Total syntheses of bengamides B and E.
Total syntheses of the cytotoxic marine natural products bengamides B and E are described. Both bengamides are prepared via amide coupling of a protected polyhydroxylated lactone intermediate 9 with a suitably substituted aminocaprolactam intermediate. Lactone 9 is prepared in five steps from commercially available alpha-D-glucoheptonic gamma-lactone. The key reactions are a selective deprotection of a 1,2-acetonide in the presence of a 1,3-acetonide and an (E)-selective olefination of an unstable aldehyde using a gem-dichromium reagent. The bengamide B lactam intermediate 10 is prepared in seven steps from commercially available (5R)-5-hydroxy-L-lysine (12). The desired S-configuration at the gamma-OH lactam position is established using the Mitsunobu reaction.
Kinder
F R
FR
Oncology Department, Novartis Pharmaceuticals Corporation, 556 Morris Avenue, Summit, New Jersey 07901, USA. frederick.kinder@pharma.novartis.com
Wattanasin
S
S
Versace
R W
RW
Bair
K W
KW
Bontempo
J
J
Green
M A
MA
Lu
Y J
YJ
Marepalli
H R
HR
Phillips
P E
PE
Roche
D
D
Tran
L D
LD
Wang
R
R
Waykole
L
L
Xu
D D
DD
Zabludoff
S
S
D000818:Animals; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry
D001381:Azepines; C427480:bengamide B; C427481:bengamide E