Solution forms of bouvardin and relatives from NMR studies. 6-O-methylbouvardin

Robert B. Bates, Jack R Cole, Joseph J. Hoffmann, George R. Kriek, Gary S. Linz, Sterling J. Torrance

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

1H and 13C NMR studies indicate that the predominant stereoisomer and conformer in solution for the potent natural antitumor agents deoxybouvardin (1), bouvardin (2), and the newly isolated and equally active 6-O-methylbouvardin (3) is that found in the solid state by X-ray diffraction. Unusual features in the spectra, all in the vicinity of the 14-membered ring, include an aromatic proton absorbing unusually far upfield at δ 4.35, a vicinal H-C-O-H coupling constant of 10.2 Hz, aryl carbons ortho to an ether oxygen absorbing at δ 124.2-125.9, and a geminal coupling constant of -20 Hz between the methylene protons in a tyrosine residue. A minor stereoisomer (∼15%) separated by a 20.6 kcal/mol barrier is observed for 1-3; variable-temperature 1H NMR studies on model N-methyl peptides indicate this stereoisomer to differ in rotation about the Tyr-5 and/or Tyr-3 amide bond. Since the antitumor activities of six compounds differing in substitution on Tyr-5 and Tyr-6 do not vary appreciably while a change in Tyr-3 results in loss of activity, the rigid 14-membered ring portion of the molecule is not the active part but serves to get the rest of the molecule into the active conformation.

Original languageEnglish (US)
Pages (from-to)1343-1347
Number of pages5
JournalJournal of the American Chemical Society
Volume105
Issue number5
StatePublished - 1983

Fingerprint

bouvardin
Stereoisomerism
Protons
Nuclear magnetic resonance
Molecules
Amides
Peptides
Conformations
Ethers
Substitution reactions
X-Ray Diffraction
X ray diffraction
Antineoplastic Agents
Ether
Carbon
Oxygen
Tyrosine
Temperature
6-O-methylbouvardin

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Bates, R. B., Cole, J. R., Hoffmann, J. J., Kriek, G. R., Linz, G. S., & Torrance, S. J. (1983). Solution forms of bouvardin and relatives from NMR studies. 6-O-methylbouvardin. Journal of the American Chemical Society, 105(5), 1343-1347.

Solution forms of bouvardin and relatives from NMR studies. 6-O-methylbouvardin. / Bates, Robert B.; Cole, Jack R; Hoffmann, Joseph J.; Kriek, George R.; Linz, Gary S.; Torrance, Sterling J.

In: Journal of the American Chemical Society, Vol. 105, No. 5, 1983, p. 1343-1347.

Research output: Contribution to journalArticle

Bates, RB, Cole, JR, Hoffmann, JJ, Kriek, GR, Linz, GS & Torrance, SJ 1983, 'Solution forms of bouvardin and relatives from NMR studies. 6-O-methylbouvardin', Journal of the American Chemical Society, vol. 105, no. 5, pp. 1343-1347.
Bates, Robert B. ; Cole, Jack R ; Hoffmann, Joseph J. ; Kriek, George R. ; Linz, Gary S. ; Torrance, Sterling J. / Solution forms of bouvardin and relatives from NMR studies. 6-O-methylbouvardin. In: Journal of the American Chemical Society. 1983 ; Vol. 105, No. 5. pp. 1343-1347.
@article{47fe44752091440399bf565b623c7224,
title = "Solution forms of bouvardin and relatives from NMR studies. 6-O-methylbouvardin",
abstract = "1H and 13C NMR studies indicate that the predominant stereoisomer and conformer in solution for the potent natural antitumor agents deoxybouvardin (1), bouvardin (2), and the newly isolated and equally active 6-O-methylbouvardin (3) is that found in the solid state by X-ray diffraction. Unusual features in the spectra, all in the vicinity of the 14-membered ring, include an aromatic proton absorbing unusually far upfield at δ 4.35, a vicinal H-C-O-H coupling constant of 10.2 Hz, aryl carbons ortho to an ether oxygen absorbing at δ 124.2-125.9, and a geminal coupling constant of -20 Hz between the methylene protons in a tyrosine residue. A minor stereoisomer (∼15{\%}) separated by a 20.6 kcal/mol barrier is observed for 1-3; variable-temperature 1H NMR studies on model N-methyl peptides indicate this stereoisomer to differ in rotation about the Tyr-5 and/or Tyr-3 amide bond. Since the antitumor activities of six compounds differing in substitution on Tyr-5 and Tyr-6 do not vary appreciably while a change in Tyr-3 results in loss of activity, the rigid 14-membered ring portion of the molecule is not the active part but serves to get the rest of the molecule into the active conformation.",
author = "Bates, {Robert B.} and Cole, {Jack R} and Hoffmann, {Joseph J.} and Kriek, {George R.} and Linz, {Gary S.} and Torrance, {Sterling J.}",
year = "1983",
language = "English (US)",
volume = "105",
pages = "1343--1347",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "5",

}

TY - JOUR

T1 - Solution forms of bouvardin and relatives from NMR studies. 6-O-methylbouvardin

AU - Bates, Robert B.

AU - Cole, Jack R

AU - Hoffmann, Joseph J.

AU - Kriek, George R.

AU - Linz, Gary S.

AU - Torrance, Sterling J.

PY - 1983

Y1 - 1983

N2 - 1H and 13C NMR studies indicate that the predominant stereoisomer and conformer in solution for the potent natural antitumor agents deoxybouvardin (1), bouvardin (2), and the newly isolated and equally active 6-O-methylbouvardin (3) is that found in the solid state by X-ray diffraction. Unusual features in the spectra, all in the vicinity of the 14-membered ring, include an aromatic proton absorbing unusually far upfield at δ 4.35, a vicinal H-C-O-H coupling constant of 10.2 Hz, aryl carbons ortho to an ether oxygen absorbing at δ 124.2-125.9, and a geminal coupling constant of -20 Hz between the methylene protons in a tyrosine residue. A minor stereoisomer (∼15%) separated by a 20.6 kcal/mol barrier is observed for 1-3; variable-temperature 1H NMR studies on model N-methyl peptides indicate this stereoisomer to differ in rotation about the Tyr-5 and/or Tyr-3 amide bond. Since the antitumor activities of six compounds differing in substitution on Tyr-5 and Tyr-6 do not vary appreciably while a change in Tyr-3 results in loss of activity, the rigid 14-membered ring portion of the molecule is not the active part but serves to get the rest of the molecule into the active conformation.

AB - 1H and 13C NMR studies indicate that the predominant stereoisomer and conformer in solution for the potent natural antitumor agents deoxybouvardin (1), bouvardin (2), and the newly isolated and equally active 6-O-methylbouvardin (3) is that found in the solid state by X-ray diffraction. Unusual features in the spectra, all in the vicinity of the 14-membered ring, include an aromatic proton absorbing unusually far upfield at δ 4.35, a vicinal H-C-O-H coupling constant of 10.2 Hz, aryl carbons ortho to an ether oxygen absorbing at δ 124.2-125.9, and a geminal coupling constant of -20 Hz between the methylene protons in a tyrosine residue. A minor stereoisomer (∼15%) separated by a 20.6 kcal/mol barrier is observed for 1-3; variable-temperature 1H NMR studies on model N-methyl peptides indicate this stereoisomer to differ in rotation about the Tyr-5 and/or Tyr-3 amide bond. Since the antitumor activities of six compounds differing in substitution on Tyr-5 and Tyr-6 do not vary appreciably while a change in Tyr-3 results in loss of activity, the rigid 14-membered ring portion of the molecule is not the active part but serves to get the rest of the molecule into the active conformation.

UR - http://www.scopus.com/inward/record.url?scp=0020620065&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0020620065&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:0020620065

VL - 105

SP - 1343

EP - 1347

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 5

ER -