Acid and base catalysed rearrangements of 9,10-dioxotaxanes

Tetrahedron Letters

Volumn 37, Issue 5, 1996, Pages 727-730

  Appendino, Giovanni ^a   Jakupovic, Jasmin ^b   Varese, Marcella ^a   Bombardelli, Ezio ^c  

^a UNIVERSITY OF TURIN   (Italy)

^b TECHNISCHE UNIVERSITÄT BERLIN   (Germany)

^c INDENA S P A   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

TAXANE DERIVATIVE;

ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; NUCLEAR MAGNETIC RESONANCE;

EID: 0030053969     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(95)02254-6     Document Type: Article

References (17)

1. Part XXIV in the series The Chemistry and Occurrence of Taxane Derivatives. For part XXIII, see reference 3 This paper is dedicated to the memory of Pierluigi Gariboldi, with whom we would have loved to share the excitement of natural products research for a much longer time.
2. Appendino, G., Nat. Prod. Rep 1995, 12, 349-360
3. Torregiani, E.; Rafaiani, G.; Barboni, L.; Appendino, G. Tetrahedron Lett. 1995, 7127-7128.
4. Vander Velde, D.G.; Georg, G.I.; Gollapudi, S.R.; Jampani, H.B.; Liang, X.-Z.; Mitscher, L.A.; Ye, Q.-M. J Nat. Prod. 1994, 57, 862-867.
5. Appendino, G.; Fenoglio, I.; Cravotto, G.; Varese, M.; Gariboldi, P.; Gabetta, B. Gazz. Chim. Ital. 1994, 24, 253-257.
6. 13C NMR spectra of 3 and 5 were assigned with the aid of NOE-inspection and the HMBC spectra
7. Chen, S.-H.; Huang, S.; Wei, J.; Farina, V. Tetrahedron 1993, 49, 2805-2828.
8. Gabetta, B.; Peterlongo, F.; Zini, G.; Barboni, L.; Rafaiani, G.; Ranzuglia, P.; Torregiani, E.; Appendino, G.; Cravotto, G. Phytochemistry 1995 (in press)
9. To avoid electrostatic repulsion by the oxygen lone-pairs, nucleophiles approach a carbonyl group at an angle of about 107° (Bürgi, H.B., Dunitz, J.D., Shefter, E. J. Am. Chem. Soc 1973, 95, 5065-5067).
10. Models show that the attack to the C-10 carbonyl is favoured by a negative torsion angle around C-9, C-10, whereas a positive torsion angle C-9, C-10 favours attack to the C-9 carbonyl
11. Miller, R.W., Powell, R.G.; Smith Jr., C.R., Arnold, E.; Clardy, J. J. Org. Chem. 1981, 46, 1469-1474.
12. The bidimensional representation of 5 was done according to the Lythgoe convention, that is, the substituents at the bridgehead carbons (C-1, C-8, C-11, C-12) are considered as cyclooctane ring B substituents (Eyre, D.H.; Harrison, J.W.; Lythgoe, B. J. Chem. Soc. (C) 1967, 452-462). For sake of clarity, an alternative and unambiguous representation is also given in Scheme 3. Note that the stereochemical descriptors of the substituents at C-1, C-8, C-11, and C-12 are inverted. For a discussion of the bidimensional representation of taxoids, see: Appendino, G. in The Chemistry and Pharmacology of Taxol® and its Derivatives, Farina, V. Ed., Elsevier, 1995; pp. 13-18.
13. The bidimensional representation of 5 was done according to the Lythgoe convention, that is, the substituents at the bridgehead carbons (C-1, C-8, C-11, C-12) are considered as cyclooctane ring B substituents (Eyre, D.H.; Harrison, J.W.; Lythgoe, B. J. Chem. Soc. (C) 1967, 452-462). For sake of clarity, an alternative and unambiguous representation is also given in Scheme 3. Note that the stereochemical descriptors of the substituents at C-1, C-8, C-11, and C-12 are inverted. For a discussion of the bidimensional representation of taxoids, see: Appendino, G. in The Chemistry and Pharmacology of Taxol® and its Derivatives, Farina, V. Ed., Elsevier, 1995; pp. 13-18.
14. For the rearrangement of a baccatin III derivative into a stable 2,4,20-orthoester, see: Appendino, G.; Varese, M.; Gariboldi, P.; Gabetta, B. Tetrahedron Lett. 1994, 2217-2220.
15. 3, TMS as reference, resonances of the major anomer): δ 206.2 (s, C-9), 201.8 (s, C-10), 170.2 (s, Ac), 165.7 (s, Bz), 132.6 (d, Bz), 131.8 (s, Bz), 129.6 (d, Bz), 128.3 (d, Bz), 100.5 (d, C-7), 94.5 (s, C-4), 84.7 (d, C-5), 83.8 (s, C-1), 78.1 (d, C-2), 72.7 (d, C-13), 67.6 (t, C-20), 59.1 (d, C-11), 53.2 (d, C-3), 52.8 (s, C-8), 43.7 (s, C-12), 43.6 (s, C-15), 41.1 (t, C-6), 38.3 (t, C-14), 28.8 (q, C-16), 28.0 (q, C-18), 21.1 (q, C-17), 20.8 (q, Ac), 184 (q, C-19).
16. The H-5/H-20a,b NOE correlations are especially relevant They show that the rearrangement takes place with an overall retention of configuration at C-5, implying two Sn2-type displacements (see Scheme 3). The cis-relationship between the 19-methyl and H-20a,b is evidenced in the alternative representation of 5.
17. 6 was ca 1:1. Acetylation of 5 afforded an easily separable mixture of anomeric acetates in a cα 1:1 ratio.