Unified Asymmetric Total Syntheses of (−)‐Alotaketals A–D and (−)‐Phorbaketal A

Abstract

The novel tricyclic spiroketal alotane-type sesterterpenoids showed strikingly different biological activities and potency with subtle structural alterations. Asymmetric total syntheses of the tricyclic sesterterpenoids (-)-alotaketals A-D and (-)-phorbaketal A were accomplished [29-31 steps from (-)-malic acid] in a collective way for the first time. The key features of the strategy included 1) a new cascade cyclization of vinyl epoxy δ-keto-alcohols to forge the common tricyclic spiroketal intermediate, 2) a late-stage allylic C-H oxidation, and 3) olefin cross-metathesis to install the different side chains.

Total Synthesis of Xanthoangelol B and Its Various Fragments: Toward Inhibition of Virulence Factor Production of Staphylococcus aureus

“…13 C NMR (100 MHz, CDCl 3 ) δ 145.8, 131.5, 124.1, 109.7, 37.8, 26.3, 25.6, 22.7, 22.4, 17.6. Data are consistent with those reported in ref (60).…”

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.…”

Advances in polycyclization cascades in natural product synthesis

“…Tong and co-workers used this concept to promote the cyclization of a vinylepoxy-δ-keto-alcohol (VEKA) 28 (Scheme 6) to forge the common tricyclic spiroketal core of several members of the alotaketal family. 19 The cascade commenced with triene 29, desilylation of which with HF•Py, then chemoselective epoxidation of the most substituted alkene (on the less-hindered face) with dimethyldioxirane (DMDO), afforded the unstable VEKA 28 (10:1 dr). Treatment of 28 with triflic acid triggered the cyclization cascade via protonated epoxide 30, which underwent an SN2' ring-opening by the proximal hemiketal, generating the tricyclic spiroketal 31 in good yield on multigram scale (56% over three steps).…”