Synthetic Efforts Toward Palau'amine Doug Behenna, Ryan McFadden Eric Ashley, Jenn Stockdill Akihiko Iwashita August 9, 2004 N N N H N O NH 2 H N NH H H OH NH 2 Cl H 2 N N N N H N O NH 2 H N NH H H OH NH 2 Cl H 2 N R 1 R 2 N N H N HN O NH 2 H N NH H H OH NH 2 Cl H 2 N R 2 R 1 R 1 = R 2 = H Palau'amine R 1 = H, R 2 = Br 4-Bromo Palau'amine R 1 = R 2 = Br Dibromo Palau'amine R 1 = R 2 = H Styloguanidine R 1 = H, R 2 = Br 3-Bromo Styloguanidine R 1 = R 2 = Br Dibromo Styloguanidine Isolation of Palau'amine and Congeners Palau'amines • Isolated from marine sponge Stylotella aurantium • Structural determination by 1 HNMR • Cytotoxic against P-388 (0.1 μg/mL), A549 (0.2 μg/mL), HT-29 (2μg/mL) and KB (10 μg/mL) • Antibiotic against Staphylococcus aureus and Bacillus subtillus • Antifungal against Penicillium notatum • Kinnel, R. B. et. al. J. Am. Chem. Soc. 1993, 115, 3376-3377 and J. Org. Chem. 1998, 63, 3281-3886. Styloguanidines • Isolated from marine sponge Stylotella aurantium • Structural determination by 1 HNMR • All three compounds are potent chitinase inhibitors • First reported by Kato, T. et. al. Tetrahedron Lett. 1995, 36, 2133-2136. • Also reported in Kinnel's second paper. 1
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Isolation of Palau'amine and Congeners Synthetic Efforts ......Austin, D. J., et. al., Org. Lett. 2003, 5, 2203-2206. N N H N N H2N O NH2 Cl N HN H2N HO The Pauson-Khand Approach O
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Synthetic Efforts Toward Palau'amineDoug Behenna, Ryan McFadden
Eric Ashley, Jenn StockdillAkihiko Iwashita
August 9, 2004
N
N
NH
N
O
NH2
H
N
NH
H
H
OH
NH2
ClH2N
N
N
NH
N
O
NH2
H
N
NH
H
H
OH
NH2
ClH2N
R1R2
N NH
NHN
O
NH2
H
N
NH
H
H
OH
NH2
ClH2N
R2R1
R1 = R2 = H Palau'amine
R1 = H, R2 = Br 4-Bromo Palau'amine
R1 = R2 = Br Dibromo Palau'amine
R1 = R2 = H Styloguanidine
R1 = H, R2 = Br 3-Bromo Styloguanidine
R1 = R2 = Br Dibromo Styloguanidine
Isolation of Palau'amine and Congeners
Palau'amines
• Isolated from marine sponge Stylotella aurantium
• Structural determination by 1HNMR
• Cytotoxic against P-388 (0.1 µg/mL), A549 (0.2
µg/mL), HT-29 (2µg/mL) and KB (10 µg/mL)
• Antibiotic against Staphylococcus aureus and
Bacillus subtillus
• Antifungal against Penicillium notatum
• Kinnel, R. B. et. al. J. Am. Chem. Soc. 1993, 115,
3376-3377 and J. Org. Chem. 1998, 63, 3281-3886.
Styloguanidines
• Isolated from marine sponge Stylotella aurantium
• Structural determination by 1HNMR
• All three compounds are potent chitinase inhibitors
• First reported by Kato, T. et. al. Tetrahedron Lett.
1995, 36, 2133-2136.
• Also reported in Kinnel's second paper.
1
Biosynthesis of Palau'amine
CO2H
NH2
N
HN
Histidine
N
HN
NH2N
N
NH2H2N H2N
HN
CO2H
Proline
HN
CO2H
HN
CO2HBr
Br
N
N
NH2H2N
HN
CO2H+N
N
NH
H2N
O
HN
Mourabit, A. A.; Potier, P. Eur. J. Org. Chem., 2001, 237-243.
N
HN
NH2H2N
N
N
NH
H2N
O
HN+
NH
O
HN
NH2Cl
OH
N
HN
H2N
N
N
H2N
NH
O
HN
NH2
N
HN
H2N
HN
N
HN
HO
Cl
NH
OHN
NH2Cl
HN
NH2N
HO
N
N
H2N
Biosynthesis of Palau'amine
2
NH
OHN
NH2Cl
HN
NH2N
HO
N
N
H2N
NH2Cl
HN
NH2N
HO
N
OHN
N
NH
H2N
NH2Cl
HN
NH2N
HO
N
OHN
N
NH
HN
N
N
NH
N
O
H2N
H
N
HN
H
H
HO
H2N
ClNH2
Biosynthesis of Palau'amine
[O]
Palau'amine
Overman's Stereocontrolled Synthesisof the Tetracyclic Palau'amine Core