Synthesis of marchantin C, a novel microtubule inhibitor from liverworts

Recently, remarkable microtubule inhibitor and anti-tumor activities of the bisbibenzyl marchantin C—isolated from liverworts like Marchantia polymorpha since 1983—were found. In this Letter we describe the first and efficient total synthesis of this subtype of bisbibenzylic compounds with two biarylether connections. The structure was confirmed by the spectroscopic data which were analyzed carefully to exclude any errors in arene connection and substitution pattern.     

Antifungal variant bis(bibenzyl)s from the liverwort Asterella angusta

Bioassay-guided fractionation of the diethyl ether extract of the liverwort Asterella angusta led to the isolation of two antifungal bis(bibenzyl)s,riccardin I(1),and angustatin A(2).Their structures were established by spectroscopic analysis(1D NMR and 2D NMR,IR,MS).Compound 1 is a novel variant riccardin-type bis(bibenzyl),while compound 2 is the first nonheteratom-containing variant bis(bibenzyl)possessing a bibenzyl-phenanthrene skeleton.     

Difunctional heterocycles: A convenient one pot synthesis of novel bis(benzoxazoles) from bis(o-aminophenols)

New bis(benzoxazoles) 14 and 17 have been synthesized in excellent yields from the corresponding bis(o-aminophenols) by refluxing with triethyl orthoformate. 6,6′-Bis(benzoxazole) ( 14 ) has also been prepared utilizing Gold's reagent. Compound 14 is inert to Reissert reaction conditions. However, the Reissert reaction on 5,5′-bis(benzoxazole) (17) led to ring opened product 20 .     

Two new cyclic bis(bibenzyl)s,isoriccardinquinone A and B from the liverwort Marchantia paleacea

From the 95% ethanol extract of the Hong Kong liverwort, Marchantiapaleacea, guided by bioactivity directed isolation, two novel isoriccardinquinones A and B were obtained together with previously known marchantin C, isoriccardin C and phenanthrene derivative, 2-hydroxy-3,7-dimethoxyphenanthrene. The structures of the new compounds were established by high field spectroscopic methods, including 2D NMR techniques.     

Total synthesis of a cytotoxic acetogenin,pyranicin

[structure: see text] The first total synthesis of a new cytotoxic acetogenin, pyranicin (1), is described. SmI(2)-induced reductive cyclization of beta-alkoxy acrylate 4 proceeded stereoselectively to give 16,20-syn-19,20-trans-THP derivative 14, which was efficiently transformed into the 19,20-cis-THP derivative 18 through Mitsunobu lactonization. Wittig reaction of the phosphonium salt 2 obtained therefrom with butenolide 3 at -78 degrees C followed by reduction and deprotection afforded 1 in good overall yield.     

A novel synthesis of metallogermacyclopropane and molybdenum bis(iminophosphorano)carbene complexes from bisgermavinylidene

The reaction of bisgermavinylidene [(Me3SiN=PPh2)2C=Ge-->Ge=C(PPh2=NSiMe3)2] (1) with M(CO)5(THF) ( M = Cr, W, Mo) afforded the metallagermacyclopropane [(Me-3SiN=PPh2)2CGeM(CO)3[M(CO)5]] [M = W (2), Cr (3), Mo (4)]; in one of the reactions, compound 4 reacts further to give a "pincer" carbene complex [(CO)3Mo[C(Ph2P=NSi Me3)2]] (5); the X-ray structures of compounds 2 and 5 have been determined.     

Novel Bis(bibenzyl) and (Propylphenyl)bibenzyl Derivatives from Dendrobium nobile

Two novel compounds possessing a bis(bibenzyl) (see 1 ) and a (propylphenyl)bibenzyl skeleton (see 2 ) and eight known compounds were isolated from the stems of Dendrobium nobile Lindl . (Orchidaceae). Their structures were identified by spectroscopic analyses.     

A new (propylphenyl)bibenzyl from Eria bambusifolia

A new (propylphenyl)bibenzyl, bambusifolol (1), along with six known compounds, batatasin III (2), tristin (3), 3-hydroxy-5-methoxy bibenzyl (4), gigantol (5), 3′,5-dimethoxy-9,9′-diacetyl-4,7′-epoxy-3,8′-bilign-7-ene-4′-methol (6) and balanophonin (7) were isolated from the whole plants of Eria bambusifolia. Their structures were elucidated by the means of extensive spectroscopic analysis. 3–7 were isolated from the genus Eria for the first time and 2 obtained originally from E. bambusifolia. All the compounds isolated were evaluated for their cytotoxicity against human tumour HL-60, SMMC-7721, A-549, MCF-7 and SW-480 cell lines, but none showed significant activity.     

Total synthesis of cytotoxic anhydrophytosphingosine pachastrissamine (jaspine B)

Starting from L-serine, a stereoselective synthesis of pachastrissamine, a structurally novel anhydrosphingosine derivative, is reported in this Letter. [structure: see text]     

Total synthesis of (-)-microcarpalide, a novel microfilament disrupting metabolite

The stereoselective total synthesis of (-)-microcarpalide, a recently discovered 10-membered lactone of fungal origin displaying a remarkable disrupting action on actin microfilaments, was accomplished by using ring-closing metathesis (RCM) as the key step for the formation of the medium-sized ring. The diene ester required for the macrocyclization reaction was assembled via DCC-mediated esterification of two suitable partners, each bearing a terminal alkene group. The alcohol fragment was synthesized from n-bromohexane through a seven-step sequence entailing two consecutive stereoselective homologations of chiral boronic esters as strategic transformations for the sequential insertion of the two stereocentres with the final S absolute configuration, using (+)-pinanediol as the chiral director; final elaboration to the desired C(11) framework envisaged treatment with an allyl Grignard reagent and oxidative cleavage of the boronic scaffold. In contrast, the acidic fragment was prepared in ten steps from d-tartaric acid, whose C(4) backbone was elongated to the required C(7) skeleton by means of two distinct Swern-Wittig oxidation-homologation sequences.     

Total synthesis of the cytotoxic cyclopeptide mollamide, isolated from the sea squirt Didemnum molle

Full details of a total synthesis of the novel reverse prenyl substituted cyclic peptide mollamide, isolated from the ascidian Didemnum molle, are described.     

A new (propylphenyl)bibenzyl derivative from Dendrobium williamsonii

A new (propylphenyl)bibenzyl derivative, dendrowillol A (1), along with 22 known compounds were isolated from the whole plants of Dendrobium williamsonii. Their structures were elucidated by means of extensive spectroscopic analysis. Cytotoxicity evaluation against five human tumour lines showed that all the compounds tested displayed very weak cytotoxicity when compared with the positive control taxol, but selective inhibitory effects on HL-60 for several compounds tested were observed, with IC₅₀ values ranging from 4.48 to 11.04 μM.     

Total synthesis and stereochemical reassignment of (+)-dolastatin 19, a cytotoxic marine macrolide isolated from Dolabella auricularia

Using conformational analysis and biogenetic considerations, a revised configurational assignment for the cytotoxic marine macrolide dolastatin 19 is proposed, together with its validation by completion of the first total synthesis. Key features of the highly stereocontrolled route include an asymmetric vinylogous Mukaiyama aldol reaction to simultaneously install both the remote C13 stereocenter and the C10-C11 (E)-trisubstituted olefin, two sequential 1,4-syn boron-mediated aldol reactions, and a late-stage, α-selective Mukaiyama glycosylation to append the l-rhamnose-derived pyranoside.     

Total synthesis of (-)-ulapualide A, a novel tris-oxazole macrolide from marine nudibranchs, based on some biosynthesis speculation

A new, second generation, total synthesis of ulapualide A (1), whose stereochemistry was recently determined from X-ray analysis of its complex with the protein actin, is described. The synthesis is designed and based on some speculation of the biosynthetic origin of the contiguous tris-oxazole unit in ulapualide A, alongside that of the related co-metabolites that contain only two oxazole rings, e.g. 6 and 7. The mono-oxazole carboxylic acid 67b and the mono-oxazole secondary 55b alcohol which, together, contain all of the 10 asymmetric centres in the natural metabolite, were first elaborated using a combination of contemporary asymmetric synthesis protocols. Esterification of 67b with 55b under Yamaguchi conditions gave the ester 77 which was then converted into the omega-amino acid 18a following simultaneous deprotection of the t-butyl ester and the N-Boc protecting groups. Macrolactamisation of 18a, using HATU, now gave the key intermediate macrolactam 17, containing two of the three oxazole rings in ulapualide A (1). A number of procedures were used to introduce the third oxazole ring in ulapualide A from 17, including: a) cyclodehydration to the oxazoline 78a followed by oxidation using nickel peroxide leading to 76; b) dehydration to the enamide 79, followed by conversion into the methoxyoxazoline 78b, via 80, and elimination of methanol from 78b using camphorsulfonic acid. The tris-oxazole macrolide 76 was next converted into the aldehyde 82b in four straightforward steps, which was then reacted with N-methylformamide, leading to the E-alkenylformamide 83. Removal of the TBDPS protection at C3 in 83 finally gave (-)-ulapualide A, whose 1H and 13C NMR spectroscopic data were indistinguishable from those obtained for naturally derived material. It is likely that the tris-oxazole unit in ulapualide A (1) is derived in nature from a cascade of cyclodehydrations from an acylated tris-serine precursor, e.g.9, followed by oxidation of the resulting tris-oxazoline intermediate, i.e.10. It is also plausible to speculate that the biosynthesis of metabolites related to ulapualide A, e.g. the bis-oxazole 6 and the imide 7, involve cyclisations of just two of the serine units in 9. These speculations were given some credence by carrying out pertinent interconversions involving the bis-oxazole amide 24, the enamide 25, the imide 26, the oxazoline 27 and the tris-oxazole 30 as model compounds. An alternative strategy to the tris-oxazole macrolide intermediate 76 was also examined, involving preliminary synthesis of the aldehyde 73, containing a shortened (C25-C34) side chain from 67b and 47b. A Wadsworth-Emmons olefination reaction between 73 and the phosphonate ester 74 led smoothly to the E-alkene 75, but we were not able to reduce selectively the conjugated enone group in 75 to 76 without simultaneous reduction of the oxazole alkene bond, using a variety of reagents and reaction conditions.     

Synthesis,characterization and cytotoxic investigations of novel bis(indole) analogues besides antimicrobial study

Two series of novel bis(indole) analogues viz., N′-((5-substituted-1H-indol-3-yl)methylene)-n-(1H-indol-3-yl)alkanehydrazides (7a–f) and N′-((5-substituted-1-(3-methylbut-2-enyl)-1H-indol-3-yl)methylene)-n-(1H-indol-3-yl)acetohydrazide (8a–f) were synthesized and characterized by spectral analysis. The target molecules were screened for their antimicrobial, anticancer activities and structure and activity relationship (SAR) was investigated. Compounds 7a, 7c and 8a were found to be active in antimicrobial screening. Anticancer screening reveals that Compound 7c was active against HeLa cell line with an IC₅₀ of 43.1 μM and compound 7d was found to be interesting candidate with an IC₅₀ of 26.0 and 30.2 μM against Colo-205 and Hep G2 cell lines respectively.     

Total synthesis of the cytotoxic alkaloid luotonin A

The structure of luotonin A was unambiguously confirmed by total synthesis. Deprotonation of 3-oxo-1H-pyrrolo[3,4-b]quinoline gave an anion which was coupled with 2-sulfinylaminobenzoyl chloride (prepared by reaction of anthranilic acid with thiolyl chloride) to afford the natural product in 85 % yield.     

Total synthesis of (±)-dicranenones,novel cyclopentenonyl fatty acids

Dicranenones 1 and 2 have been synthesized from the intermediate 12, which was either derived from methyl jasmonate 7 or prepared by the intramolecular ring formation of diazo compound 14.     

The synthesis of novel aliphatic bis(acenaphthelene) reactive monomers

Novel aliphatic‐bridged bis(acenaphthalene)s are synthesized and evaluated as potential precursors to high‐temperature reactive monomers. It was found that as the length of the aliphatic bridging unit increased, the thermal stability of bis(acenaphthalene) increased and melting point decreased. The use of an alternative route for the introduction of the reactive vinyl group resulted in a dramatic increase in monomer purity. The increase in monomer purity resulted in the creation of a processing window that enabled samples to be melt cast prior to polymerization, greatly improving their suitability as high‐temperature polymers. Polymerized samples were found to have high thermal stability, indicating they have potential as high temperature materials. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43:5072–5082, 2005