831227-95-3

Upstream product

• 21624-36-2 humulene 9,10-epoxide 
• 531492-87-2 (9E)-humulene-2,3;6,7-diepoxide 
• 6753-98-6 α-caryophyllene 
• 13877-94-6 (-)-beta-Caryophyllene epoxide 
• 1139-30-6 caryophyllene oxide 
• 77647-45-1 (1R)-5c,6t-epoxy-2ξ,6c,10,10-tetramethyl-(1r,9t)-bicyclo[7.2.0]undecane 
• 87-44-5 β-caryophyllene 
• 60545-11-1 2S*,3S*,6S*,7S*,9S*,10S*-humulene 2,3;6,7;9,10-triepoxide 

Downstream Products

• 80408-11-3 Humulenol-II 
• 24405-90-1 (4E,8E)-2,6,6,9-tetramethyl cycloundeca-4,8-dienone 

Relevant academic research and scientific papers

Development of a Terpenoid Alkaloid-like Compound Library Based on the Humulene Skeleton

Many natural terpenoid alkaloid conjugates show biological activity because their structures contain both sp3-rich terpenoid scaffolds and nitrogen-containing alkaloid scaffolds. However, their biosynthesis utilizes a limited set of compounds as sources of the terpenoid moiety. The production of terpenoid alkaloids containing various types of terpenoid moiety may provide useful, chemically diverse compound libraries for drug discovery. Herein, we report the construction of a library of terpenoid alkaloid-like compounds based on Lewis-acid-catalyzed transannulation of humulene diepoxide and subsequent sequential olefin metathesis. Cheminformatic analysis quantitatively showed that the synthesized terpenoid alkaloid-like compound library has a high level of three-dimensional-shape diversity. Extensive pharmacological screening of the library has led to the identification of promising compounds for the development of antihypolipidemic drugs. Therefore, the synthesis of terpenoid alkaloid-like compound libraries based on humulene is well suited to drug discovery. Synthesis of terpenoid alkaloid-like compounds based on several natural terpenoids is an effective strategy for producing chemically diverse libraries.

Scalable Total Synthesis of (-)-Triptonide: Serendipitous Discovery of a Visible-Light-Promoted Olefin Coupling Initiated by Metal-Catalyzed Hydrogen Atom Transfer (MHAT)

An efficient and scalable total synthesis of (-)-triptonide is accomplished based on a metal-catalyzed hydrogen atom transfer (MHAT)-initiated radical cyclization. During the optimization of the key step, we discovered that blue LEDs significantly promoted the efficiency of reaction initiated by Co(TPP)-catalyzed MHAT. Further exploration and optimization of this catalytic system led to development of a dehydrogenative MHAT-initiated Giese reaction.

Stereochemical characterisation of the non-canonical α-humulene synthase fromAcremonium strictum

The non-canonical fungal α-humulene synthase was investigated through isotopic labelling experiments for its stereochemical course regarding inversion or retention at C-1, the face selectivity at C-11, and the stereoselectivity of the final deprotonation. A new and convenient desymmetrisation strategy was developed to enable a full stereochemical analysis of the catalysed steps to the achiral α-humulene product from stereoselectively labelled farnesyl diphosphate.

An ultrathin amino-acid based copper(II) coordination polymer nanosheet for efficient epoxidation of β-caryophyllene

Natural amino acids are important building blocks for the construction of intriguing coordination polymers (CPs) because of their abundance, inexpensiveness and environmental benignness. Herein, two copper(II) CPs, namely, 2D CuIle-e nanosheet (e: ethanol) and 1D CuIle-m nanoshuttle (m: methanol), were fabricated from L-isoleucine (Ile) and well characterized with single-crystal x-ray diffraction, XPS spectra, TEM and AFM, etc. More importantly, two novel and stable catalytic nanosystems, i.e. CuIle-e/acetone/TBHP (tert-butyl hydroperoxide) and CuIle-e/THF/O2/TBHP, were thus conveniently built by using ultrathin 2D CuIle-e nanosheet (~ 2.3 nm) in suitable aprotic solvents. Under mild conditions, complete conversion of β-caryophyllene and good yields (86.1% or 87.2%) for β-caryophyllene epoxide were gained via CuIle-e/acetone/TBHP or CuIle-e/THF/O2 (1 atm)/TBHP (10.0 mol%), respectively. Notably, ultrathin CuIle-e nanosheet showed fairly satisfactory stability, which may open a unique window for the facile fabrication of new amino-acid based CP nanosystems with outstanding catalytic performances in actual applications.

Organocatalytic epoxidation and allylic oxidation of alkenes by molecular oxygen

Pyrrole-proline diketopiperazine (DKP) acts as an efficient mediator for the reduction of dioxygen by Hantzsch ester under mild conditions to allow the aerobic metal-free epoxidation of electron-rich alkenes. Mechanistic crossovers are underlined, explaining the dual role of Hantzsch ester as a reductant/promoter of the DKP catalyst and a simultaneous competitor for the epoxidation of alkenes when HFIP is used as a solvent. Expansion of this protocol to the synthesis of allylic alcohols was achieved by adding a catalytic amount of selenium dioxide as an additive, revealing a superior method to the classical application of t-BuOOH as a selenium dioxide oxidant.

Ionic liquid-mediated catalytic oxidation of β-caryophyllene by ultrathin 2D metal-organic framework nanosheets under 1 atm O2

An ionic liquid (IL)-mediated facile method was established for the epoxidation of β-caryophyllene with molecular oxygen using ultrathin (～3?6 nm) 2D Cu-, Co- or Ce-based MOF nanosheets. Under the optimum conditions, high selectivity (92.4percent) and excellent yield (86.7percent) for β-caryophyllene epoxide were obtained over ultrathin (～5.5 nm) Cu-TCPP nanosheets (TCPP = tetrakis(4-carboxyphenyl)porphyrin) with the aid of [C12mim]Cl at 313 K and 1 atm O2. Notably, a small amount of [C12mim]Cl (1-dodecyl-3-methylimidazolium chloride, 5.0 mol percent) played pivotal roles in forming a favorable microenvironment in-situ, thus significantly improving the catalytic performances of above-mentioned Cu-TCPP nanosheets containing PVP stabilizer. Moreover, ultrathin Cu-TCPP nanosheets showed better stability during β-caryophyllene transformation in the presence of amphiphilic [C12mim]Cl, as supported by TEM and XRD analyses. Importantly, the addition of TBHP (tert-butyl hydroperoxide, 13.0 mol percent) initiator is also crucial for the aerobic oxidation of β-caryophyllene via Cu-TCPP nanosheets/[C12mim]Cl/TBHP/O2 nanosystem. Further insights into the synergistic effects and free radical mechanism were achieved by fluorescence, DRUV-Vis, UV-vis and XPS measurements.

Erratum: Removal of the E-Olefin Barrier of Humulene Leading to Unnatural Terpenoid-like Skeletons (Organic Letters (2018) 20, 22, (7313-7320) DOI: 10.1021/acs.orglett.8b03259)

The structures of compounds 11 and 12 shown in Figure 2A were corrected by changing the relative configurations, although the structures in the Supporting Information were correct. Figure 2A is corrected as follows: The absolute configurations of compounds 15-19 drawn in Figure 3A and in the Supporting Information were corrected. Although the relative configurations shown in the Supporting Information were correct, the wrong assignment is because of drawing the absolute configuration at the C-6 position of 15- 17 in reverse. The corrected Figure 3A is as follows and and the revised Supporting Information with the corrected structures for compounds 15-17 is included with this Correction.

Cobalt-Catalyzed Regioselective Olefin Isomerization under Kinetic Control

Olefin isomerization is a significant transformation in organic synthesis, which provides a convenient synthetic route for internal olefins and remote functionalization processes. The selectivity of an olefin isomerization process is often thermodynamically controlled. Thus, to achieve selectivity under kinetic control is very challenging. Herein, we report a novel cobalt-catalyzed regioselective olefin isomerization reaction. By taking the advantage of fine-tunable NNP-pincer ligand structures, this catalytic system features high kinetic control of regioselectivity. This mild catalytic system enables the isomerization of 1,1-disubstituted olefins bearing a wide range of functional groups in excellent yields and regioselectivity. The synthetic utility of this transformation was highlighted by the highly selective preparation of a key intermediate for the total synthesis of minfiensine. Moreover, a new strategy was developed to realize the selective monoisomerization of 1-alkenes to 2-alkenes dictated by installing substituents on the γ-position of the double bonds. Mechanistic studies supported that the in situ generated Co-H species underwent migratory insertion of double bond/β-H elimination sequence to afford the isomerization product. The less hindered olefin products were always preferred in this cobalt-catalyzed olefin isomerization due to an effective ligand control of the regioselectivity for the β-H elimination step.

Removal of the E-Olefin Barrier of Humulene Leading to Unnatural Terpenoid-like Skeletons

An unnatural terpenoid scaffold containing a bicyclo[5.4.0]undecane moiety, as well as a salvialane skeleton based on an intramolecular C-C bond formation strategy were synthesized. Such a strategy was made possible by the removal of strained E-olefin conformations of the humulene skeleton. Some compounds were identified to show PPARα antagonist activity.

Where is the Oxygen? Structural Analysis of α-Humulene Oxidation Products by the Crystalline Sponge Method

Crystal structures of α-humulene, a cyclic sesquiterpene, and its oxidized subproducts, were analyzed by the crystalline sponge method. Regio- and stereochemistry, including absolute configuration when a chiral oxidant was applied, and the stable conformations of all the scaffold-related compounds were successfully determined for samples on a 5-50 μg scale.