Total Synthesis of Kendomycin- An Odyssey in C-Aryl ... · Total Synthesis of Kendomycin-An Odyssey...
Transcript of Total Synthesis of Kendomycin- An Odyssey in C-Aryl ... · Total Synthesis of Kendomycin-An Odyssey...
Total Synthesis of Kendomycin-An Odyssey in C-Aryl Glycoside
SynthesisLiterature References
1] Yuan Yu.; Men Hong Bin.; Lee, C. J.Am.Chem.Soc.ASAP
2] Martin, H.J.; Drescher, M.; Kählig, H.; Schneider,S.; Mulzer, J. Angew.Chem.Int.Ed. 2001, 40, 31863] Marques, M.B.M.; Pichlmair, S.; Martin, J.H.;
Mulzer, J. Synthesis 2002, 18, 27664] Pichlmair, S.; Marques, M.; Green, M.P.; Martin,
H.J.; Mulzer, J. Org.Lett. 2003, 5, 46575] Mulzer, J.; Pichlmair, S.; Green, M.P.; Marques,
M.B.M.; Martin, H.J. Proc.Nat.Acad.Sci.2004, 119806] Sengoku, T.; Arimoto, H.; Uemura, D. Chem.Comm.
2004, 1220Literature TalkOct. 28 2004 Vijay Gopalsamuthiram
Glycopeptide Antibiotics as Last Line of DefenseAgainst Bacterial Infection
And other Semisynthetic Analogs
Kendomycin [(-)TAN 2162] - A C-Aryl Glycoside
Polyketide isolated from different Streptomyces sp. by Funahashi in 1996 Potent endothelin receptor antagonist and antiosteoporotic compound Re-isolated by Zeeck in 2000 (70 mg/l) from Streptomyces violaceoruber and was shown to degrade natural rubber Remarkable Antibacterial activity against Gram positive and Gram negative bacteriaparticularly against Staphylococcus aureus strains Highly cytotoxic against tumor cell linesBiosynthesis has been proposed recently by Zeeck
Interesting Facts
Atropisomerism about sp2-Sp3 C-C Bond in 23
Broad signals in HNMR forH’s at C-5, C-6 and C1a were observed due to dynamic effectNo signals in 13C were observedfor C5, C6 and C1a At Lower temperature Benzylic H’s showed a doublet J1,2 = 10.7 Hz
Rotamer Identification by NOE
Rotamer ratio at -40 °C = 93:7
9-epi 23 shows sharp signals over entire temp range due to axialdisposition of C-9 substituent that leads to twist conformation ofTHP ring and thereby greater degree of rotational freedom of arylresidue
Ring Closing Metathesis of Precursor 2a
Grubbs 2nd generation catalysts (or)
Schrock's Catalysts
Failed