Novel sesquiterpene esters with alkaloid and monoterpene and related compounds from Tripterygium hypoglaucum: A new class of potent anti-HIV agents

Duan, Hong‐Quan; Takaishi, Yoshihisa; Bando, Mai; Kido, Masaru; Imakura, Yasuo; Lee, Kuo Hsiung̀

doi:10.1016/s0040-4039(99)00339-1

Cited by 56 publications

(50 citation statements)

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“…The small coupling constant of J1,2 = 3.6 Hz between H-1 and H-2 indicated that the H-2 was equatorial. These data revealed that the relative configuration of the dihydro-β-agarofuran sesquiterpene core in 1 was identical to that of triptonine A [10] and the related compounds [12,27,28]. The relative configurations of the groups at two macrocyclic rings were determined by comparison of the NMR spectroscopic data with those of triptonine A [10], which was established by X-ray crystallography.…”

Section: Resultsmentioning

confidence: 86%

“…These characteristic NMR data suggested 1 to be a dimacrolide sesquiterpene pyridine alkaloid [5][6][7][8][9][10][11][12]. The 1 H-and 13 C-NMR data (Table 1) of 1 were similar to those of triptonine A [10], previously isolated from T. hypoglaucum, except for the following two differences: one difference was the different chemical shifts of C-5″, C-6″, C-7″ and C-8″ in 1 from those in triptonine A due to the presence of a furan group in the second macrocyclic ring system in 1. The 2-(3′-carboxybutyl)-3-furanoic acid unit was disclosed from 1 H-1 H COSY correlations of H3-10″/H1-2″/H2-3″/H2-4″ and H-7″/H-8″, and the key HMBC correlations from H-3″ and H-10 ″ to C-1″, from H-4″ to C-6″, from H-7″ to C-5″, C-6″, C-8″ and C-9″, and from H-8″ to C-5″, C-6″ and C-7″ ( Figure 2A).…”

Section: Resultsmentioning

confidence: 99%

“…So far, only seven dimacrolide sesquiterpene pyridine alkaloids [5][6][7][8][9][10][11][12] have been isolated from plants. Compounds 1 and 2 represent the first example of dimacrolide sesquiterpene pyridine alkaloids bearing an extra furan ring in their second macrocyclic ring system.…”

Section: Resultsmentioning

confidence: 99%

“…They were characterized by a polyhydroxylated dihydroagarofuran core and two dicarboxylic acid derivatives linked via four ester bonds forming two macrocyclic systems. DMSPAs are a rare class of compounds naturally occurring in a limited number of plants, such as cathedulin E3 [5][6][7][8], cathedulin E4 [5][6][7][8], cathedulin-K19 [9], and cathedulin-K20 [9] from Catha edulis (Forsk), triptonine A [10,11] and triptonine B [10,11] from Tripterygium hypoglaucum, and tripterygiumine A [12] from Tripterygium wilfordii. Moreover, triptonine B has been reported to inhibit HIV replication with EC50 value <0.10 μg/mL in H9 lymphocytes with a significant therapeutic index (TI) value (TI > 1000) [11].…”

Section: Introductionmentioning

confidence: 99%

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Dimacrolide Sesquiterpene Pyridine Alkaloids from the Stems of <em>Tripterygium regelii</em>

Fan

Zhu

et al. 2016

Preprint

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Abstract:Two new dimacrolide sesquiterpene pyridine alkaloids (DMSPAs), dimacroregelines A (1) and B (2), were isolated from the stems of Tripterygium regelii. The structures of both compounds were characterized by extensive 1D and 2D NMR spectroscopic analyses, as well as HRESIMS data. Compounds 1 and 2 are two rare DMSPAs possessing unique 2-(3′-carboxybutyl)-3-furanoic acid units forming the second macrocyclic ring, representing the first example of DMSPAs bearing an extra furan ring in their second macrocyclic ring system. Compound 2 showed inhibitory effects on the proliferation of human rheumatoid arthritis synovial fibroblast cell (MH7A) at a concentration of 20 μM.

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Section: Resultsmentioning

confidence: 86%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Dimacrolide Sesquiterpene Pyridine Alkaloids from the Stems of <em>Tripterygium regelii</em>

Fan

Zhu

et al. 2016

Preprint

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“…There is still considerable enthusiasm for minnelide (Arora et al, 2015), a prodrug derivative of triptolide, which is currently undergoing phase I clinical trials as a treatment for advanced gastrointestinal tumors in the United States (clinicaltrials.gov identifier NCT01927965). Other metabolites with encouraging preclinical performance are the appetite-reducing triterpenoid quinone celastrol (Liu et al, 2015) and the immunosuppressive sesquiterpene pyridine alkaloid wilfordine (and naturally occurring structural analogs; Duan et al, 1999).…”

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confidence: 99%

Integrative Approaches for the Identification and Localization of Specialized Metabolites in Tripterygium Roots

et al. 2016

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ORCID IDs: 0000-0001-6565-9584 (B.M.L.); 0000-0001-7934-7987 (N.S.); 0000-0002-0600-6847 (D.Š.).Members of the genus Tripterygium are known to contain an astonishing diversity of specialized metabolites. The lack of authentic standards has been an impediment to the rapid identification of such metabolites in extracts. We employed an approach that involves the searching of multiple, complementary chromatographic and spectroscopic data sets against the Spektraris database to speed up the metabolite identification process. Mass spectrometry-based imaging indicated a differential localization of triterpenoids to the periderm and sesquiterpene alkaloids to the cortex layer of Tripterygium roots. We further provide evidence that triterpenoids are accumulated to high levels in cells that contain suberized cell walls, which might indicate a mechanism for storage. To our knowledge, our data provide first insights into the cell type specificity of metabolite accumulation in Tripterygium and set the stage for furthering our understanding of the biological implications of specialized metabolites in this genus.

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Enantioselective Desymmetrization ofmeso-Decalin Diallylic Alcohols by a New Zr-Based Sharpless AE Process: A Novel Approach to the Asymmetric Synthesis of PolyhydroxylatedCelastraceae Sesquiterpene Cores

Spivey¹,

Woodhead²,

Weston³

et al. 2001

Angew. Chem.

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Crude plant extracts of the Celastraceae have been valued since antiquity for their stimulant, appetite suppressive, antiarthritic, antibacterial, insect repellent, and memoryrestorative properties. [1] Pervasive among the secondary metabolites isolated from this class of plants is a large family of polyhydroxylated sesquiterpene esters having a dihydro-bagarofuran skeleton. [2] Many members of this family, partic-ularly esters of three polyhydroxylated agarofurans: euonyminol, 4b-hydroxyalatol, and 14-deoxyalatol, exhibit significant biological activity. These include: triptogelins A-1/A-6 [3a] and celhin A [3b] (antitumor), wilfortrine [4] (immunosuppressive), wilforine [5] (insecticidal), and celangulin [6a] and cathedulins E-3/E-4/E-5 [6b] (insect antifeedant). Additionally, hypoglaunine B and related macrocyclic lactone derivatives of euonyminol have recently been shown to display significant anti-HIV activity [7] (Scheme 1). A B RO RO OR OR OR OH RO RO OR OR OR OH O HO HO OH OH X 1 O OH H X 2 X 4 X 3 AcO AcO OAc O AcO O OAc H O OH O N O OH O O O euonyminol: X 1 ,X 2 ,X 3 ,X 4 = OH 4β-hydroxyalatol: X 1 ,X 3 = OH, X 2 ,X 4 = H 14-deoxyalatol: X 1 ,X 2 ,X 3 ,X 4 = H epoxidative enantioselective desymmetrization hypoglaunine B 4 14 Scheme 1. Desymmetrization strategy. R protecting group, Ac acetyl.One striking feature of the three core structures common to these natural products is a symmetric array of hydroxyl groups on the top face of their ªnorthernº periphery. We were intrigued by the possibility of exploiting this symmetry to facilitate their synthesis. In particular, we identified epoxide B as a pivotal intermediate for the preparation of all the core structures and we envisaged that a two-directional synthesis of meso-diallylic alcohol A followed by epoxidative enantioselective desymmetrization [8] would provide an efficient route to this intermediate (Scheme 1). Here we describe how the successful implementation of this plan required the development of a Zr-based Sharpless asymmetric epoxidation (AE) process for tertiary diallylic alcohols.At the outset of our work, only one trans-decalinic diallylic alcohol had been reported. [9] In view of this limited precedent, and the potentially labile nature of the structure, we opted to evaluate the feasibility of our strategy on simple model system 5 (Scheme 2). Epoxide 1 was prepared from naphthalene by Birch reduction (Na/NH 3 ; 74 % yield) then epoxidation (CH 3 CO 3 H; 87 % yield). [10] Ring opening with Et 2 AlCN, [11] followed by completely diastereoselective epoxidation and trans-diaxial ring opening with Me 3 Al gave triol 4. Selective mesylation then anti elimination in neat DBU furnished the requisite diallylic alcohol 5. This alcohol was prone to partial [1,3]-allylic rearrangement to give the corresponding conjugated dienyl alcohol on silica, but could be obtained pure after chromatography on grade 1 basic alumina.Sharpless AE [12] with either catalytic [13] or stoichiometric [13] amounts of Ti(OiPr) 4 /d-(À)-diisopropyl tartrate (DIPT) pro-...

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Novel sesquiterpene esters with alkaloid and monoterpene and related compounds from Tripterygium hypoglaucum: A new class of potent anti-HIV agents

Cited by 56 publications

References 7 publications

Dimacrolide Sesquiterpene Pyridine Alkaloids from the Stems of <em>Tripterygium regelii</em>

Dimacrolide Sesquiterpene Pyridine Alkaloids from the Stems of <em>Tripterygium regelii</em>

Integrative Approaches for the Identification and Localization of Specialized Metabolites in Tripterygium Roots

Enantioselective Desymmetrization ofmeso-Decalin Diallylic Alcohols by a New Zr-Based Sharpless AE Process: A Novel Approach to the Asymmetric Synthesis of PolyhydroxylatedCelastraceae Sesquiterpene Cores

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