An Efficient Transformation of (-)-Quinic Acid into Carba-l-rhamnose

Abstract

A novel stereoselective synthesis of carba-l-rhamnose from (-)-quinic acid is described. The title compound is obtained with an appropriate pattern of protecting groups to be used for the preparation of Streptococcus pneumoniae type 19F capsular polysaccharide repeating unit.

carba-l-rhamnose - stereoselective synthesis - capsular polysaccharide - quinic acid - shikimic acid

References

1a Fedson DS. Anthony J. Scott G. Vaccine  1999,  17:  S11 

1b Poland GA. Vaccine  1999,  17:  1674 

2a Jones C. Carbohydr. Eur.  1998,  21:  10 

2b Musher DM. Clin. Infect. Dis.  1991,  14:  801 

3 See for example: Austrian R. Vaccine  2001,  19:  S71 

4 See for example: Arndt B. Porro M. In Immunobiology of Proteins and Peptides VI   Atassi MZ. Plenum Press; New York: 1991.  p.129 

5 Redlich H. Sudau W. Szadenings AK. Vollerthun R. Carbohydr. Res.  1992,  226:  57 

6a Gaunt MJ. Yu J. Spencer JB. J. Org. Chem.  1998,  63:  4172 

6b Wright JA. Yu J. Spencer JB. Tetrahedron Lett.  2001,  42:  4033 

6c Xia J. Abbas SA. Locke RD. Piskorz CF. Alderfer JL. Matta KL. Tetrahedron Lett.  2000,  41:  169 

6d Liao W. Locke RD. Matta KL. Chem. Commun.  2000,  369 

6e Xia J. Alderfer JL. Piskorz CF. Matta KL. Chem.-Eur. J.  2001,  7:  356 

7 Bianco A. Brufani M. Manna F. Melchioni C. Carbohydr. Res.  2001,  332:  23 

8 Fernández S. Díaz M. Ferrero M. Gotor V. Tetrahedron Lett.  1997,  38:  5225 

9 Wang Z.-X. Miller SM. Anderson OP. Shi Y. J. Org. Chem.  2001,  66:  521 

10 Lautens M. Stammers TA. Synthesis  2002,  1993 

11 Marshall JA. Bourbeau MP. Org. Lett.  2002,  4:  3931 

12 Bessodes M. Shamsazar J. Antonakis K. Synthesis  1988,  560 

13

All new compounds have been characterized by proton and carbon NMR, exact mass, and/or elemental analysis. Spectroscopic data for selected compounds:
5a-Carba-2,3- O -cyclohexylidene-1- O -naphtylmetyl-α- l-rhamno-pyranoside ( 11a): ¹H NMR (300 MHz, CDCl₃): δ = 1.05 (d, 3 H, J _Me,5 = 6.0 Hz, Me), 1.30-1.80 (m, 12 H,
H-5a and 5 CH₂), 1.80-2.00 (m, 1 H, H-5), 3.30 (dd, 1 H, J _3,4 = 7.7 Hz, J _4,5 = 9.9 Hz, H-4), 3.90 (br m, 1 H, H-1), 4.05 (dd, 1 H, J _2,3 = 5.8 Hz, J _3,4 = 7.7 Hz, H-3), 4.29 (br m, 1 H, H-2), 4.72 and 4.78 (ABq, 2 H, CH₂-Nap), 7.20-7.90 (m, 7 H, Ar H). ¹³C NMR (75.4 MHz, CDCl₃): δ = 18.21 (q, CH₃), 23.81 (t), 24.17 (t), 25.13 (t), 30.06 (d, C-5), 32.60 (t), 35.41 (t), 38.10 (t), 71.32 (t), 74.15 (d), 76.71 (d), 78.12 (d), 80.22 (d), 109.74 (s), 125.99 (d), 126.24 (d, 2 C), 127.79 (d), 127.96 (d), 128.31 (d, 2 C), 133.09 (s), 133.37 (s), 135.77 (s). [α]_D ²⁵ +15.7 (c = 1, CHCl₃). Mp 99.0-101.0 °C.
5a-Carba-1-naphtylmetyl-3,4-dibenzyl-α- l-rhamno-pyranoside (14a,b): ¹H NMR (300 MHz, CDCl₃): 1.10 (d, 3 H, J _6,5 = 6.6 Hz, H-6), 1.62 (dt, 1 H, J _5aA,5aB = J _5aA,5 = 14.5 Hz, J _5aA,1 = 2.5 Hz, H-5aA), 1.86 (dt, 1 H, J _5aA,5aB = 14.5 Hz, J _5aB,5 = J _5aB,1 = 2.7 Hz, H-5aB), 1.97-2.17 (m, 1 H, H-5), 2.58 (br s, 1 H, -OH), 3.39 (t, 1 H, J _3,4 = J _4,5 = 9.1 Hz, H-4), 3.80 (br m, 1 H, H-1), 3.86 (dd, 1 H, J _2,3 = 3.3 Hz, J _3,4 = 9.1 Hz, H-3), 4.19 (br t, 1 H, H-2), 4.55-5.00 (m, 6 H, 3 ABq, CH₂-Nap and CH₂-Bn), 7.10-8.00 (m, 17 H, Ar H). ¹³C NMR (75.4 MHz, CDCl₃): δ = 18.34 (q, C-6), 31.78 (d,
C-5), 32.05 (t, C-5a), 69.74 (d), 71.20 (t), 72.69 (t), 75.43 (t), 76.16 (d), 82.33 (d), 83.32 (d), 125.71 (d), 125.96 (d), 126.15 (d), 126.25 (d), 127.64 (d), 127.83 (d), 127.92 (d), 127.99 (d), 128.02 (d, 2 C), 128.13 (d, 2 C), 128.24 (d), 128.47 (d, 2 C), 128.60 (d, 2 C), 133.08 (s), 133.40 (s), 136.20 (s), 138.51 (s), 139.14 (s). [α]_D ²⁵ -18.3 (c = 1, CHCl₃).

14 Takahashi T. Kotsubo H. Iyobe A. Namiki T. Koizumi T. J. Chem. Soc., Perkin Trans. 1  1990,  3065 

15

The stereochemistry of compounds 11a and 11b was inferred from the coupling constants of the signal of H-C(4) in ¹H NMR spectrum. In fact, H-C(4) appeared as a doublet of doublets for both compounds, but in 11a the ³ J were 7.7 Hz and 9.9 Hz, while in compound 11b the constants were 10.8 Hz and 3.2 Hz. Furthermore, H-C(4) in compound 13 appeared as a triplet with a ³ J of 9.9 Hz, clearly indicating the axial orientation of H-C(4) in a chair conformation of 13.

16 Shing TKM. Cui Y. Tang Y. Tetrahedron  1992,  48:  2349 

17 David S. Hanessian S. Tetrahedron  1985,  41:  643