Total syntheses of (+/-)-anchinopeptolide D and (+/-)-cycloanchinopeptolide D.
The first synthesis of (+/-)-anchinopeptolide D (4) has been accomplished in seven steps in 10% overall yield from octopamine hydrochloride (17), N-(Boc)glycine (16), and 5-amino-2-hydroxypentanoic acid (22). The key step is the aldol dimerization and hemiaminal formation of alpha-keto amide 26, which gives primarily protected anchinopeptolide D 27 under kinetically controlled conditions. Cycloanchinopeptolide D (31) has been prepared by the unprecedented head-to-head photodimerization of the two hydroxystyrylamides of 4 using the hydrophobic effect in water to force the two side chains into close proximity so that [2 + 2] cycloaddition is faster than trans to cis double bond isomerization. Coupling of amine 21 with pyroglutamic acid affords the naturally occurring tripeptide 35, which had been assigned glutamic acid structure 34.
Snider
B B
BB
Department of Chemistry, Brandeis University, Waltham, Massachusetts 02454-9110, USA.
Song
F
F
Foxman
B M
BM
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D005998:Glycine / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D010777:Photochemistry; D013055:Spectrophotometry, Infrared
D000470:Alkaloids; C415028:anchinopeptolide D; D005998:Glycine