Catalytic C2 prenylation of unprotected indoles:Late‐stage diversification of peptides and two‐step total synthesis of tryprostatin B

C2 prenylated indoles are widespread in a variety of bioactive natural alkaloids.Therefore,theselective installation of prenyl group at C2 position of NH indoles is of great significance.However,the known protocols generally require a multi‐step procedure and stoichiometric promoters.Hereinwe develop a one‐step C2 prenylation of NH indole with cheap tert‐prenyl alcohol enabled by acidcatalysis.Salient features include good regioselectivity,step‐and atom‐economy,broad substratescope,and simple catalytic system.The mechanistic investigations demonstrate that both C2prenylation and C3 prenylation/migration pathways are engaged in the reaction.Notably,this practicalstrategy can be applied to the late‐stage diversification of tryptophan‐based peptides and concisesynthesis of tryprostatin B.

Protein prenylation and human diseases: a balance of protein farnesylation and geranylgeranylation

The protein prenylation is one of the essential post-translational protein modifications, which extensively exists in the eukaryocyte. It includes protein farnesylation and geranylgeranylation, using farnesyl pyrophosphate(FPP) or geranylgeranyl pyrophosphate(GGPP) as the substrate, respectively. The prenylation occurs by covalent addition of these two types of isoprenoids to cysteine residues at or near the carboxyl terminus of the proteins that possess Caa X motif, such as Ras small GTPase family. The attachment of hydrophobic prenyl groups can anchor the proteins to intracellular membranes and trigger downstream cell signaling pathway. Geranylgeranyl biphosphate synthase(GGPPS) catalyzes the synthesis of 20-carbon GGPP from 15-carbon FPP. The abnormal expression of this enzyme will affect the relative content of FPP and GGPP, and thus disrupts the balance between protein farnesylation and geranylgeranylation, which participates into various aspects of cellular physiology and pathology. In this paper, we mainly review the property of this important protein post-translational modification and research progress in its regulation of cigarette smoke induced pulmonary disease, adipocyte insulin sensitivity, the inflammation response of Sertoli cells, the hepatic lipogenesis and the cardiac hypertrophy.

Discovery of prenylated indole alkaloid and natural xanthone from cold-seep sediment derived fungus Talaromyces funiculosus SD-523

A new prenylated indole alkaloid 11,17-epi-mangrovamide A(1),a new natural occurring product,1,7-dihydroxy-6-methyl-8-hydroxymethyl-xanthone(2),two known alkaloids,mangrovamide A(3)and mangrovamide G(4),and four known polyketide derivatives(5–8)were isolated and identified from the cold-seep sediment derived fungal strain Talaromyces funiculosus SD-523.Their structures were elucidated by combination of nuclear magnetic resonance(NMR),high resolution electrospray ionization mass spectroscopy(HRESIMS),quantum chemical electronic circular dichroism(ECD),and DP4+probability analysis as well as by comparison of the data with literature reports.All isolated compounds were tested for antibacterial activities.

Do statins reduce hepatitis C RNA titers during routine clinical use?

AIM: To compare hepatitis C virus (HCV) titers in patients with chronic hepatitis C with and without exposure to 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins).METHODS: Medical records were reviewed for 6463 patients with documented HCV infection at a single center between March 2004 and September 2006. Patients with confi rmed viremia and meeting inclusion criteria were assigned to one of three groups: Group A (n = 50), dyslipidemic patients with statin usage during HCV RNA polymerase chain reaction (PCR) determination; Group B (n = 49), dyslipidemic patients with prior or future statin usage but not at the time of HCV RNA PCR determination; and Group C (n = 102), patients without statin usage during the study period. The primary analysis explored the effect of statin therapy on HCV viremia. Secondary analyses assessed class effect, dose response, and effect of other lipid-lowering therapies on HCV viral titers.RESULTS: Median HCV RNA titers did not signif icantly differ among the three groups (Group A: 4 550 000 IU/mL, Group B: 2 850 000 IU/mL, Group C: 3 055 000 IU/mL).For those subjects with longitudinal assessment of HCV viremia prior to and while on statins, there were no signif icant differences between pre- and post-HCV viral titers. Additionally, no differences in HCV titers were observed at any dose level of the most prescribed statin, simvastatin. However, hypertriglyceridemia independently correlated with HCV titers, and niacin exposure was associated with signif icantly lower viral titers (P < 0.05).CONCLUSION: There was no apparent effect of statins on HCV viral replication in this analysis. Further investigation is warranted to explore the possible antiviral properties of triglyceride-lowering agents and their potential role as adjuncts to standard HCV therapy.

Synthesis of Bioactive Natural Polymethoxyflavones and Their Vinyl Ether Derivatives

Bioactive natural polymethoxyflavones 1―6 and their vinyl ether derivatives 7―15 were synthesized by bromination,aromatic nucleophilic substitution,methylation,benzyl protection,Friedel-Crafts acetylation,aldol condensation,cyclization,DDQ dehydrogenation,regioselective demethylation,debenzylation and O-prenylation or O-farnesylation with resorcinol and appropriate substituted benzaldehydes as starting materials.Among them,compounds 7―15 are new compounds.Natural products 2―4 were firstly total synthesized.The syntheses of compounds 1,5 and 6 were efficiently improved by the new synthetic routes.The structures of all synthetic compounds were confirmed by NMR,IR spectra and MS.

Cloning and Characterization of Protein Prenyltransferase Alpha Subunit in Rice

Protein prenylation plays a crucial role in plant development and stress response.We report the function of pren yltra nsferase a-sub unit in rice.Protein-protei n in teractions showed that the fam esyl-transferase(OsPFT)/geranylgeranyltransferase-l(OsPGGT l-a)protein interacted together with OsPFT-P and OsPGGT l-p.The a-and p-subunits of OsPFT formed a heterodimer for the transfer of a farnesyl group from famesyl pyrophosphate to the CaaX-box-containing peptide N-dansyl-GCVLS.Furthermore,the tissue expressi on patter ns of the OsPFT and OsPGGT I sub units were similar,and these sub units were localized in the cytoplasm and nucleus.Moreover,OsPFT/OsPGGT/-a-deletion homozygous rice mutants had a lethal phenotype,and the heterozygous mutants exhibited reduced pollen viability.These results indicated that prenylation plays an important role in rice development.

Prenylated flavonoids from Tephrosia apollinea

In continuation of our chemical investigation on some medicinal plants of the genus Tephrosia, re-investigation of the methylenechloride/methanol （1：1） extract of the air-dried aerial part of Tephrosia apollinea afforded a new prenylated flavonoid 1, in addition to an aromatic ester, a sesquiterpene, a lignan and several known prenylated flavonoids. The structures were established by （^1H NMR, ^13C NMR, DEPT, ^1H-^1H COSY, HMQC, HMBC, NOESY and HRMS）. Relative configurations of 9 and 10 were confirmed by X-ray analysis.

ISOLATION, STRUCTURE ELUCIDATION AND SYNTHESIS OF A NEW PRENYLATED FLAVONOL, MAACKIAFLAVONOL, FROM MAACKIA TENUIFOLIA

A new prenylated flavonol, maackiaflavonol, was isolated from the ethanol extract of the roots of Maackia tenuifolia. Its structure was elucidated as 7-hydrox-8-prenylflavonol by means of spectroscopic analysis (UV, IR, MS, NMR and 1H-1H COSY) and confirmed by total synthesis.

Three new compounds from the leaves of Acanthopanax senticosus Harms

Three new compounds named (2E)prenyl benzoate-4-O-α-L-arabinopyranosyl (1→6) β-D-glucopyranoside (1), 7-methoxy-8-O-β-D-glucopyranosyl coumarin (2), and 3,4'-dihydroxy-3'-methoxy benzenepentanoic acid (3) were isolated from the leaves of Acanthopanax senticosus Harms. The structures of new compounds were determined by means of 2D NMR experiments and chemical methods.

A new prenylated arylbenzofuran derivative from Morus alba L.

2-[3,5-Di-O-β-D-glucosyl-4-(3-methylbut-2-enyl)phenyl]benzofuran-6-ol,a new prenylated arylbenzofuran derivative was isolated from Morus alba L.Its structure was elucidated by various spectroscopic methods including MS,~1H NMR,^(13)C NMR,DEPT,~1H-~1HCOSY,HMQC and HMBC.

Two New Dihydroflavanoids from Patrinia villosa Juss

Two new dihydroflavonoids were obtained from the traditional Chinese medicinal herb Patrinia villosa Juss. Their structures were elucidated as （2S）-5, 7, 2＇, 6＇-tetrahydroxy-6, 8-di （γ, γ-dimethylallyl） flavanone （1） and （2S）-5, 7, 2＇, 6＇-tetrahydroxy-6-1avandulylated flavanone （2） by spectroscopic methods including UV, IR, HR-TOF-MS, 1D NMR and 2D NMR techniques.

Pyrohyperforin, A New Prenylated Phloroglucinol from Hypericum perforatum

Pyrohyperforin, a new prenylated phloroglucinol was isolated from Hypericum perforatum, its structure was established on the basis of spectral data.

Prenylated Coumarins from Heracleum stenopterum,Peucedanum praeruptorum,Clausena lansium,and Murraya paniculata

Four hitherto unknown prenylated coumarins,namely 600-O-b-D-apiofuranosylapterin(1),40-O-isobutyroylpeguangxienin(2),6-(3-methyl-2-oxobutyroyl)-7-methoxycoumarin(3),and 6-hydroxycoumurrayin(4),were isolated from the ethanol extract of Heracleum stenopterum,Peucedanum praeruptorum,Clausena lansium,and Murraya paniculata,respectively.Their chemical structures were established on the basis of extensive spectroscopic analysis.Compound 2 exhibited in vitro cytotoxic activity against five human cancer cell lines(HL-60,A-549,SMMC-7721,MCF-7,and SW-480)with IC50 values ranging from 15.9 to 23.2μM.

Minor Prenylated Flavonoids from the Twigs of Macaranga adenantha and Their Cytotoxic Activity

Three new minor prenylated flavonoids,named macadenanthins A–C(1–3),together with three known ones(4–6),were isolated from the twigs of Macaranga adenantha.Their structures were elucidated on the basis of extensive spectroscopic analysis including NMR,UV and MS.The prenyl moieties in compounds 1–3 were further modified by cyclization and hydroxylation.The new compounds were tested for their cytotoxicity against four cancer cell lines(MCF-7,Hep G2,Hela and P388)and showed IC50 values in the range of 13.76–22.27 lM.

TWO NEM IS0PRENYL PLAVONOIDS FROM THE LEAVES OP GLYCYRRHIZA URALENSIS FISOH

Three flavonoids have been isolated from the leaves of Glycyrrhiza uralensis Fisch(licorice,Leguminosae).The structures have been identified as 5,7,3',4'-tetrahydroxy-3-methoxy-5'-isoprenyl flavone(I,uralenol-3-methylether),5,6,3',4'-tetrahydroxy-3-methoxy-6'-isoprenyl flavone (Ⅱ, unalene) and quercetin(Ⅲ).Ⅰ and Ⅱ are new compound.

New Prenylated flavonol from Hypericum japonicum

One new prenylated flavonol, 7,8-(2'',2'' -dimethylpyrano)-5,3',4'-trihydroxy-3-methoxyflavone was isolated from Hypericum japonicum. The chemical structure was determined by spectroscopic methods.

A new bioactive prenylated dihydroflavanoid from Dolichos tenuicaulis (Baker) Craib

A new prenylated dihydroflavonoid was obtained from the root of Dolichos tenuicaulis （Baker） Craib. The structure was elucidated as （2S）-5,2＇,6＇-trihydroxy-3＇″, 8-di （γ,γ-dimethyl-allyl）-2＇″, 2＇″-dimethylpyrano-[5＇″,6＇″： 6,7]-2＇″″,4＇″″-cyclohexadiene-1 ＇″″-one-[2＇″″,3＇″″： 3＇,4＇]-flavanone, named dolichnin A, by spectroscopic methods including UV, IR, HR-EI-MS, 1D NMR and 2D NMR techniques, and subsequently, the anticancer activity of this compound to inhibit human cancer cells＇ growth including A549, BEL-7402, Hep-3B, SMMC7721, HT-29, MCF-7, SGC-7902, K562, A498 and PC3 cell lines by MTT method was evaluated in vitro.

Flavonoid from the twigs and leaves of Erythrina variegata

In the present study,17 flavonoids,including 9 prenylated isoflavones,4 isoflavones,3 flavanones and 1 flavone,were isolated from the twigs and leaves of Erythrina variegata.By NMR spectroscopic means and comparision with the data in the leteratures,their structures were elucidated to be euchrenone b10(1),senegalensin(2),erythrinin C(3),scandenone(4),osajin(5),alpinum isoflavone(6),isoerysenegalensein E(7),erysenegalensein E(8),diprenylgenistein(9),abyssinone V(10),abyssinone V 4′-methyl ether(11),4′,7-dihydroxyflavanone(12),3′,5,7-trihydroxy-4′-methoxyisoflavone(13),2′,4′,5,7-tetrahydroxyisoflavone(14),genistein(15),daidzein(16),and apigenin(17).Except for compounds 1,4-7,and 9-10,other compounds were isolated from E.variegata for the first time.

Geranylated or prenylated flavonoids from Cajanus volubilis

Five new flavonoid derivatives,cajavolubones A-E(1-5),along with six known analogues(6-11)were isolated from Cajanus volubilis,and their structures were elucidated by spectroscopic analysis and quantum chemical calculations.Cajavolubones A and B(1 and 2)were identified as two geranylated chalcones.Cajavolubone C(3)was a prenylated flavone,while cajavolubones D and E(4 and 5)were two prenylated isoflavanones.Compounds 3,8,9 and 11 displayed cytotoxicity against HCT-116 cancer cell line.