Application of the Claisen rearrangement to the synthesis of heterocyclic bicyclo[2,2,2]octenones: an approach to the morellins based on new biogenetic suggestions

Quillinan, A. J.; Scheinmann, F.

doi:10.1039/c29710000966

Cited by 44 publications

(45 citation statements)

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“…For those with the C8/C8a double bond, the orientation of H-15 at either the R-or -face was further confirmed by the 1 H and 13 C chemical shifts of the gem-dimethyl groups of the dihydrofuran unit. [1][2][3] In the case of the dihydrofurans with the -methine proton, such as scortechinone B (12), the gem-dimethyl groups appeared at similar δ H values, but distinctly different δ C values (∆δ C ca. 8 ppm).…”

Section: Resultsmentioning

confidence: 99%

Xanthone and Sesquiterpene Derivatives from the Fruits of Garcinia scortechinii

2005

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The fruits of Garcinia scortechinii afforded 10 new compounds: four caged-tetraprenylated xanthones (scortechinones Q−T, 1−4), four rearranged xanthones (scortechinones U−X, 5−8), and two sesquiterpene derivatives (scortechterpenes A, B, 9, 10), together with 14 known compounds: one sesquiterpene, two biflavonoids, and 11 caged-polyprenylated xanthones. Their structures were elucidated by analysis of spectroscopic data and comparison of the NMR data with those reported previously. All xanthone derivatives were evaluated for antibacterial activity against methicillin-resistant Staphylococcus aureus.

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Section: Resultsmentioning

confidence: 99%

Xanthone and Sesquiterpene Derivatives from the Fruits of Garcinia scortechinii

2005

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“…3). On the basis of the biosynthetic hypothesis of Quillinan and Scheinmann (15), compound 1a could arise from tris(dimethylallyloxy) precursor 17a, the xanthone motif of which could be traced to 1,3,5,6-tetrahydroxyxanthone 18. It is of interest to mention that 18 is also a natural product found in plants of the genus Hypericum (Guttiferae) (19,20).…”

Section: Resultsmentioning

confidence: 99%

Unified synthesis of caged Garcinia natural products based on a site-selective Claisen/Diels–Alder/Claisen rearrangement

Tisdale

Slobodov

Theodorakis

2004

Proc. Natl. Acad. Sci. U.S.A.

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A unified synthetic strategy toward caged Garcinia natural products has been designed and implemented. Central to the strategy is a tandem Claisen͞Diels-Alder͞Claisen rearrangement of a suitably substituted xanthone precursor to form forbesione (1a). Serving as a template, forbesione is then used to deliver representative members of this family, including desoxygaudichaudione A (4), desoxymorellin (5), and gambogin (10). Studies on the timing of this reaction cascade suggest that the C-ring Claisen͞Diels-Alder rearrangement proceeds initially and is followed by the A-ring Claisen reaction. The electronic and steric effects that govern the outcome of this cascade are presented.

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“…1:1, 70 % yield), which reacted with methylene phosphorane (MeP Upon heating in DMF at 120 8C, the methoxy derivative 7 entered into the expected Claisen rearrangement/DielsAlder cascade [3,8] leading through the indicated intermediate products to 6 and 6' in 47 and 42 % yields, respectively (Scheme 4). X-ray crystallographic analysis of 6' [9] (see ORTEP drawing, Scheme 4) revealed its structure, and, by extension, that of 6; both structures 6 and 6' were also supported by NOE studies (see Scheme 4). Selective removal of the acetonide group from 6 (TsOH, MeOH), followed by a two-step oxidation protocol (1) DMP, 2) NaClO 2 ), led to hydroxy carboxylic acid 22 in 91 % overall yield.…”

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confidence: 90%

“…Upon subsequent treatment with PPTS in refluxing benzene under azeotropic conditions, 24 led to 25 (Table 1) in 69 % yield, together with quinone 3, which was obtained in 11 % yield (Scheme 5). Pleasantly, compound 25 crystallized as beautiful yellow crystals whose X-ray crystallographic analysis [9] revealed its lateriflorone-like molecular architecture, including the correct stereochemistry at C3' (see ORTEP drawing, Scheme 5). However, an attempt to hydrolyze the enol methyl ether within 25 under acidic conditions (HCl (aq.…”

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confidence: 99%

Total Synthesis of 1‐O‐Methyllateriflorone

Nicolaou

Sasmal

et al. 2003

Angew Chem Int Ed

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With its unique spiroxalactone framework carrying a prenylated dihydrobenzoquinone moiety and a trioxatetracyclo [7.4.1.0 2,7 .0 2,11 ]tetradecane system, lateriflorone (1) represents an unusual synthetic challenge. Reported in 1999, this novel natural product [1] was isolated from the stem bark of Garcinia Lateriflora Bl (Guttiferae) collected from Indonesia, and it exhibits potent cytotoxicity against the P388 cancer cell line (ED 50 = 5.4 mg mL À1 ). Its seemingly fragile structure was secured by spectroscopic and X-ray crystallographic analysis. The secret of its stability, particularly at the spiroxalactonedihydroquinone junction, is probably due to the syn arrangement between the C2' proton and the C3' ester grouping which locks the leaving group in place, avoiding the belimination pathway that may lead to its rupture. The intriguing structural features of lateriflorone, coupled with its biological activity, prompted us to seek a possible pathway for its construction in the laboratory. Herein we report our findings thus far in this project, including the first total synthesis of 1-O-methyllateriflorone (2).We planned our synthesis of 1-O-methyllateriflorone (2) based on the expectation that the ester bond would be the easier bridge to forge between the two domains of the molecules. The retrosynthetic analysis began with the disconnection of the spiroxalactone moiety by rupturing its ethereal C À O bond, thus unraveling prenylated quinone 3 as a possible precursor (Scheme 1). The next rational disconnections, namely retro-aromatization of 3 and disassembly of its precursor 4 at the ester bond led to fragments 5 and 6 as suitable starting materials. Given our previous studies on forbesione, [2,3] a naturally occurring substance related to the present target, the cage ring system 6 [4] can be traced to the benzenoid compound 7. The coupling partner 5 can be obtained from a simple benzene derivative.The required prenylated 2,2'-dimethybenzopyran fragment 5 was synthesized as summarized in Scheme 2. Thus, 2,3-dihydroxybenzaldehyde (8) was selectively benzylated at the 3-position according to a literature procedure [5] to afford compound 9, which was converted into bromophenol 10 in 61 % overall yield by the following sequence: a) bromination para to the phenolic group; b) protection as a MOM ether, c) oxidation with m-CPBA; and d) cleavage of the resulting formate ester with NaHCO 3 (for abbreviations of reagents and protecting groups, see legends in schemes). Protection of the phenolic group in 10 as a TIPS ether to form 11 proceeded smoothly under standard conditions (TIPSCl, imid, 96 %). Boronation of 11 required premixing of the substrate with B(OiPr) 3 prior to addition of tBuLi in Et 2 O at À78 8C. The resulting borate derivative was then oxidized with H 2 O 2 under basic conditions (NaOH), and the resulting phenolic product was methylated to afford 12 in 76 % overall yield from 11. Scheme 1. Retrosynthetic analysis of lateriflorone (1).

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Application of the Claisen rearrangement to the synthesis of heterocyclic bicyclo[2,2,2]octenones: an approach to the morellins based on new biogenetic suggestions

Cited by 44 publications

References 2 publications

Xanthone and Sesquiterpene Derivatives from the Fruits of Garcinia scortechinii

Xanthone and Sesquiterpene Derivatives from the Fruits of Garcinia scortechinii

Unified synthesis of caged Garcinia natural products based on a site-selective Claisen/Diels–Alder/Claisen rearrangement

Total Synthesis of 1‐O‐Methyllateriflorone

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