D.-G. Qin, Z.-J. Yao / Tetrahedron Letters 44 (2003) 571–574
573
Aurantimycins: Grafe, U.; Schegel, R.; Ritzau, M.; Ihn,
W.; Dornberger, K.; Stengel, C.; Fleck, W. F.; Paulus, E.
F.; Gutsche, W.; Hartl, A. J. Antibiot. 1995, 48, 111; (f)
GE3: Sakai, Y.; Yoshida, T.; Tsujita, T.; Ochiai, K.;
Agatsuma, T.; Saitoh, Y.; Tanaka, F.; Akiyama, T.;
Akinaga, S.; Mizukami, T. J. Antibiot. 1997, 50, 659.
2. Polyoxypeptins A and B: (a) Umezawa, K.; Nakazawa,
K.; Uemura, T.; Ikeda, Y.; Kondo, S.; Naganawa, H.;
Kinoshita, N.; Hasizume, H.; Hamada, M.; Takeuchi, T.;
Ohba, S. Tetrahedron Lett. 1998, 39, 1389; (b) Umezawa,
K.; Nakazawa, K.; Ikeda, Y.; Naganawa, H.; Kondo, S.
J. Org. Chem. 1999, 64, 3034.
3. (a) Umezawa, K.; Nakazawa, K.; Uchihata, Y.; Otsuka,
M. Adv. Enzyme Regul. 1999, 39, 145; (b) Chen, W. H.;
Horoszewicz, J. S.; Leong, S. S.; Shimano, T.; Penetrante,
R.; Sanders, W. H.; Berjian, R.; Douglass, H. O.; Martin,
E. W.; Chu, T. M. In Vitro 1982, 18, 24.
4. For recent efficient syntheses of (2S,3R)-3-hydroxy-3-
methylproline (3-OH MePro), see: (a) Noguchi, Y.;
Uchiro, H.; Yamada, T.; Kobayashi, S. Tetrahedron Lett.
2001, 42, 5253; (b) Qin, D.-G.; Zha, H.-Y.; Yao, Z.-J. J.
Org. Chem. 2002, 67, 1038; (c) Makino, K.; Kondoh, A.;
Hamada, Y. Tetrahedron Lett. 2002, 43, 4695.
5. For an efficient synthesis of (3R)-piperazic acid, see:
Hale, K. J.; Cai, J.; Delisser, V.; Manaviazar, S.; Peak, S.
A.; Bhatia, G. S.; Collins, T. C.; Jogiya, N. Tetrahedron
1996, 52, 1047.
6. For two recent syntheses of (3R,5R)-5-hydroxypiperazic
acid, see: (a) Kamenecka, T. M.; Danishefsky, S. J.
Angew. Chem., Int. Engl. Ed. 1998, 37, 2995; (b) Hale, K.
J.; Jogiya, N.; Manaviazar, S. Tetrahedron Lett. 1998, 39,
7163.
7. Total synthesis of L-156,602: (a) Durette, P. L.; Baker, P.
L.; Boger, J.; Bondy, S. S.; Hammond, M. L.; Lanza, T.
J.; Pessolano, A. A.; Caldwell, C. G. Tetrahedron Lett.
1990, 55, 2355; (b) Caldwell, C. G.; Rupprecht, K. M.;
Bondy, S. S.; Davis, A. A. J. Org. Chem. 1990, 55, 2355.
8. Total synthesis of A83586C: (a) Hale, K. J.; Cai, J. Chem.
Commun. 1997, 2319; (b) Hale, K. J.; Cai, J.; Delisser, V.
M. Tetrahedron Lett. 1996, 37, 9345; (c) Hale, K. J.;
Bhatia, G. S.; Peak, S. A.; Manaviazar, S. Tetrahedron
Lett. 1993, 34, 5343.
Scheme 3.
(Fig. 1, R=Me instead of Et). Fortunately, the methyl
acetal 3 was accidentally transformed into the semi-ace-
tal 12, which was also reported10a recently, after 7 days
standing in a NMR tube, in 70% yield (Scheme 3). The
1H and 13C NMR spectra of the purified diol 1216
coincide with those reported by Kobayashi et al.,10a
while the rotation ([h]2D5=+76.2 (c 0.96, CHCl3)) is
higher than that reported (lit.10a [h]D25=+55 (c 0.36,
CHCl3)). Based on this evidence, it is believed our
samples 3 and 12 are correct albeit with higher enan-
tiomeric purities, and there are probably some unsolved
structural questions associated with compound
3
obtained by Kurosu et al.10b In order to confirm the
orientation of the acetal OCH3, a NOESY spectrum of
3 was measured and clearly showed a strong NOE
between the methyl group and Ha (Scheme 3). Thus,
our sample 3 has the unambiguous stereochemical
configuration as shown in Scheme 3.
In summary, an enantioselective synthesis of the 15-car-
bon tetrahydropyranyl side chain of polyoxypeptins is
reported in 15.5% overall yield. It provides an attractive
effective synthesis of this lactone and also provides a
short route potentially amenable to preparation of the
related compounds such as antibiotic L-156,602. Fur-
ther studies toward the total synthesis of poly-
oxypeptins are now in progress.
Acknowledgements
9. Synthetic studies on GE3: (a) Hale, K. J.; Lazarides, L.
Org. Lett. 2002, 4, 1903; (b) Makino, K.; Henmi, Y.;
Hamada, Y. Synlett 2002, 613.
10. For other synthetic studies on the acyl side chain of the
polyoxypeptins, see: (a) Noguchi, Y.; Yamada, T.;
Uchiro, H.; Kobayashi, S. Tetrahedron Lett. 2000, 41,
7499; (b) Lorca, M.; Kurosu, M. Tetrahedron Lett. 2001,
42, 2431; (c) Makino, K.; Kondoh, A.; Hamada, Y.
Tetrahedron Lett. 2002, 43, 4695.
The Major State Basic Research and Development
Program of China (Grant No. G2000077500), NSFC
(No. 20172061), the Chinese Academy of Sciences, and
the Shanghai Municipal Commission of Science and
Technology are thanked for the financial support. Dr.
Hong-Wang Zhang is thanked for providing the allylic
alcohol 8.
11. Hale, K. J.; Cai, J.; Manaviazar, S.; Peak, S. A. Tetra-
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1
3526, 2960, 2878, 1739, 1463, 1380, 1151, 1055. H NMR
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