Ecteinascidins 729, 743, 745, 759A, 759B, and 770: Potent Antitumor Agents from the Caribbean Tunicate Ecteinascidia turbinata

Journal of Organic Chemistry

Volumn 55, Issue 15, 1990, Pages 4512-4515

  Rinehart, Kenneth L ^a   Holt, Tom G ^a   Fregeau, Nancy L ^a   Stroh, Justin G ^a   Keifer, Paul A ^a   Sun, Furong ^a   Li, Li H ^a   Martin, David G ^a  

^a UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ECTEINASCIDIN 729; ECTEINASCIDIN 745; ECTEINASCIDIN 759A; ECTEINASCIDIN 759B; ECTEINASCIDIN 770; TRABECTEDIN; UNCLASSIFIED DRUG;

ARTICLE; DRUG ISOLATION; DRUG STRUCTURE; INVERTEBRATE; MASS SPECTROMETRY; NONHUMAN;

EID: 0025070774     PISSN: 00223263     EISSN: 15206904     Source Type: Journal    
DOI: 10.1021/jo00302a007     Document Type: Article

References (45)

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3. Rinehart, K. L. Presented at the 30th Ann. Mtg. Am. Soc. Pharmacognosy, San Juan, Puerto Rico, Aug. 6-10, 1989; paper S:9; cf.
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5. Rinehart, K. L. Presented at the 2nd Intl. Symp. Mass Spectrom. Health Life Sci., San Francisco, CA, Aug. 27–31, 1989. Cf.
6. Rinehart, K. L.; Holt, T. G.; Fregeau, N. L.; Staley, A. L.; Thompson, A. G.; Harada, K.-I.; Curtis, J. M.; Rong, L.-S.; Sun, F.; Shield, L. S.; Gade, G.; Grimmelikhuijzen, C. J. P.; Doughty, C. C.; Grimshaw, C. E. In Biological Mass Spectrometry; Burlingame, A. L., McCloskey, J. A., Eds.; Elsevier: Amsterdam, 1990; pp 233–258.
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30. All NMR values are for CDC13 solutions.
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32. The aromatic hydrogens of unit C were initially assigned in two separate aromatic rings, l.a.c.f each bearing a single aromatic hydrogen, since neither the protons nor their attached carbons are correlated in any way with one another.
33. The detailed argument goes as follows. The δ 42.2 methylene carbon is not attached to nitrogen because its protons are too far upfield (cf. C-3’), not attached to the δ 42.1 or 82.1 methines due to lack of splitting, not attached to the ester carbonyl due to lack of long-range correlation of its protons with δ 172.5, and must, therefore, be attached to the quaternary carbon (6 64.7) and to the sulfide. This quaternary carbon is sufficiently deshielded that it must be attached to nitrogen. The sulfide is not attached to the nitrogen or the quaternary carbon due to instability (N-S bond, episulfide), not attached to the carbonyl (a standard ester at δ 172.5) or the 82,1 ppm methine since a sulfur is not sufficiently deshielding, and must, therefore, be attached to the δ 42.1 methine. The carbonyl carbon is not attached to nitrogen since it is a standard ester (δ 172.5), not a urethane; not attached to the too highly deshielded methine at 82.1 ppm; and must, therefore, be attached to the quaternary carbon at δ 64.7. (b) These attachments are in part confirmed by total correlation spectroscopy (TOCSY) 18 experiments in which both protons of the isolated methylene show correlations to the methine protons along the top of units A and B (4.50, 4.18 and 3.59 ppm), and by the loss of CH 2=SH in the FABMS/MS spectra.
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35. The structure which would result from this junction has been proposed for Et 743 (and a similar structure for Et 729) by Wright (adjacent communication). The correct placement of substituents on rings B and C was first proposed by the Harbor Branch group (O. J. McConnell, private communication).
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42. The designations Et 729, 743, 745, 759A, 759B, and 770 were originally employed1a,b as indicative of the compounds’ molecular weights and are retained to avoid confusion, in spite of their real (hydrated) molecular weights—Et 729 (747), Et 743 (761), Et 759A, B (777).
43. He, H.-y.; Faulkner, D. J. J. Org. Chem. 1989, 54, 5822–5824.
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