Abstract
Aaptamine (1) was used as starting material for synthetic transformation to isoaaptamine (2), 9-demethylaaptamine (5), and 4-methylaaptamine (6). A general method for the selective O-demethylation of such 1H-benzo [de] [1,6]-naphthyridine (1) marine sponge constituents at position C-9 has been developed. Selective O-demethylation of aaptamine (1) and 1-methylaaptamine (11) with 48% hydrobromic acid led to 9-demethylaaptamine (5) and isoaaptamine (2), respectively. A selection of other aaptamine derivatives were synthesized, and their structures were unambiguously determined by X-ray methods. In addition, their cancer cell growth inhibitory properties were evaluated against the murine P388 lymphocytic cell line and a minipanel of human cancer cell lines. Evaluation as inhibitors of the PKC signal transduction pathway and against a selection of microorganisms was also undertaken. Aaptamine derivatives 3 and 5 had broad-spectrum antimicrobial activities.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2251-2256 |
| Number of pages | 6 |
| Journal | Journal of Organic Chemistry |
| Volume | 69 |
| Issue number | 7 |
| DOIs | |
| State | Published - Apr 2 2004 |
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ASJC Scopus subject areas
- Organic Chemistry
Cite this
Antineoplastic Agents 491.1 Synthetic Conversion of Aaptamine to Isoaaptamine, 9-Demethylaaptamine, and 4-Methylaaptamine. / Pettit, George; Hoffmann, Holger; Herald, Delbert L.; McNulty, James; Murphy, Alison; Higgs, Kerianne C.; Hamel, Ernest; Lewin, Nancy E.; Pearce, Larry V.; Blumberg, Peter M.; Pettit, Robin; Knight, John C.
In: Journal of Organic Chemistry, Vol. 69, No. 7, 02.04.2004, p. 2251-2256.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Antineoplastic Agents 491.1 Synthetic Conversion of Aaptamine to Isoaaptamine, 9-Demethylaaptamine, and 4-Methylaaptamine
AU - Pettit, George
AU - Hoffmann, Holger
AU - Herald, Delbert L.
AU - McNulty, James
AU - Murphy, Alison
AU - Higgs, Kerianne C.
AU - Hamel, Ernest
AU - Lewin, Nancy E.
AU - Pearce, Larry V.
AU - Blumberg, Peter M.
AU - Pettit, Robin
AU - Knight, John C.
PY - 2004/4/2
Y1 - 2004/4/2
N2 - Aaptamine (1) was used as starting material for synthetic transformation to isoaaptamine (2), 9-demethylaaptamine (5), and 4-methylaaptamine (6). A general method for the selective O-demethylation of such 1H-benzo [de] [1,6]-naphthyridine (1) marine sponge constituents at position C-9 has been developed. Selective O-demethylation of aaptamine (1) and 1-methylaaptamine (11) with 48% hydrobromic acid led to 9-demethylaaptamine (5) and isoaaptamine (2), respectively. A selection of other aaptamine derivatives were synthesized, and their structures were unambiguously determined by X-ray methods. In addition, their cancer cell growth inhibitory properties were evaluated against the murine P388 lymphocytic cell line and a minipanel of human cancer cell lines. Evaluation as inhibitors of the PKC signal transduction pathway and against a selection of microorganisms was also undertaken. Aaptamine derivatives 3 and 5 had broad-spectrum antimicrobial activities.
AB - Aaptamine (1) was used as starting material for synthetic transformation to isoaaptamine (2), 9-demethylaaptamine (5), and 4-methylaaptamine (6). A general method for the selective O-demethylation of such 1H-benzo [de] [1,6]-naphthyridine (1) marine sponge constituents at position C-9 has been developed. Selective O-demethylation of aaptamine (1) and 1-methylaaptamine (11) with 48% hydrobromic acid led to 9-demethylaaptamine (5) and isoaaptamine (2), respectively. A selection of other aaptamine derivatives were synthesized, and their structures were unambiguously determined by X-ray methods. In addition, their cancer cell growth inhibitory properties were evaluated against the murine P388 lymphocytic cell line and a minipanel of human cancer cell lines. Evaluation as inhibitors of the PKC signal transduction pathway and against a selection of microorganisms was also undertaken. Aaptamine derivatives 3 and 5 had broad-spectrum antimicrobial activities.
UR - http://www.scopus.com/inward/record.url?scp=12144288011&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=12144288011&partnerID=8YFLogxK
U2 - 10.1021/jo0300486
DO - 10.1021/jo0300486
M3 - Article
C2 - 15049616
AN - SCOPUS:12144288011
VL - 69
SP - 2251
EP - 2256
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
SN - 0022-3263
IS - 7
ER -