Total Synthesis of the Sesquiterpenoid Periconianone A Based on a Postulated Biogenesis : JACS 2017

Total Synthesis of the Sesquiterpenoid Periconianone A Based on a Postulated Biogenesis

The first enantioselective total synthesis of the complex tricarbocyclic sesquiterpenoid periconianone A based on a postulated biogenesis is reported. Key elements of the synthetic route include the use of an isopropenyl group as a removable directing group for stereoselective synthesis, a sequence featuring a Rh-mediated O–H insertion/[3,3]-sigmatropic rearrangement and subsequent α-ketol rearrangement, and a late stage aldol reaction to furnish the complex cage-like framework.

Article: DOI: 10.1021/jacs.7b10053

Total Synthesis of (−)-Geissoschizol through Ir-Catalyzed Allylic Amidation as the Key Step: OL 2017

Total Synthesis of (−)-Geissoschizol through Ir-Catalyzed Allylic Amidation as the Key Step

The iridium-catalyzed, Zn(OTf)2 promoted asymmetric allylic amidation of a secondary alcohol derived from tryptamine has been utilized to forge a tetrahydro-β-carboline. Based on this key step, a novel, facile, and enantioselective total synthesis of (−)-geissoschizol was achieved in 10 steps.

More Information: http://pubs.acs.org/doi/10.1021/acs.orglett.7b03133

Synthesis of the ABC Substructure of Brevenal by Sequential exo-Mode Oxacyclizations of Acyclic Polyene Precursors: Org Lett 2017

Synthesis of the ABC Substructure of Brevenal by Sequential exo-Mode Oxacyclizations of Acyclic Polyene Precursors

Exploratory studies on the sequential exo-mode oxacyclizations of acyclic polyene precursors have provided a substantial substructure of brevenal, including the fused tricyclic polyether with stereochemical patterns consistent with the AB and BC ring fusions. The synthesis of acyclic substrates featured two variations of Cr(II)/Ni(II) couplings for preparing 1,1-disubstituted allylic alcohols. A sequence of iodine-promoted cycloetherification, base-promoted intramolecular conjugate addition, and mercury-promoted cycloetherification produced the tricyclic substructure.

Synthetic Route to Oscillatoxin D and Its Analogues: OL 2017

Synthetic Route to Oscillatoxin D and Its Analogues

O-Methyloscillatoxin D and its analogues were concisely synthesized by a bioinspired intramolecular Mukaiyama aldol reaction as a key step, which involves the construction of a novel spiro-ether moiety.

Synthesis and Anticancer Evaluation of 2,3-Disubstituted Indoles Derived from Azobenzenes and Internal Olefins: EJOC 2017

Synthesis and Anticancer Evaluation of 2,3-Disubstituted Indoles Derived from Azobenzenes and Internal Olefins
Azo-directed rhodium(III)-catalysed C–H functionalization and intramolecular annulation reactions between azobenzenes and internal olefins are described. This transformation leads to 2,3-disubstituted free (NH)-indoles with excellent site-selectivity and functional-group compatibility. The resulting indoles were evaluated for in-vitro anticancer activity against human endometrial adenocarcinoma cells (Ishikawa), triple negative human breast cancer cells (MDA-MB-231), and human renal cancer cells (Caki-1). 2,3-Disubstituted indoles 3b, 3k, and 5b were found to show potent cytotoxic effects that were competitive with the anticancer agent doxorubicin.

Synthesis of Alfaprostol and PGF2α through 1,4-Addition of an Alkyne to an Enal Intermediate as the Key Step: OL 2017

Synthesis of Alfaprostol and PGF2α through 1,4-Addition of an Alkyne to an Enal Intermediate as the Key Step

The veterinary drug Alfaprostol and prostaglandin PGF2α have been synthesized in just nine steps. The strategy involved the conjugate addition of an alkyne to a bicyclic enal, available in three steps by a proline-catalyzed aldol reaction of succinaldehyde. In the case of Alfaprostol, this resulted in the shortest synthesis reported to date. For PGF2α, this approach improved our previous route by making the 1,4-addition and ozonolysis more operationally simple

Cyclopropane Intermediates from Insertion Reactions of Platinum–Carbenes: A Route to Heterospiranes: Synlett 2017

Cyclopropane Intermediates from Insertion Reactions of Platinum–Carbenes: A Route to Heterospiranes

Heteroaromatic-anchored enynals with a pendent alkene group were successfully cyclized through a Huisgen-type [3+2] cycloaddition to give a tetracyclic Pt–carbene complex that underwent insertion into the C–H bond in the β-position to give fused cyclopropanes that are otherwise inaccessible. On heating, the cyclopropanes smoothly rearranged to form the corresponding heterospiranes with excellent levels of stereoselectivity and high yields.

Intramolecular Keto Lactam Condensation: A Convenient and Straightforward Approach to Bicyclic Vinylogous Lactams: EJOC 2017

Intramolecular Keto Lactam Condensation: A Convenient and Straightforward Approach to Bicyclic Vinylogous Lactams

Although the aldol condensation is a well-known reaction, the aza-type aldol condensation, namely, the intramolecular condensation of common keto lactams leading to bicyclic vinylogous lactams, is a highly demanding transformation, with potential applications in both organic synthesis and medicinal chemistry. The known methods for this type of cyclization require several steps. In this paper, we disclose a straightforward approach that consists of the in-situ formation of silyl enol ethers with tert-butyldimethylsilyl trifluoromethanesulfonate (TBDMSOTf), lactam activation with triflic anhydride (Tf2O), and a tandem cyclocondensation reaction. The reaction can be run in a one-pot manner or in a two-step fashion, both under mild conditions. The yields for the one-pot version were 52–80 %. In some cases, the two-step version gave higher overall yields (44–85 %) than the one-pot version.

Total Synthesis of Lycoricidine and Narciclasine by Chemical Dearomatization of Bromobenzene: ACIE 2017

Total Synthesis of Lycoricidine and Narciclasine by Chemical Dearomatization of Bromobenzene




The total synthesis of lycoricidine and narciclasine is enabled by an arenophile-mediated dearomative dihydroxylation of bromobenzene. Subsequent transpositive Suzuki coupling and cycloreversion deliver a key biaryl dihydrodiol intermediate, which is rapidly converted into lycoricidine through site-selective syn-1,4-hydroxyamination and deprotection. The total synthesis of narciclasine is accomplished by the late-stage, amide-directed C−H hydroxylation of a lycoricidine intermediate. Moreover, the general applicability of this strategy to access dihydroxylated biphenyls is demonstrated with several examples.

Cobalt versus Osmium: Control of Both trans and cis Selectivity in Construction of the EFG Rings of Pectenotoxin 4: ACIE 2017

Cobalt versus Osmium: Control of Both trans and cisSelectivity in Construction of the EFG Rings of Pectenotoxin 4

Catalytic oxidative cyclisation reactions have been employed for the synthesis of the E and F rings of the complex natural product target pectenotoxin 4. The choice of metal catalyst (cobalt- or osmium-based) allowed for the formation of THF rings with either trans or cis stereoselectivity. Fragment union using a modified Julia reaction then enabled the synthesis of an advanced synthetic intermediate containing the EF and G rings of the target.

Total synthesis of (+)-blennolide C and (+)-gonytolide C via spirochromanone: Tetrahydron Letters 2017

Total synthesis of (+)-blennolide C and (+)-gonytolide C via spirochromanone

We report the asymmetric total synthesis of (+)-blennolide C and (+)-gonytolide C isolated from endophytic fungi. The synthesis involved construction of a spirochromanone with a chiral quaternary carbon by the aldol reaction of o-hydroxyacetophenones and optically active α-oxygenated cyclohexenone, followed by cyclization under acidic conditions. Oxidative cleavage of the alkene moiety of the spirochromanone furnished the chromanone diester. Through treating the diester with a Lewis acid, the first total synthesis of (+)-blennolide C was achieved by deprotecting the oxygen functionality of the diester and simultaneous Dieckmann condensation. Total synthesis of (+)-gonytolide C was also achieved by lactone formation from the deprotected diester.

Total Synthesis and Anti-inflammatory Evaluation of Penchinone A and Its Structural Analogues: JOC 2017

Total Synthesis and Anti-inflammatory Evaluation of Penchinone A and Its Structural Analogues

The first total synthesis and biological evaluation of penchinone A and its structural analogues are described. The key steps for the preparation of penchinone A derivatives involve the oxime-directed palladium(II)-catalyzed oxidative acylation, Claisen rearrangement, and base-mediated olefin migration. This transformation efficiently provides a range of allyl-substituted biaryl ketones with site-selectivity and functional group compatibility. In addition, all synthetic compounds were screened for anti-inflammatory activity against nitric oxide (NO), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) with lipopolysaccharide (LPS)-induced RAW264.7 cells. Generally, a range of penchinone A derivatives potently inhibited NO, TNF-α, and IL-6 productions, compared to dexamethasone as a positive control. Notably, penchinone A (8g) and its derivatives (8e and 8f) were found to exhibit anti-inflammatory activity stronger than that of dexamethasone.

Total Synthesis of Longeracinphyllin A: JACS 2017

Total Synthesis of Longeracinphyllin A

The first and asymmetric total synthesis of longeracinphyllin A, a hexacyclic Daphniphyllumalkaloid, has been accomplished. A tetracyclic intermediate was prepared through silver-catalyzed alkyne cyclization and Luche radical cyclization. A phosphine-promoted [3 + 2] cycloaddition reaction was exploited to construct the sterically congested E ring bearing vicinal tertiary and quaternary centers. The cyclopentenone motif was assembled by using intramolecular Horner–Wadsworth–Emmons olefination. Raney Ni reduction delivered the tertiary amine from a thioamide precursor at a late stage.