Synthesis and Biological Evaluation of ABCD Ring Fragments of the Kibdelones

Abstract

Arylation goes platinum: The synthesis of the ABCD ring fragments of the kibdelones has been achieved through a novel PtIV‐catalyzed arylation of a quinone monoketal followed by photocyclization (see scheme). Biological evaluation in the NCI 60‐cell screen revealed that the kibdelone ABCD ring analogues were about 2000 times less active than kibdelones B and C, suggesting that the tetrahydroxanthone structure of the kibdelones is crucial for cytotoxicity.

Synthesis and Biological Evaluation of Kibdelone C and Its Simplified Derivatives

“…This observation indicated that our synthetic material was enantiomeric to the natural product, a conclusion consistent with contemporaneous results from the Porco group. 15b …”

“…12,13 The Suzuki group made an important contribution to the area with a synthesis of FD-594 aglycone; theirs was the first enantioselective synthesis of a member of the family. 14 The Porco group reported an elegant synthesis of the naturally occurring (+)-kibdelone C, 15 and we described a synthesis of (−)-simaomicin α in 2013. 16 More recently, the Martin group recently described a total synthesis of the aglycone of IB-00208.…”

A divergent route to 9,10-oxygenated tetrahydroprotoberberine and 8-oxoprotoberberine alkaloids: synthesis of (±)-isocorypalmine and oxypalmatine

“…Thereafter reaction of 13 with n -butyllithium in the presence of dimethylmalonate gave diester 14 . 21,22 This reaction presumably proceeds via nucleophilic attack of malonate anion on a benzyne intermediate generated from dehydrobromination of 13 . 23 Selective hydrolysis of the aliphatic ester group was accomplished with K 2 CO 3 in refluxing H 2 O:MeOH to give acid 15 .…”

Total Synthesis and Absolute Stereochemical Assignment of Kibdelone C

“…In our retrosynthetic analysis, we envisioned that the congener kibdelone C 3 may be obtained from merger of ABCD fragment 12 4 and 2-iodo-1-cyclohexenecarboxylate fragment 13 . In order to access the tetrahydroxanthone ring-system, we envisioned use of an oxa -Michael/retro-Michael 5 Friedel-Crafts annulation sequence.…”

“…Fragment 12 may be derived from Pt(IV)-catalyzed arylation of quinone monoketal 10 and hydroxystyrene 11 . 4 We envisioned that the chiral EF ring fragment 13 may be obtained from diastereoselective, intramolecular halo-Michael aldol reaction of aldehyde ynoate 14 , the latter derived from protected diol 15 . There are numerous literature reports describing intermolecular reactions of preformed β-iodoallenoates reacting with aldehydes 7 including a recent report by Frontier and coworkers describing an intramolecular variant with an alkynone substrate.…”