Convenient in situ generation of various dichlorinating agents from oxone and chloride: diastereoselective dichlorination of allylic and homoallylic alcohol derivatives

A safe and convenient protocol was developed for in situ generation of various dichlorinating agents (cf. Cl-2, NCl3, Et-4 NCl3, ArICl2) from oxone and chloride. The synthetic utility of this protocol was demonstrated by diastereoselective dichlorination of a series of allylic and homoallylic alcohol derivatives with excellent yields and diastereoselectivity

Total Synthesis of Aculeatin A via Double Intramolecular Oxa-Michael Addition of Secondary/Tertiary Alcohols

A new synthetic strategy was developed for a concise total synthesis of aculeatin A as a single spiroisomer in both racemic and enantioselective fashions in 8-10 steps with similar to 10% overall yield from the known alkyne 11, featuring phenol oxidative dearomatization, double intramolecular oxa-Michael addition of secondary/tertiary alcohols, and chemo- and stereoselective reduction of ketone. The new synthetic strategy greatly expedites the access to the potent antiprotozoal aculeatin A, 6-epi-aculeatin D, and their analogues

A short and flexible route to tetrahydropyran-4-ones via conjugated nitrile oxides cycloaddition and oxa-Michael cyclization: a concise diastereoselective total synthesis of (+/-)-diospongin A

A short and flexible [3+2+1] synthetic strategy was developed for the synthesis of substituted tetrahydropyran-4-ones, featuring [3+2]-cycloaddition of alpha,beta-unsaturated nitrile oxides and alkenes and oxa-Michael cyclization in a 6-endo-trig fashion. The efficiency of this synthetic strategy was further demonstrated by the concise total synthesis of (+/-)-diospongin A in 8 steps with 20.2% yield

Cephalosporolide B Serving as a Versatile Synthetic Precursor: Asymmetric Biomimetic Total Syntheses of Cephalosporolides C, E, F, G, and (4-OMe-)G

Cephalosporolide B (Ces-B) was efficiently synthesized and exploited for the first time as a versatile biomimetic synthetic precursor for the chemical syntheses of not only cephalosporolides C, G, and (4-OMe-) G via a challenging diastereoselective oxa-Michael addition but also the structurally unprecedented cephalosporolides E and F via a novel biomimetic ring-contraction rearrangement. These findings provide the first direct chemical evidence that Ces-B may be the true biosynthetic precursor of cephalosporolides

Diastereoselective reductive ring expansion of spiroketal dihydropyranones to cis -fused bicyclic ethers

A novel double cascade synthetic strategy was developed for the diastereoselective syntheses of cis-fused bicyclic ethers, featuring cascade Achmatowicz rearrangement/spiroketalization and cascade spiroketal reduction/oxa-Michael cyclization. Especially, the chemo-, regio-, and diastereoselective reduction of densely functionalized spiroketal dihydropyranones, followed by oxa-Michael cyclization in a one-pot fashion, was achieved. © 2012 American Chemical Society

Biomimetic Asymmetric Total Syntheses of Spirooliganones A and B

Biomimetic total syntheses of potent antiviral spirooliganones A and B were achieved with 396 and 296 yield, respectively, in 12 steps from commercially available materials. The synthetic strategy was inspired primarily by the biogenetic hypothesis and was enabled by two independent cascade events: (i) an unprecedented reaction involving aromatic Claisen rearrangement/o-quinone methide formation/hetero-Diels-Alder cycloaddition to construct the tetracyclic framework and (ii) phenol oxidative dearomatization/spirocydization to build the spiro-fused cyclohexadienone/tetrahydrofuran moiety

Asymmetric Total Synthesis of (+)-Didemniserinolipid B via Achmatowicz Rearrangement/Bicycloketalization

A new synthetic strategy was developed for the asymmetric total synthesis of (+)-didemniserinolipid B in 19 linear steps, featuring a highly efficient and enantioselective construction of 6,8-dioxabicyclo[3.2.1]­octane (6,8-DOBCO) framework via a rarely explored Achmatowicz rearrangement/bicycloketalization strategy. In addition, the first total synthesis of the proposed (+)-didemniserinolipid C was accomplished with 41.6% yield in 4 steps from a common advanced intermediate <b>18</b>, and a possible revised structure of (+)-didemniserinolipid C was proposed. The new convergent synthetic strategy greatly expedites the entry to the didemniserinolipids and their analogues for biological activity evaluation

Total Synthesis of Purported Cephalosporolides H and I, Penisporolide B, and Their Stereoisomers

Development of a unified, bioinspired synthetic strategy to access four possible diastereomers of unique 2,2-dimethyl-[5,5]-spiroacetal-cis-fused-γ-lactone (Me₂SAFL) is reported, featuring pyridinium chlorochromate (PCC)-promoted oxidative ring expansion of β-hydroxy cyclic ethers and dehydrative ring-contraction rearrangement of 10-membered lactones. Synthetic utility of this strategy was demonstrated by total syntheses of 12 Me₂SAFLs, corresponding to the purported cephalosporolide H (CesH), cephalosporolide I (CesI), and penisporolide B (PenB) and their possible diastereomers. Comprehensive NMR data analysis suggested that the tricyclic Me₂SAFL core of CesH, CesI, and PenB should be revised to the same relative (3<i>R</i>*, 4<i>R</i>*, 6<i>S</i>*, 9<i>R</i>*) configuration and that the side chains required an unknown constitutional structure revision

Structural Revision of (+)-Uprolide F Diacetate Confirmed by Asymmetric Total Synthesis

A new structure for the cytotoxic cembranolide uprolide F diacetate (UFD) was proposed, and an enantioselective total synthesis was accomplished to confirm that our revised structure correctly represented the natural UFD and its absolute configuration. Our synthesis features a late-stage, highly efficient, and diastereoselective Nozaki–Hiyama–Kishi macrocyclization (95% yield) and an unexpected reagent-controlled reversible translactonization, which, being the first example within the cembranolide family, might have biogenetic implications and be of great importance to synthetic studies of the α-methylene-γ-lactone-bearing cembranolides