•A novle synthesis of thiochromanyl-spirooxindoles was achieved in mild conditions.•25 spirooxindoles were obtained in good yields and diastereoselectivities.•The reaction system can be enlarged to gram-scale efficiently.A facile method for the synthesis of thiochromanyl-spirooxindoles via sulfa-Michael/Aldol reaction of 3-ylideneoxindoles with thiosalicylaldehydes has been developed. This tandem reaction, which tolerates a wide variety of functional groups, furnished diverse substituted functional thiochromanyl-spirooxindoles in up to 90% yields with good diastereoselectivities. Furthermore, the reaction system could be promoted to gram-scale efficiently under the mild conditions.Download high-res image (140KB)Download full-size image

A new access to spiro[5.5]undecane frameworks was reported through the ZnMe2-promoted alkynylation of salicylaldehyde and HCO2H-mediated dearomatizative cyclization which can be used to construct an all-carbon quaternary spirocenter. This method can be applied to the rapid synthesis towards a series of useful motifs of natural products, such as the core of elatol and aphidicolin.

We herein reported a novel Mg(ClO4)2-promoted intermolecular [4 + 3] cycloaddition reaction of oxindole derivatives and cyclopentadiene. This new strategy provides a convenient approach to the concise synthesis of a series of spirocycloheptane oxindole derivatives, with moderate to good yields and high diastereoselectivities.

A visible-light induced photocatalytic aerobic oxidative dehydrogenative coupling/aromatization tandem reaction of glycine esters with unactivated alkenes has been accomplished. This visible light-driven protocol has been successfully applied to a broad scope of glycine esters and simple alkenes, giving rise to diverse substituted quinoline derivatives in 18–84% yield under mild (at room temperature under air atmosphere) and operationally simple reaction conditions.

A tandem reaction consisting of a copper(I)-catalyzed cycloetherification and a hydrogen-bond-induced inverse-electron-demand oxa-Diels–Alder cycloaddition was performed from chiral propargyl alcohol, generating several kinds of optically pure [5, 6] spiroketals in excellent stereoselectivities and yields. The investigation on mechanism found that the cyclization prompted by a hydrogen bond not only improved the efficiency but also determined the diastereoselectivity.

A concise and facile synthetic protocol for the construction of the 2-γ-lactone chromanone skeleton has been achieved through a TMSI-promoted diastereoselective vinylogous Michael addition of siloxyfuran to 2-substituted chromones. The applicability of this method is demonstrated through the rapid access to the total syntheses of (±)-microdiplodiasone, (±)-lachnone C, and (±)-gonytolides C and G.

Ivorenolide B (1), an unprecedented 17-membered macrolide featuring conjugated acetylenic bonds and four chiral centers, was isolated from Khaya ivorensis. The structure of 1 was fully determined by spectroscopic analysis and total syntheses of its four most possible stereoisomers. Compound 1 showed significant immunosuppressive activity.

A series of structurally related analogues of the natural product paracaseolide A were synthesized and identified as potent PTP1B inhibitors. Among these analogues, compound 10 in particular showed improved PTP1B enzyme inhibitory activity, high selectivity for PTP1B over TC-PTP, and improved cellular effects.

A novel formal asymmetric synthesis of (−)-triptonide and (−)-triptolide, featuring a new alternative access to their known key intermediate 4, has been achieved through two synthetic routes in 9 steps with 13.6% total yield and 10 steps with 18.5% overall yield, respectively. This synthesis is scalable and hence has high potential for application to further synthetic elaboration and biologic investigation on such natural products.

A new and facile tandem reaction of intramolecular hydroamination and novel [4 + 3] cycloaddition was developed for the synthesis of multitudinal indole-containing 5,7,6-tricyclic skeletons. This method was further extended to the quick synthesis of a series of useful motif of natural products, such as the core of ervatamine and silicine.

A direct asymmetric tandem reaction of α-nitro ketones with β,γ-unsaturated α-ketoesters was found to be catalyzed by a bifunctional rosin-derived thiourea and gave 5-nitro-2-actoxyl-2-pentenates in excellent ee values and yields, a much better result than previously reported. Furthermore, through theoretical analysis, literature research and experimental verifications, a new mechanism involving an inverse-electron-demand Diels–Alder (IEDDAR) and a retro-Henry reaction was proposed.Graphical abstract. A direct asymmetric tandem reaction of α-nitro ketones with β,γ-unsaturated α-ketoesters was found to be catalyzed by a bifunctional rosin-derived thiourea and gave 5-nitro-2-actoxyl-2-pentenates in excellent ee values and yields, a much better result than previously reported. Furthermore, through theoretical analysis, literature research and experimental verifications, a new mechanism involving an inverse-electron-demand Diels–Alder (IEDDAR) and a retro-Henry reaction was proposed.

The first total synthesis of aphadilactones A–D, diastereomeric natural products recently isolated from the Meliaceae plant Aphanamixis grandifolia by Yue and co-workers, which possess an unprecedented carbon skeleton, has been achieved. The synthesis features a catalytic asymmetric hetero-Diels–Alder reaction to form the dihydropyran ring, concurrent installation of the lactone and furan moieties via a tandem acid-catalyzed acetal cleavage, oxidation, and cyclization process, and an intermolecular Diels–Alder reaction to forge the target products.

Transition-metal-catalyzed spiroketalization cyclization has been performed successfully and has led to the first total synthesis of (±)-δ-rubromycin with a longest linear sequence of 18 steps from commercially available guaiacol in a 2.7% overall yield.

The first enantioselective total synthesis of (+)-coriandrone A and B, two bioactive natural products, has been achieved in 10 steps and 11 steps starting from commercially available methyl 2-hydroxy-4-methoxybenzoate. Key reactions include a Claison rearrangement, a Shi-type epoxidation–cyclization sequence and ortho-metallation of t-butylbenzamides with (S)-(−)-propylene oxide reaction.

Ivorenolide A (1), a novel 18-membered macrolide featuring conjugated acetylenic bonds and five chiral centers, was isolated from Khaya ivorensis. The structure of 1 was fully determined by spectroscopic analysis, single-crystal X-ray diffraction, and bioinspired total synthesis. Both compound 1 and its synthetic enantiomer 2 showed potent and selective immunosuppressive activity.

A new synthesis of γ-rubromycin is presented through a new oxidative, bisbenzannulated spiroketalization as a key step which is catalyzed by an in situ generated hypoiodite species, developed previously by our group. This key transformation has high efficiency and convenient conditions. This is a new and efficient catalytic application for organohypoiodine reagents.

A new [4 + 3]-cycloaddition between benzofuran allylic alcohols and dienes, promoted by camphorsulfonic acid, has been identified. A novel strategy which used this cycloaddition as a key step has been developed for the synthesis of 6,7,5-tricyclic skeleta, and syntheses toward frondosin B (1) and 5-epi-liphagal (2) have been achieved via short routes in good yields.

An approach is developed for the synthesis of bisbenzannelated spiro[5,5]ketals via a catalytic relay reaction cascade involving a new cyclo-etherification, which is prompted by fluoride and catalyzed by the hypoiodite species generated in situ from irradiative aerobic oxidation of an iodide ion formed in the former step of the reaction cascade.

A new catalytic application of hypoiodite reagents generated in situ from iodide ions is found, which succeeded in the synthesis of bisbenzannelated spiroketal cores for the first time. Fluoride was proven to be obligatory for this spiroketalization, which is the first fluoride-promoted oxidative cycloetherification to aromatic spiroketals.

Paricalcitol, an analog of vitamin D, is used as a drug for the prevention and treatment of secondary hyperparathyroidism. In this paper, a new strategy for the synthesis of paricalcitol is described. This approach includes three main improvements: one-pot regioselective ozonization cleavage of the side-chain and methylene at C-19, free-radical reduction removal of the OH group formed at C-19, and side-chain assembly using a Wittig reaction. These are all new strategies for the synthesis of 19-nor-vitamin D2 compounds.

Unexpected products containing acyl-substituted unsaturated seven-membered carbocycle were synthesized by FeCl3-promoted intramolecular Prins cyclization of alkynyl-dimethylacetals in good yields. It is remarkable that the synthesized 7-exocyclic vinyl cations generated as a result of Prins-type cyclization were trapped by H2O (no halogen ion) in CH2Cl2 to give the corresponding enol derivatives. Those enol derivatives underwent enol-keto tautomerism and then eliminated one molecule of MeOH to give the corresponding acyl-substituted unsaturated seven-membered carbocycle.

The first total syntheses of bipinnatone A and B have been achieved starting from commercially available phloroglucinol, p-hydroxybenzaldehyde in ten steps. Key features of the syntheses include Aldol reaction, aryl-alkylation and InCl3–NaBH4 selective reduction.

Simple organic nitrogen bases, such as Et3N, pyridine, DBU, etc., were found to be convenient and useful reagents for deprotection of TBDMS groups on acidic hydroxyl groups. The efficiency of these bases has an apparent order: 1° amine > 2° amine > 3° amine and aliphatic base > aromatic base. In aqueous DMSO and at room temperature, phenolic TBDMS ethers were removed selectively in the presence of alcoholic TBDMS ethers. And catalytic base can make these reactions complete. This method is high-yielding, fast, clean, safe and cost-effective.

Two novel steroid-linked nitrogen mustard conjugates 1a and 1b were synthesized by using estrogenic acid 4 coupled with aniline mustard 8 and phenol mustard 13 in an esterification or amidation procedure. Preliminary cytotoxic screening on cancer cell lines in vitro showed that, the steroid-ester linked nitrogen mustard conjugate 1a exhibited obvious increasing of activities.

An alternative approach to synthesize pedamide, a key building block of pederin was described. Iodine-induced asymmetric heterocyclization was used as the key step to construct the skeleton, a tetrahydropyran ring with three chiral centers. Brown's asymmetric allylation and Lewis acid-mediated allylation were investigated to introduce chains and chiral alcohols. Sharpless dihydroxylation decorated the side chain. And high optically pure target was obtained by removing the epimers formed in these reactions on column chromatography.

The natural mosquito attractant pheromone, (−)-(5R,6S)-6-acetoxyhexadecan-5-olide 1, was synthesized from readily available aldehyde 3 and cyclopentanone 4 using l-proline catalyzed asymmetric aldol reactions as the key step.(2R)-2-[1′-(S)-Hydroxyundecyl]-cyclopentanoneC16H30O2Ee = 96%[α]D = −33.5 (c 0.7, CHCl3)Source of chirality: l-proline catalyzed asymmetric aldol reactionAbsolute configuration: 2R,1′S(2S)-2-[1′-(S)-Hydroxyundecyl]-cyclopentanoneC16H30O2Ee = 70%[α]D = +36.9 (c 1.05, CHCl3)Source of chirality: l-proline catalyzed asymmetric aldol reactionAbsolute configuration: 2R,1′S(2R)-2-[1′-(S)-Tributyldimethylsilyloxylundecyl]cyclopentanoneC22H44O2SiEe = 96%[α]D = −49 (c 1.70, CHCl3)Source of chirality: l-proline catalyzed asymmetric aldol reactionAbsolute configuration: 2R,1′S(2R)-2-[1′-(S)-Acetoxyundecyl]cyclopentanoneC18H32O3Ee = 96%[α]D = −42 (c 0.80, CHCl3)Source of chirality: l-proline catalyzed asymmetric aldol reactionAbsolute configuration: 2R,1′S(5R,6S)-6-Hydroxyhexadecan-5-olideC16H30O3Ee = 96%[α]D = −11 (c 1.50, CHCl3)Source of chirality: l-proline catalyzed asymmetric aldol reactionAbsolute configuration: 5R,6S(−)-(5R,6S)-6-Acetoxy-hexadecan-5-olideC18H32O4Ee = 96%[α]D = −36.9 (c 1.05, CHCl3)Source of chirality: l-proline catalyzed asymmetric aldol reactionAbsolute configuration: 5R,6S

A novel 2-D coordination polymer [Mn2(pdc)2(H2O)3]n2nH2O (pdc=pyridine-2,3-dicarboxylate) 1 has been hydrothermally synthesized and characterized by the elemental analyses, IR spectrum, TG analysis along with the single crystal X-ray diffraction. Colorless platelet crystals of compound 1 crystallize in the monoclinic system, space group C2/c, a=23.900(5) Å, b=8.581(2) Å, c=19.833(4) Å, β=106.51(3)°,V=3899.8(15) Å3, Z=8 and R=0.0425. The title compound consists of two kinds of MnII center with different coordination environments by pdc and water ligands, to form a 2-D sheet, and then constructs a 3-D network by interlayer hydrogen bonds.

A series of structurally related analogues of the natural product paracaseolide A were synthesized and identified as potent PTP1B inhibitors. Among these analogues, compound 10 in particular showed improved PTP1B enzyme inhibitory activity, high selectivity for PTP1B over TC-PTP, and improved cellular effects.

A novel formal asymmetric synthesis of (−)-triptonide and (−)-triptolide, featuring a new alternative access to their known key intermediate 4, has been achieved through two synthetic routes in 9 steps with 13.6% total yield and 10 steps with 18.5% overall yield, respectively. This synthesis is scalable and hence has high potential for application to further synthetic elaboration and biologic investigation on such natural products.

A new catalytic application of hypoiodite reagents generated in situ from iodide ions is found, which succeeded in the synthesis of bisbenzannelated spiroketal cores for the first time. Fluoride was proven to be obligatory for this spiroketalization, which is the first fluoride-promoted oxidative cycloetherification to aromatic spiroketals.

The first enantioselective total synthesis of (+)-coriandrone A and B, two bioactive natural products, has been achieved in 10 steps and 11 steps starting from commercially available methyl 2-hydroxy-4-methoxybenzoate. Key reactions include a Claison rearrangement, a Shi-type epoxidation–cyclization sequence and ortho-metallation of t-butylbenzamides with (S)-(−)-propylene oxide reaction.