K. N. Fanning, A. Sutherland / Tetrahedron Letters 48 (2007) 8479–8481
8481
tion of allylic alcohols to the corresponding saturated
Acknowledgement
alcohol is a common transformation,11 examples of hy-
droxyl group reduction are also known.12 Fortunately,
the hydrogenation of allylic alcohol 13 with platinum
oxide as the catalyst did give saturated alcohol 15, after
optimisation, in an excellent 97% yield.
Financial support from the University of Glasgow is
gratefully acknowledged.
References and notes
The final stage of our synthesis of (S)-gizzerosine 1
required the coupling of histamine with an activated
intermediate of 6-hydroxynorleucine derivative 15. To
this effect, 15 was converted to mesylate 3 under stan-
dard conditions (Scheme 4). Subsequent reaction with
histamine in the presence of DBU gave coupled product
16 in 66% yield. Finally, acid mediated deprotection of
16 gave (S)-gizzerosine 1 in quantitative yield.13
1. Johnson, D. C.; Pinedo, C. Avian Dis. 1971, 15, 835–
837.
2. (a) Mori, K.; Okazaki, T.; Noguchi, T.; Naito, H. Agric.
Biol. Chem. 1983, 47, 2131–2132; (b) Okazaki, T.; Nogu-
chi, T.; Igarashi, K.; Sakagami, Y.; Seto, H.; Mori, K.;
Naito, H.; Masumura, T.; Sugahara, M. Agric. Biol.
Chem. 1983, 47, 2949–2952; (c) Mori, K.; Sugai, T.;
Maeda, Y.; Okazaki, T.; Noguchi, T.; Naito, H. Tetrahe-
dron 1985, 41, 5307–5311.
3. (a) Masumura, T.; Sugahara, M.; Noguchi, T.; Mori, K.;
Naito, H. Poultry Sci. 1985, 64, 356–361; (b) Sugahara,
M.; Hattori, T.; Nakajima, T. Agric. Biol. Chem. 1987, 51,
3423–3424; (c) Ito, Y.; Terao, H.; Noguchi, T.; Naito, H.
Poultry Sci. 1988, 67, 1290–1294.
OMs
OH
a
CO2Me
NHBoc
CO2Me
NHBoc
3
4. Shimasaki, Y.; Kiyota, H.; Sato, M.; Kuwahara, S.
Tetrahedron 2006, 62, 9628–9634.
5. Shimasaki, Y.; Kiyota, H.; Sato, M.; Kuwahara, S.
Synthesis 2005, 3191–3192.
15
b
H
N
H
N
´
´
6. (a) Padron, J. M.; Kokotos, G.; Martın, T.; Markidis, T.;
´
Gibbons, W. A.; Martın, V. S. Tetrahedron: Asymmetry
NH
NH
´
1998, 9, 3381–3394; (b) Kokotos, G.; Padron, J. M.;
N
N
c
´
´
Martın, T.; Gibbons, W. A.; Martın, V. S. J. Org. Chem.
CO2H
CO2Me
1998, 63, 3741–3744.
7. (a) Sutherland, A.; Caplan, J. F.; Vederas, J. C. Chem.
Commun. 1998, 555–556; (b) Adamczyk, M.; Johnson, D.
D.; Reddy, R. E. Tetrahedron: Asymmetry 2000, 11, 3063–
3068; (c) Cox, R. J.; Hadfield, A. T.; Mayo-Martin, M. B.
Chem. Commun. 2001, 1710–1711; (d) Cox, R. J.; Gibson,
J. S.; Martin, M. B. M. ChemBioChem 2002, 3, 874–886;
(e) Hamilton, D. J.; Sutherland, A. Tetrahedron Lett.
2004, 45, 5739–5741; (f) Cox, R. J.; Gibson, J. S.;
Hadfield, A. T. ChemBioChem 2005, 6, 2255–2260; (g)
Luzzio, F. A.; Duveau, D. Y.; Figg, W. D. Heterocycles
2006, 70, 321–334.
NH2
NHBoc
1
16
Scheme 4. Reagents and conditions: (a) CH3SO2Cl, NEt3, DMAP,
CH2Cl2, 86%; (b) histamine, DBU, MeOH, D, 66%; (c) 6 M HCl, D,
100%.
In summary, we have developed a simple, practical
approach for the synthesis of (S)-gizzerosine 1 in 10
steps and in 31% overall yield from L-aspartic acid 5.
This route utilised a Wittig reaction for the two-carbon
homologation of L-aspartic acid semi-aldehyde 4 that
was converted to 6-hydroxynorleucine derived mesylate
3 for efficient coupling with histamine 2. While some
problems were encountered in attempting the two-step
conversion of a,b-unsaturated aldehyde 9 to 6-hydroxy-
norleucine derivative 15, the optimised reactions involv-
ing sodium borohydride reduction of the aldehyde
followed by platinum oxide catalysed hydrogenation of
the alkene did allow this transformation to take place
in excellent yield. Finally, this approach has been used
specifically for the preparation of (S)-gizzerosine 1.
However, the substitution of histamine with other nucleo-
philes would lead to the late stage synthesis of a small
library of gizzerosine derivatives for biological testing.
Further work to achieve this goal is currently underway.
´
8. Hernandez, J. N.; Ramirez, M. A.; Martın, V. S. J. Org.
Chem. 2003, 68, 743–746.
9. Tice, C. M.; Ganem, B. J. Org. Chem. 1983, 48, 5043–
5048.
10. Gray, D.; Concellon, C.; Gallagher, T. J. Org. Chem.
2004, 69, 4849–4851.
11. For example, see: (a) Goldstein, D. M.; Wipf, P. Tetra-
hedron Lett. 1996, 37, 739–742; (b) Chandrasekhar, S.;
Shyamsunder, T.; Chandrashekar, G.; Narsihmulu, C.
Synlett 2004, 522–524; (c) Fuerstner, A.; Feyen, F.; Prinz,
H.; Waldmann, H. Tetrahedron 2004, 60, 9543–9558.
12. (a) Anet, E. F. L. J.; Lythgoe, B.; Silk, M. H.; Trippett, S.
J. Chem. Soc. 1953, 309–319; (b) Pandey, R. C.; German,
V. F.; Nishikawa, Y.; Rinehart, K. L., Jr. J. Am. Chem.
Soc. 1971, 93, 3738–3747.
23
22
13. Optical rotation for 1: ½aꢁD +10.0 (c 0.2, H2O); lit.2c ½aꢁD
+10.3 (c 1.3, H2O). Spectroscopic data were entirely
consistent with those published for (S)-gizzerosine.2c,4,5