A concise, stereocontrolled synthesis of (-)-saframycin A by the directed condensation of α-amino aldehyde precursors [1]

Journal of the American Chemical Society

Volumn 121, Issue 46, 1999, Pages 10828-10829

  Myers, Andrew G ^a   Kung, Daniel W ^a  

^a HARVARD UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALDEHYDE DERIVATIVE; AMINE; SAFRAMYCIN A;

AMINATION; CYCLIZATION; DRUG STRUCTURE; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; LETTER; NONHUMAN; STEREOCHEMISTRY;

EID: 0033601117     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja993079k     Document Type: Letter

References (13)

1. Reviews: (a) Arai, T.; Kubo, A. In The Alkaloids; Brossi, A., Ed.; Academic Press: New York, 1983; Vol. 21, Chapter 3. (b) Remers, W. A. In The Chemistry of Antitumor Antibiotics; Wiley-Interscience: New York, 1988; Vol. 2, Chapter 3.
2. Reviews: (a) Arai, T.; Kubo, A. In The Alkaloids; Brossi, A., Ed.; Academic Press: New York, 1983; Vol. 21, Chapter 3. (b) Remers, W. A. In The Chemistry of Antitumor Antibiotics; Wiley-Interscience: New York, 1988; Vol. 2, Chapter 3.
3. Previous syntheses of the saframycins: (±)-Saframycin B: (a) Fukuyama, T.; Sachleben, R. A. J. Am. Chem. Soc. 1982, 104, 4957-4958. (b) Kubo, A.; Saito, N.; Yamato, H.; Masubuchi, K.; Nakamura, M. J. Org. Chem. 1988, 53, 4295-4310. (±)-Saframycin A: (c) Fukuyama, T.; Yang, L.; Ajeck, K. L.; Sachleben. R. A. J. Am. Chem. Soc. 1990, 112, 3712-3713. (-)-Saframycin A: (d) Martinez, E. J.; Corey, E. J. Org. Lett. 1999, 1, 75-77. See also: (e) Zhou, B.; Edmondson, S.; Danishefsky, S. J. Tetrahedron Lett. Submitted for publication. (f) Zhou, B.; Danishefsky, S. J. Tetrahedron Lett. Submitted for publication.
4. Previous syntheses of the saframycins: (±)-Saframycin B: (a) Fukuyama, T.; Sachleben, R. A. J. Am. Chem. Soc. 1982, 104, 4957-4958. (b) Kubo, A.; Saito, N.; Yamato, H.; Masubuchi, K.; Nakamura, M. J. Org. Chem. 1988, 53, 4295-4310. (±)-Saframycin A: (c) Fukuyama, T.; Yang, L.; Ajeck, K. L.; Sachleben. R. A. J. Am. Chem. Soc. 1990, 112, 3712-3713. (-)-Saframycin A: (d) Martinez, E. J.; Corey, E. J. Org. Lett. 1999, 1, 75-77. See also: (e) Zhou, B.; Edmondson, S.; Danishefsky, S. J. Tetrahedron Lett. Submitted for publication. (f) Zhou, B.; Danishefsky, S. J. Tetrahedron Lett. Submitted for publication.
5. Previous syntheses of the saframycins: (±)-Saframycin B: (a) Fukuyama, T.; Sachleben, R. A. J. Am. Chem. Soc. 1982, 104, 4957-4958. (b) Kubo, A.; Saito, N.; Yamato, H.; Masubuchi, K.; Nakamura, M. J. Org. Chem. 1988, 53, 4295-4310. (±)-Saframycin A: (c) Fukuyama, T.; Yang, L.; Ajeck, K. L.; Sachleben. R. A. J. Am. Chem. Soc. 1990, 112, 3712-3713. (-)-Saframycin A: (d) Martinez, E. J.; Corey, E. J. Org. Lett. 1999, 1, 75-77. See also: (e) Zhou, B.; Edmondson, S.; Danishefsky, S. J. Tetrahedron Lett. Submitted for publication. (f) Zhou, B.; Danishefsky, S. J. Tetrahedron Lett. Submitted for publication.
6. Previous syntheses of the saframycins: (±)-Saframycin B: (a) Fukuyama, T.; Sachleben, R. A. J. Am. Chem. Soc. 1982, 104, 4957-4958. (b) Kubo, A.; Saito, N.; Yamato, H.; Masubuchi, K.; Nakamura, M. J. Org. Chem. 1988, 53, 4295-4310. (±)-Saframycin A: (c) Fukuyama, T.; Yang, L.; Ajeck, K. L.; Sachleben. R. A. J. Am. Chem. Soc. 1990, 112, 3712-3713. (-)-Saframycin A: (d) Martinez, E. J.; Corey, E. J. Org. Lett. 1999, 1, 75-77. See also: (e) Zhou, B.; Edmondson, S.; Danishefsky, S. J. Tetrahedron Lett. Submitted for publication. (f) Zhou, B.; Danishefsky, S. J. Tetrahedron Lett. Submitted for publication.
7. Previous syntheses of the saframycins: (±)-Saframycin B: (a) Fukuyama, T.; Sachleben, R. A. J. Am. Chem. Soc. 1982, 104, 4957-4958. (b) Kubo, A.; Saito, N.; Yamato, H.; Masubuchi, K.; Nakamura, M. J. Org. Chem. 1988, 53, 4295-4310. (±)-Saframycin A: (c) Fukuyama, T.; Yang, L.; Ajeck, K. L.; Sachleben. R. A. J. Am. Chem. Soc. 1990, 112, 3712-3713. (-)-Saframycin A: (d) Martinez, E. J.; Corey, E. J. Org. Lett. 1999, 1, 75-77. See also: (e) Zhou, B.; Edmondson, S.; Danishefsky, S. J. Tetrahedron Lett. Submitted for publication. (f) Zhou, B.; Danishefsky, S. J. Tetrahedron Lett. Submitted for publication.
8. Previous syntheses of the saframycins: (±)-Saframycin B: (a) Fukuyama, T.; Sachleben, R. A. J. Am. Chem. Soc. 1982, 104, 4957-4958. (b) Kubo, A.; Saito, N.; Yamato, H.; Masubuchi, K.; Nakamura, M. J. Org. Chem. 1988, 53, 4295-4310. (±)-Saframycin A: (c) Fukuyama, T.; Yang, L.; Ajeck, K. L.; Sachleben. R. A. J. Am. Chem. Soc. 1990, 112, 3712-3713. (-)-Saframycin A: (d) Martinez, E. J.; Corey, E. J. Org. Lett. 1999, 1, 75-77. See also: (e) Zhou, B.; Edmondson, S.; Danishefsky, S. J. Tetrahedron Lett. Submitted for publication. (f) Zhou, B.; Danishefsky, S. J. Tetrahedron Lett. Submitted for publication.
9. Myers, A. G.; Kung, D. W.; Zhong, B.; Movassaghi, M.; Kwon, S. J. Am. Chem. Soc. 1999, 121, 8401-8402.
10. Myers, A. G.; Schnider, P.; Kwon, S.; Kung, D. W. J. Org. Chem. 1999, 64, 3322-3327.
11. The sequence of reactions shown in Scheme 2 has been conducted independently with both the (R)- [depicted] and (S)-morpholino nitrile diastereomers. The yields and selectivities in both sequences were nearly identical and in no event was scrambling of the morpholino nitrile stereochemistry observed. We have also successfully executed the sequence using a ∼1:1 mixture of the (R)- and (S)-diastereomers, converging on the intermediate 2, this being the preferred route for large-scale synthesis of 1 and 2.
12. Guibe, F.; Grierson, D. S.; Husson, H.-P. Tetrahedron Lett. 1982, 23, 5055-5058.
13. Two unstable byproducts, tentatively assigned as the regioisomeric o-,p-and p-,o-quinones, were also isolated in a combined yield of ∼15%.