto-hydroxy and dihydroxy acids by Bacillus species NRRL BD-447: identification of 7-hydroxy-16-oxo 9-cis-octadecenoic acid. J. Am. Oil Chem. Soc., 75, 1809-1813 (1998).
  25. Hou, C.T., Bagby, M.O., Plattner, R.D. and Koritala, S. A novel compound, 7,10-dihydroxy-8-(E)-octadecenoic acid. J. Am. Oil Chem. Soc., 68, 99-101 (1991).
  26. Kuo, T.M., Manthey, L.K. and Hou, C.T. Fatty acid bioconversions by Pseudomonas aeruginosa PR3. J. Am. Oil Chem. Soc., 75, 875-879 (1998).
  27. Hou, C.T. A novel compound, 12,13,17-trihydroxy-9(Z)-octadecenoic acid, from linoleic acid by a new microbial isolate Clavibacter sp. ALA2. J. Am. Oil Chem. Soc., 73, 1359-1362 (1996).
  28. Lie Ken Jie, M.S.F. and Wong, K.P. Dehydration reactions involving methyl 9,12-dihydroxy-10-trans-octadecenoate. Chem. Phys. Lipids, 62, 177-183 (1992).
  29. Lie Ken Jie, M.S.F., Pasha, M.K. and Alam, M.S. Oxidation reactions of acetylenic fatty esters with selenium dioxide/tert-butyl hydroperoxide, Lipids, 32, 1119-1123 (1997).
  30. Silwood, C.J.L. and Grootveld, M. Application of high resolution, two dimensional 1H and 13C nuclear magnetic resonance techniques to the characterization of lipid oxidation products in autoxidized linoleoyl/linolenoylglycerols. Lipids, 34, 741-756 (1999).