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 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

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.

Total Synthesis of (+)-Pochonin D and (+)-Monocillin II via Chemo- and Regioselective Intramolecular Nitrile Oxide Cycloaddition : Organic Letters 2017

Total Synthesis of (+)-Pochonin D and (+)-Monocillin II via Chemo- and Regioselective Intramolecular Nitrile Oxide Cycloaddition

Asymmetric total syntheses of (+)-pochonin D (1) and (+)-monocillin II (2), Hsp90 inhibitors with potent anticancer activity, have been accomplished where the macrolactone 3 was constructed through a chemo- and regioselective intramolecular nitrile oxide cycloaddition of diene 4.

Total Synthesis of Biselide E, a Marine Polyketide: Organic Letters 2017

Total Synthesis of Biselide E, a Marine Polyketide

The total synthesis of biselide E, a marine polyketide isolated from the Okinawan ascidian, has been accomplished. The highlight of this approach is the use of the β-elimination reaction of the chloroacetoxy group for the construction of an unstable six-membered α,β,γ,δ-unsaturated lactone portion at the late stage of the total synthesis.

Total Synthesis of Paralemnolide A: Organic Letters 2017

Total Synthesis of Paralemnolide A

The first total synthesis of tricyclic bisnorsesquiterpene paralemnolide A, isolated from the soft coral Paralemnalia thyrsoides, was achieved. This synthesis features the lactonization of the cyclohexene derivative having a tert-butyl ester via stereoselective epoxidation followed by treatment with a Brønsted acid and construction of the novel tricyclic skeleton by an intramolecular Reformatsky–Honda reaction.