3
Brussee, J.; van der Marel, G. A.; Overkleeft, H. S. Org.
Lett.2010, 12, 3957-3959. c) Niwa, T.; Inouye, S.; Tsuruoka, T.;
hydrogenation conditions using hydrogen (60 Psi) and palladium
over carbon as the catalyst in methanol to provide amide 10 in 80
Niida, T.; Koaze, Y. Agric. Biol.Chem. 1970, 34, 966–967. d) Iida,
H.; Yamazaki, N.; Kibayashi. C. J. Org. Chem. 1987, 52, 3337-
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Ojima, I; Vidal, E. S. J. Org. Chem. 1998, 63, 7999-8003.
Scott, J. D.; Williams, R. M. J. Am. Chem. Soc. 2002, 124, 2951-
%
yield. In order to check the enantiomeric purity, the amide 10
was subjected to reduction using lithium aluminum hydride in
anhydrous THF, where interestingly the ester and amide
reduction as well as TBS deprotection was observed in a single
step. The LAH mediated reduction of 10 as well as N-Boc
protection provided N-Boc amine 19. The chiral HPLC analysis
8
9
.
.
2
956.
1
0 . a) Chavan, S. P.; Harale, K. R.; Dumare, N. B.; Kalkote, U. R.
Tetrahedron: Asymmetry 2011, 22, 587-590. b) Chavan, S. P.;
Dumare, N. B.; Harale, K. R.; Kalkote, U. R. Tetrahedron Lett.
1
4
of the 19 revealed that its chiral purity to be >99 %ee. The
amide 10 was subjected to selective reduction of amide group in
presence of ester group to provide amino-ester 18 in 78 % yield.
Finally, the acid hydrolysis of the amino-ester 18 using 6N HCl
2
011, 52, 404-406.
1
1 . For some recent syntheses of 3-hydroxypipecolic acids, see:
a) Chattopadhyay, S. K.; Roy, S. P.; Saha, T. Synthesis 2011,
2
7
664-2670. b) Lemire. A.; Charette. A. B. J. Org. Chem. 2010,
5, 2077–2080. c) Chiou, W.H.; Lin, G. H.; Liang.; C. W. J.
Org. Chem. 2010, 75, 1748–1751. d) Chung, H. S.; Shin, W. K.;
Choi, S. Y.; Chung, Y. K.; Lee, E. Tetrahedron Lett. 2010, 51,
7
07-708. e) Yoshimura, Y.; Ohara, C.; Miyagawa, T.; Takahata,
H. Heterocycles 2009, 77, 635-644. f) Wang, B.; Run-Hua L. Eur.
J. Org. Chem. 2009, 2845–2851. g) Kumar, P. S.; Baskaran, S.
Tetrahedron Lett. 2009, 50, 3489-3492. h) Cochi, A.; Burger, B.;
Navarro, C.; Pardo, D. G.; Cossy, J.; Zhao, Y.; Cohen, T. Synlett
2
009, 2157-2161. i) Yoshimura, Y.; Ohara, C.; Imahori, T.; Saito,
Scheme 3. Global one pot ester, lactam reduction and TBS group
Y.; Kato, A.; Miyauchi, S.; Adachi, I.; Takahata, H. Bioorg. Med.
Chem. 2008, 16, 8273-8286. j) Pham, V.-T.; Joo, J.-E.; Tian, Y.-
S.; Chung, Y.-S.; Lee, K.-Y.; Oh, C.-Y.; Ham, W.-H.
deprotection followed by Boc protection.
Tetrahedron: Asymmetry 2008, 19, 318-321. k) Ohara, C.;
Takahashi, R.; Miyagawa, T.; Yoshimura, Y.; Kato, A.; Adachi,
I.; Takahata, H. Bioorg. Med. Chem. Lett. 2008, 18, 1810-1813. l)
Liu, L.-X.; Peng, Q.-L.; Huang, P.-Q. Tetrahedron: Asymmetry
under heating conditions resulted in formation of the target
molecule (2S,3S)-3-hydroxypipecolic acid 1 in 91% yield.
In conclusion, a short total synthesis of 3-hydroxypipecolic
acid 1 has been achieved starting from cheap and abundant
starting material L-(+)-tartaric acid in 11 steps in 12.3% overall
2
008, 19, 1200-1203. m) Alegret, C.; Ginesta, X.; A. Riera. Eur. J.
Org. Chem. 2008, 1789–1796.
12 . Becker, M. H.; Chua, P.; Downham, R.; Douglas, C. J.; Garg, N.
K.; Hiebert, S.; Jaroch, S.; Matsuoka, R. T.; Middleton, J. A.; Ng,
F. W.; Overman, L. E. J. Am. Chem. Soc. 2007, 129, 11987-
1
5
yield. The main steps used are the selective ester group
reduction, reductive lactamization and selective lactam reduction
to amine. The intermediate 11 could be further explored for the
synthesis of other imino sugars.
1
2002.
1
1
3 . Kim, K. I.; Lill-Elghanian, D. A.; Hollingsworth, R. I. Bioorg.
Med. Chem. Lett. 1994, 4, 1691-1696.
4 . HPLC detail for racemic dihydroxy compound (19) HPLC
chiracel OJ-H column (250 x 4.6 mm). Isopropanol/pet ether =
Acknowledgments
5
=
:95 flow rate 0.5 ml/min, λ = 210 nm) retention time (min): Rt1
12.80; Rt2 = 14.29 (1:1). Enantiomerically pure dihydroxy
K.R.H. and KPP thank CSIR, New Delhi, India for fellowship,
Dr U. R. Kalkote and Dr. H. B. Borate for helpful discussions
and Mrs. S.S. Kunte for HPLC analysis.
compound (19) HPLC chiracel OJ-H column (250 x 4.6 mm)
isopropanol/pet ether = 5:95 flow rate 0.5 ml/min, λ = 210 nm)
retention time (min): 14.20 (exclusive).
1
5. (2S, 3S)-3-hydroxypipecolic acid (1): mp : 238–243 ºC ( lit. 230-
2
D
5
2
38 °C; [α]
: +13.8 º (c 1.0, HCl 10% aq.) lit. +13º (c 0.49,
6
c
HCl 10% aq.) IR (CHCl
3
) υmax: 3287, 2920, 1625, 1405 cm–1.
O) : δ 4.17- 4.13 (m, 1H), 3.83 (d, J = 7.8
Hz, 1H), 3.40-3.36 (m, 1H), 3.07-3.12 (m, 1H), 2.22 (s, 1H), 2.02-
References and notes
1
;
H NMR (400 MHz, D
2
13
2
.08 (m, 2H), 1.80-1.64 (m, 2H). C-NMR (100 MHz, D2O): δ
1
.
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1
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