Total syntheses of (+/-)-anchinopeptolide D and (+/-)-cycloanchinopeptolide D

The first synthesis of (+/-)-anchinopeptolide D (4) has been accomplished i n seven steps in 10% overall yield from octopamine hydrochloride (17), N-(B oc)glycine (16), and 5-amino-2-hydroxypentanoic acid (22). The key step is the aldol dimerization and hemiaminal formation of cr-keto amide 26, which gives primarily protected anchinopeptolide D 27 under kinetically controlle d conditions. Cycloanchinopeptolide D (31) has been prepared by the unprece dented head-to-head photodimerization of the two hydroxystyrylamides of 4 u sing the hydrophobic effect in water to force the two side chains into clos e proximity so that [2 + 2] cycloaddition is faster than trans to cis doubl e bond isomerization. Coupling of amine 21 with pyroglutamic acid affords t he naturally occurring tripeptide 35, which had been assigned glutamic acid structure 34.