Asymmetric Total Synthesis of (−)-Astakolactin and Confirmation of Its Stereostructure

Abstract

The originally proposed structure of astakolactin was revised, and an asymmetric total synthesis of the newly proposed structure was achieved. The key transformations in the synthesis were a Johnson-Claisen rearrangement, an asymmetric Mukaiyama aldol reaction, and a Mitsunobu-type cyclodehydration. The spectroscopic data and specific rotation of the compound obtained matched well with those reported for naturally occurring astakolactin.

Marine natural products

“…502 A large number of indole-containing alkaloids have been synthesised including makaluvamine O and batzelline D, 503 dictyodendrin G, 504 leucettamine C, 505 isonaamidine E, 506 and cylindradine B, 507 while both enantiomers of the bromotyrosine itampolin A have been produced. 508 Smenospongine A, 509 smenoqualone, 509,510 dehydrocyclospongiaquinone-1, 511 haterumadienone (done in a protecting group-free manner), 512 cheloviolenes A, B and dendrillolide C, 513 astakolactin (revised to 1217), 514 phorbaketal A, 515,516 alotaketals B, C and D, 516 and ansellones A, B and phorbadione 517 are all terpenoids that had syntheses published in 2017. One notable synthetic campaign was published by Kishi's group.…”

Eight-Membered Rings With One Oxygen Atom

“…157 Meanwhile, 3 years later, the same group revised the structure of astakolactin to a pyran derivative 182a. 158 Yamaguchi lactonization was the key step in the stereoselective synthesis of the eight-membered lactone (+)-cephalosporolide D 185. It involved the reaction of acid 183 in the presence of N,N-diisopropylethylamine (DIPEA), 2,4,6-trichlorobenzoyl chloride and DMAP in benzene for the construction of the macrolactone 184 and subsequent removal of the protecting group in acid conditions (Scheme 24).…”