The tetrahydropyranyl-protected mandelic acid: A novel versatile chiral derivatising agent

Tetrahedron Asymmetry

Volumn 9, Issue 5, 1998, Pages 885-896

  Parve, Omar ^a   Aidnik, Madis ^b   Lille, Ülo ^a   Martin, Ivar ^a   Vallikivi, Imre ^a   Vares, Lauri ^a   Pehk, Tõnis ^c  

^a TALLINN UNIVERSITY OF TECHNOLOGY   (Estonia)

^b ESTONIAN UNIVERSITY OF LIFE SCIENCES   (Estonia)

^c NATIONAL INSTITUTE OF CHEMICAL PHYSICS AND BIOPHYSICS   (Estonia)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA METHOXY ALPHA (TRIFLUOROMETHYL)PHENYLACETIC ACID; MANDELIC ACID; TETRAHYDROPYRAN DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CHIRALITY; ENANTIOMER; METHODOLOGY; NUCLEAR MAGNETIC RESONANCE; PRIORITY JOURNAL; RACEMIC MIXTURE;

EID: 0032513166     PISSN: 09574166     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0957-4166(98)00053-6     Document Type: Article

References (47)

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2. 2. Trost, B. M.; Belletire, J. L.; Godleski, S.; McDougal, P. G.; Balkovec, J. M.; Baldwin, J. J.; Christy, M. E.; Ponticello, G. S.; Varga, S. L.; Springer, J. P. J. Org. Chem., 1986, 51, 2370-2374.
3. 3. Dale, J. A.; Dull, D. L.; Mosher, H. S. J. Org. Chem., 1969, 34, 2543-2549.
4. 4. Pehk, T.; Lippmaa, E.; Lopp, M.; Paju, A.; Borer, B. C.; Taylor, R. J. K. Tetrahedron: Asymmetry, 1993, 4, 1527-1532.
5. (a) Parker, D. Chem. Rev., 1991, 91, 1441-1457.
6. 5. Dale, J. A.; Mosher, H. S. J. Am. Chem. Soc., 1973, 95, 512-519.
7. 8 as being readily separable from diastereomeric impurities by crystallisation affording a simple way to diminish (gradually) the influence of the optical impurity of CDA on the enantiomeric excess of the target alcohol by introduction of two (or more) CDA molecules. See also Refs. 1 and 38.
8. 7. Whitesell, J. K.; Reynolds, D. J. Org. Chem., 1983, 48, 3548-3551.
9. (a) Parker, D. J. Chem. Soc., Perkin Trans. 2, 1983, 83-88.
10. 8. Whitesell, J. K.; Lawrence, R. M. CHIMIA, 1986, 40, 318-321.
11. f-s 0.314, 0.266, 0.238 were measured for three other isomeric products under the same conditions.
12. 10. Seebach, D.; Naef, R.; Calderari, G. Tetrahedron, 1984, 40, 1313-1324.
13. 11. Wissner, A.; Grudzinskas, C. V. J. Org. Chem., 1978, 43, 3972-3974.
14. 12. Our unpublished results.
15. 13. Newton, R. F.; Reynolds, D. P.; Webb, C. F.; Roberts, S. M. J. Chem. Soc., Perkin Trans. 1, 1981, 2055-2058.
16. 14. Mash, E. A.; Arterburn, J. B.; Fryling, J. A. Tetrahedron Lett., 1989, 30, 7145-7148.
17. 15. Mash, E. A.; Arterburn, J. B.; Fryling, J. A.; Mitchell, S. H. J. Org. Chem., 1991, 56, 1088-1093.
18. 16. Mash, E. A.; Fryling, J. A.; Wexler, P. A. Acta Cryst., 1991, C47, 2708-2709.
19. 4 (acetone, for instance) that could easily be evaporated prior to addition of n-hexane.
20. 19 The diastereomeric purity (∼99/1) was found to have remained practically unchanged during the alkaline treatment proving the occurrence of no detectable racemisation throughout the above procedures.
21. 19. The HPLC analysis of THPMA methyl esters was performed instead of that of free acids 3 and 4 because of the complications encountered on looking for HPLC conditions for the analysis of the latter which still remained unreliable in our hands.
22. 40 of known configuration. The individual diastereomer (8) of >99% diastereomeric purity (by HPLC) was obtained showing the high optical purity of (3) as well as the occurrence of undetectable racemisation throughout derivatisation. The assignment of 2-butanol esters (24), (25) is based on the NMR study and it fits nicely the systematic study of the regularities found in the MPA esters of homological secondary aliphatic alcohols from butanol to decanol.
23. 4), filtered and evaporated to afford crude THP-mandelates (8) and (9) which were purified over silica (eluent; benzene:EtOAc 98:2). The total yield of esters was 96.3% (408 mg).
24. 13C chemical shifts.
25. 23. Energy minimisations were carried out using a semi-empirical method: Austin Method 1 (AM 1), M. J.S. Dewar et al. J. Am. Chem. Soc., 1985, 107, 3902.
26. 24. Conformational space of 5 and 6 was scanned by using the DGEOM95 package (Chiron Corp.©95).
27. 6:EtOAc=10:1); 12/13: IR 3450/3460, Table 5
28. 13C NMR spectra of diastereomeric THPMA 3 esters of 2-butanol
29. 6:n-hexane:EtOAc 5:5:1); 35/36: for NMR data see Ref. 41
30. 26. Newton, R. F.; Paton, J.; Reynolds, D. P.; Young, S.; Roberts, S. M. J. Chem. Soc., Chem. Commun., 1979, 908-909.
31. 27. Parve, O.; Vallikivi, I.; Lahe, L.; Metsala, A.; Lille, Ü.; Tõugu, V.; Vija, H.; Pehk, T. Bioorg. Medicinal Chem. Lett., 1997, 7, 811-816.
32. 28. Parve, O.; Pals, A.; Kadarpik, V.; Lahe, L.; Lille, Ü.; Sikk, P.; Lõokene, A.; Välimäe T. Bioorg. Medicinal Chem. Lett., 1993, 3, 359-362.
33. 21 The diastereomers 8, 9 were obtained in the ratio of 53/47 by HPLC, while the remaining 7 had an specific rotation close to zero. Contrary to this, the above trial for (±)-26 proved the occurrence of some kinetic differentiation that was not studied further because the quantitative conversion of the starting alcohol took place in all derivatisations with 3.
34. 3:EtOH (99:1) for 21, 22.
35. 31. The Chromatographic separation of the diastereomers 10/11 and 12/13 has been studied. See: Lõhmus, M.; Parve, O.; Kanger, T.; Lopp, M.; Lille, Ü. Resolution of diastereomers as a key step in obtaining optically pure prostanoids In: Abstracts. The 13th Symp. of Column Liquid Chromatography. Stockholm, 1989, 47.
36. 4 (3:1) for 16 h.
37. 33. The alkaline hydrolysis was performed stirring the sample during 16 h in a MeOH:1 N NaOH (3:1) mixture.
38. 34. Newton, R. F. New Synthetic Routes to Prostaglandins and Thromboxanes; Roberts, S. M. and Sheinmann, F., Eds; Academic Press: London, 1982, pp. 61-104.
39. 35. MARTINDALE, The Extra Pharmacopoeia. Thirtieth Edition. Reynolds, J. E. F., Ed.; The Pharmaceutical Press: London, 1993, p. 1150.
40. 36. The sample of (±)-cloprostenol was kindly provided by Kemasol Ltd, Tallinn.
41. 2O (90:9.6:0.4) for 17.
42. 37. The optical resolution procedure was started from 100 mg of (±)-17: total yield 67%. The present process for the optical resolution of cloprostenol is supposed to allow a very high control of the enantiomeric purity of the product: the optical purity of the CDA (e.e.) was ≥98% and all minor diastereomers were separated by semipreparative HPLC (as concluded by HPLC and NMR analysis). Then the content of the enantiomeric contamination could be calculated as follows: 0.01×0.01×0.01×100%=0.0001%. The value calculated characterises the expected enantiomeric excess of the target enantiomeric cloprostenols to be as high as 99.9998%. This consideration should be proved by further analysis using proper methodologies. Compounds of a very high enantiomeric purity can also be obtained by using the repetition of any of the optical resolution procedure (see also Ref. 6).
43. 39. See Table 5.
44. 1H 1 74.05 2.42 73.90 2.34 74.20 2.45 74.04 2.36 2 80.27 - 80.08 - 80.15 - 79.95 -3 64.89 5.30 64.96 5.28 65.17 5.29 65.22 5.28 4 34.07 1.48 34.13 1.67 34.13 1.48 34.13 1.65 5 24.02 1.12 24.28 1.35 24.03 1.07 24.29 1.31 6 30.91 1.12 31.02 1.26 30.91 1.09 31.01 1.23 7 22.24 1.18 22.31 1.29 22.26 1.16 22.34 1.28 8 13.80 0.82 13.85 0.88 13.81 0.82 13.86 0.88 THP 2 96.46 4.66 96.34 4.65 - - - -3 30.07 1.73 30.07 1.74 - - - -4 18.70 1.55/1.96 18.72 1.55/1.96 - - - -5 25.24 1.57/1.59 25.24 1.57/1.59 - - - -6 61.92 3.45/3.94 62.94 3.47/3.94 - - - -CO′ 169.78 - 169.86 - 172.65 - 172.72 -CO″ 167.01 - 167.08 - 166.73 - 166.82 -α′ 76.28 5.38 76.22 5.38 72.86 5.32 72.93 5.51 α″ 74.71 5.99 74.67 5.97 75.53 6.01 75.58 5.98
45. 40. Hashimoto, S.; Kose, S.; Suzuki, A.; Yanagiya, Y.; Ikegami, S. Synth. Commun., 1991, 21, 833-839.
46. 41. See Table 6.
47. 42. See Table 7.