Martin Banwell

• PhD, Hon.DSc
• Group Leader at Jinan University

Two epimeric pairs of N‐Ts‐protected cyclohexylamines that incorporate an unsaturated side‐chain at the C2 position have been prepared. Contrary to expectations, none of these underwent clean, photochemically‐induced intramolecular hydroamination reactions to give the corresponding perhydro‐indole or ‐quinoline. However, they did participate in eff...

Readily accessible, oxygenated 6,6‐dibromobicyclo[3.1.0]hexanes react with isovanillin in the presence of silver salts and an inorganic base to afford ring‐expanded/nucleophilic trapping products of various regio‐ and stereo‐chemical forms. Most such products undergo efficient, intramolecular Mizoroki‐Heck reactions to give the corresponding tetrah...

Biogenetically patterned total syntheses of the title alkaloids have been realised while a related synthesis of the racemic modification of the structure assigned to asperversiamide A suggests this is incorrect....

An efficient method for heteroarylation of unactivated, aliphatic C(sp3)−H bonds has been developed using a novel, visible light-promoted radical-relay sequence. The overall process likely occurs via hydrogen atom transfer between...

Diels–Alder cycloaddition reactions between the biomass-derived platform molecule levoglucosenone (2) and various cyclic dienes such as α-terpinene produced a range of adducts, including compound 28. Manipulation of these adducts then afforded a series of derivatives. So, for example, reductions of the associated carbonyl groups delivered the corre...

Heparanase (HPSE) is the only mammalian endo-β-glucuronidase known to catalyze the degradation of heparan sulfate. Dysfunction of HPSE activity has been linked to several disease states, resulting in HPSE becoming the target of numerous therapeutic programs, yet no drug has passed clinical trials to date. Pentosan polysulfate sodium (PPS) is a hete...

Sucrose esters have been deployed as surfactants in many food products since the 1950s. In addition to their useful physical characteristics, sucrose esters also have interesting biological properties that enhance their utility. This review critically examines the broad suite of biological activities that has been attributed to both synthetically-d...

Total syntheses of the title marine natural products have been achieved and so confirming the structures originally assigned to them. Upon subjecting agesasine A and its corresponding ethyl ester to Mitsunobu conditions, a 1,5‐cyclodehydration reaction takes place to give 2‐oxazolines. In contrast, on subjecting agesasine B to the same Mitsunobu co...

The synthesis of the enantiomer of the structure assigned to the title natural product has been achieved from abundant quinic acid. However, the NMR spectral data acquired on the synthetic material do not match those reported for ribisin F (which are of rather modest quality). In an effort to establish the true structure of ribisin F, an epimer of...

The structures assigned to all four members, 1‐4, of the recently reported favolasin class of natural product have been prepared for the first time by chemical synthesis. Thus, Suzuki‐Miyaura cross‐coupling chemistry was to establish the associated biaryl substructures The key step used in preparing the 1,5‐benzodioxepin ring system associated with...

A range of mono- and disaccharides, including glucose derivative 10, have been cleanly coupled, in the presence of a Pd catalyst, with various halogenated and structurally distinctive tropones, including "parent" compound 11, to afford the corresponding α- and β-anomeric forms of the tropolone glycosides, e.g., 12 and 13, respectively. Varying the...

Heparanase (HPSE) is the only mammalian endo-beta-glucuronidase known to catalyse the degradation of heparan sulfate. Dysfunction of HPSE activity has been linked to several disease states, resulting in HPSE becoming the target of numerous therapeutic programs, yet no drug has passed clinical trials to date. Pentosan polysulfate sodium (PPS) is a h...

Efficient and versatile syntheses of methylene-bridged bis-heterocycles that embody dihydroisoxazoline/pyridine or dihydroisoxazoline/quinoline pairings are described. These proceed under mild conditions and involve a visible light-mediated radical-relay sequence that begins with...

The Amaryllidaceae alkaloid (−)-galanthamine (1) is a reversible, competitive acetylcholinesterase inhibitor deployed clinically to treat the dementia associated with Alzheimer’s disease. Here, we describe a six-step synthesis of this natural product from simple, readily accessible starting materials. Enantioselective 1,2-reduction, Mitsunobu coupl...

A formal total synthesis of (-)-aspidophytine (2), a key substructure associated with the heterodimeric indole alkaloid haplophytine (1) and itself a natural product, has been established by employing the homochiral and enzymatically derived cis-1,2-dihydrocatechol 8 as a starting material. Specifically, compound 8 has been converted into the penta...

The readily prepared and vinylated β-carboline 11 has been converted over one or two steps into compounds 1-5, the structures assigned to the recently reported marine natural products orthoscuticellines A-E. The spectral data recorded on the synthetically derived compounds are fully consistent with the assigned structures and, on making allowances...

The morphinan alkaloids , especially codeine and morphine, are derived from the opium poppy and have been used for millennia for pain management. They remain vital medicines today, but climate change and geopolitical uncertainties threaten existing supply chains. In their Communication (e202203186), Martin G. Banwell, Ping Lan, and co‐workers detai...

Prostate cancer is the second most common malignancy in men and the development of effective therapeutic strategies remains challenging when more advanced, androgen‐independent or insensitive forms are involved. Accordingly, we have evaluated, using flow cytometry, confocal microscopy and image analysis, the anti‐proliferative effects of (+)‐2,3,9‐...

Two distinct and concise syntheses of zephycandidine A (1) from readily available starting materials are reported. In the first, the imidazole derived from piperonal (7 a) was subjected to reaction with o‐bromoiodobenzene or the corresponding di‐iodide in the presence of Pd[0] and thereby forming, via Buchwald–Hartwig and Heck reactions, a mixture...

From Lillies to Life‐Savers: Amaryllidaceae Alkaloid Inspired Coronavirus Inhibitors. The global COVID‐19 pandemic has claimed the lives of millions and disrupted nearly every aspect of human society. Currently, vaccines remain the only widely available medical means to address the cause of the pandemic, the SARS‐CoV‐2 virus. Unfortunately, current...

The global COVID‐19 pandemic has claimed the lives of millions and disrupted nearly every aspect of human society. Currently, vaccines remain the only widely available medical means to address the cause of the pandemic, the SARS‐CoV‐2 virus. Unfortunately, current scientific consensus deems the emergence of vaccine‐resistant SARS‐CoV‐2 variants hig...

The (±)‐, (+)‐ and (−)‐forms of 2‐amino‐3‐(8‐hydroxyquinolin‐3‐yl)‐propanoic acid (1 or 8HQ‐3Ala) have been prepared from o‐methoxyacetanilide (2). A combination of Vilsmeier‐Haack, Erlenmeyer‐Plöchl and methanolysis reactions was used to convert compound 2 into the Z‐configured dehydroamino acid derivative 5. Catalytic hydrogenation of the latter...

Certain sucrose mono-esters display excellent emulsifying properties as well as a range of other useful physicochemical characteristics that follow from their amphipathic nature. Accordingly, they are playing increasingly important roles in various food manufacturing industries. In this study, an homologous series of 6-O-acylsucrose mono-esters wit...

Certain cyclic sulfates (e.g. 23) together with various of their precursor sulfites (e.g. 21 and 22) have been prepared from the corresponding chiral, non-racemic bicyclo[2.2.2]octane-2,3-diols (e.g. 20). Such diols are obtained by engaging the corresponding enzymatically derived and enantiomerically enriched or homochiral cis-1,2-dihydrocatechol (...

An operationally simple synthesis of Z-configured and C3-unsubstituted N-sulfonyl-2-iminocoumarins (e.g., 8a) that proceeds under mild conditions is achieved by reacting 2-(1-hydroxyprop-2-yn-1-yl)phenols (e.g., 6a) with sulfonyl azides (e.g., 7a). The cascade process involved likely starts with a copper-catalyzed alkyne-azide cycloaddition (CuAAC)...

Although sulfated xylooligosaccharides are promising therapeutic leads for a multitude of afflictions, the structural complexity and heterogeneity of commercially deployed forms (e. g. Pentosan polysulfate 1) complicates their path to further clinical development. We describe herein the synthesis of the largest homogeneous persulfated xylooligomers...

The regio-isomeric alkynyl-substituted derivatives, 2 and 3, of the RNA Polymerase I (Pol I) transcription inhibitor CX-5461 (1) were prepared and the active one (compound 3) subjected to click reactions ([3 + 2]-cycloaddition reactions) with certain alkyl azides bearing biotin or fluorescent tags. Compounds 2 and 3, as well as four [3 + 2]-cycload...

The title alkaloids, often referred to collectively as crinines, are a prominent group of structurally distinct natural products with additional members being reported on a regular basis. As such, and because of their often notable biological properties, they have attracted attention as synthetic targets since the mid-1950s. Such efforts continue u...

The four most prominent forms of biomass are cellulose, hemicellulose, lignin and chitin. In efforts to develop sustainable sources of platform molecules there has been an increasing focus on examining how these biopolymers could be exploited as feedstocks that support the chemical supply chain, including in the production of fine chemicals. Many d...

Methods are reported for the efficient assembly of a series of phenol-derived propiolates, including the parent system 56, and their Au(I)-catalyzed cyclization (intramolecular hydroarylation) to give the corresponding coumarins (e.g., 1). Simple syntheses of natural products such as ayapin (144) and scoparone (145) have been realized by such means...

The tambjamines are a small group of bipyrrolic alkaloids that, collectively, display a significant range of biological activities including antitumor, antimicrobial and immunosuppressive properties. The key objective of the present study was to undertake preclinical assessments of tambjamine J (T‐J) so as to determine its in vivo antitumor effects...

cis-1,2-dihydrocatechols 5 (X= Me and Cl), which are available in homochiral form through the whole-cell biotransformation of toluene and chlorobenzene, respectively, undergo Diels-Alder cycloaddition reactions with certain electron-deficient dienophiles at 19 kbar (1.9 GPa). The favored products of such reactions are adducts of the general form 8...

Syntheses of a range of chemically well‐defined oligopyrrole/benzenoid hybrids are described using tandem Suzuki‐Miyaura cross‐coupling/bromo‐desilyation reaction sequences for linking borylated pyrroles, halogenated pyrroles and/or dibromobenzenes to one another. By such means, including iterative variants, a range of all α‐linked, all β‐linked ol...

In an ongoing study of the products formed on pyrolysis of chitin (4) under a range of conditions, we now detail the isolation and characterisation of the crystalline and hitherto undetected pyridine N-oxide 18 and enamide 19. Pathways for the formation of these products have been proposed and subjected to both experimental and computational assess...

The notable physical and chemical properties of sucrose fatty acid esters have prompted their use in the chemical industry, especially as surfactants, since 1939. Recently, their now well-recognized value as nutraceuticals and as additives in cosmetics has significantly increased demand for ready access to them. As such a review of current methods...

The development of functional as well as nutritional surfactants for the food industry remains a matter of great interest. In the present study, a series of 6ʹʹ-O-acylmaltotriose monoesters bearing alkyl side-chains of 10 to 18 carbons was prepared by enzymatic means. The emulsions derived from those monoesters incorporating palmitoyl, stearoyl, an...

The bioderived platform molecule levoglucosenone (LGO, 1) and its readily prepared pseudoenantiomer (iso-LGO, 2) have each been subjected to α-iodination reactions with the product halides then being engaged in palladium-catalyzed Ullmann cross-coupling reactions with various bromonitropyridines. The corresponding α-pyridinylated derivatives such a...

Synthetically-derived samples of (+)-(6aS,11aS)-2,3,9-trimethoxypterocarpan [(+)-1] and its enantiomer [(–)-1], both of which are examples of naturally-occurring isoflavonoids, were evaluated, together with the corresponding racemate, as cytotoxic agents against the HL-60, HCT-116, OVCAR-8 and SF-295 tumor cell lines. As a result it was established...

Pyrolysis of variously pre-treated or untreated samples of chitin (1) and certain congeners at 150-350 °C afforded a range of platform molecules, as exemplified by compounds 4, 5, 6, 8, 12 and 13. All of these products have been fully characterized, including by single-crystal X-ray analysis. Pathways for the formation of them are proposed and theo...

The title compounds, (–)-2 and (+)-2, representing potentially valuable building blocks for chemical synthesis, have each been prepared from cyclopentanone in eight steps. The pivotal one involves a resolution, through the quinine- or quinidine-promoted methanolysis of the cyclic anhydride (±)-10, leading to chromatographically separable pairs of e...

Chemoenzymatic methods for natural product synthesis: This review describes the use of certain microbially derived and enantiomerically pure cis‐1,2‐dihydrocatecols as starting materials in chemical synthesis. The application of these versatile metabolites to the assembly of a structurally diverse range of natural product frameworks is emphasized w...

While lignans and their biogenetic precursors can have various health benefits, the poor liposolubilities of such phenolic systems have restricted their application as antioxidants in the food industry. The research reported here was aimed at addressing these matters through derivatizing certain forms of such compounds and then assessing their prop...

Compounds 1-6 and 11 representing key members of the marinoquinoline family of natural products, together with the related marine alkaloid aplidiopsamine A (12), have been synthesized using various combinations of palladium-catalyzed Ullmann cross-coupling and reductive cyclization processes involving a C3-arylated pyrrole as the common intermediat...

The rare flavonoid isolaxifolin, a potent insecticide, has been touted as a potential grain-protecting agent. In order to assess any impact of this natural product on human health and to explore its various other biological properties, we have established a semisynthesis from the simpler but structurally related and more abundant natural product ap...

A mono‐oxide of the adduct derived from the [6+3] cycloaddition reaction between trimethylenemethane and 2‐methoxytropone undergoes an acid‐catalyzed rearrangement cascade to give, in a first step, a 3‐homoadamantyl carbocation that itself fragments to afford a poly‐substituted bicyclo[4.3.1]decane. This final product embodies key structural elemen...

Synthetically derived (Z)-ligustilide (1) has been subjected to photochemically-promoted dimerization processes under a range of conditions. By such means, varying distributions of the dimeric natural products tokinolides A-C (4, 3, and 6, respectively) and riligustilide (5) as well certain related (isomeric) compounds have been obtained. The struc...

Hypothesis: The development of functional and nutritional surfactants for the food industry remains a subject of great interest. Herein, therefore, we report on the design and synthesis of novel trisaccharide (raffinose) monoester-based surfactants in the expectation that they would display functional properties superior to certain disaccharide-ba...

On exposure to a combination of Cu[I]- and Pd[0]-based catalysts, compounds such as 1 and 7 engage in tandem Ullmann-Goldberg cross-coupling and cyclopalladation-reductive elimination reactions to give benzofurans such as 8. Related reactions involving hetero-Michael additions of o-halogenated phenols or anilines to propiolates and the Pd[0]-cataly...

The title bicyclic system 3, the adduct arising from the formal [6+3] cycloaddition of α‐tropolone O‐methyl ether (1) and trimethylenemethane (2), has been prepared and subject to single‐crystal X‐ray analysis. The chemical manipulation of adduct 3 in a range of ways is reported, including through acid‐catalysed rearrangement of the derived mono‐ox...

While the crystal structure analysis of the title compound, C26H38O15, a synthetic derivative of sucrose, was originally reported 40 years ago [Drew et al. (1979). Carbohydr. Res.71, 35–42], the present work has allowed for the determination of its absolute configuration through the application of resonant scattering techniques.

The C-1 substituted 6,6-dichlorobicyclo[3.1.0]hexanes 1a–c have been prepared and shown to undergo electrocyclic ring-opening to give the corresponding π-allyl cations 2 that cyclise to afford the spirocyclic products 3b–d, each of which has been subjected to single-crystal X-ray analysis.

The thermally-induced electrocyclic ring-opening of C2-symmetric (meso) 6,6-dibromobicyclo[3.1.0]hexanes such as 10 in the presence of the chiral, non-racemic 1°-amine 28 afforded a ca. 1:1 mixture of the diastereoisomeric and chromatographically separable 1-amino-2-bromo-2-cyclohexenes 37 (42%) and 38 (45%). Each of these was elaborated, over thir...

Hydrogenolytic cleavage of the ring-fused cyclopropane 11 using hydrogen in the presence of platinum oxide afforded the gem-dimethylated cyclohexane 12 in 99 % yield. In contrast, analogous treatment of congener 13 afforded only trace amounts of the targeted and gem-dimethylated sesquiterpene (+)-viridianol (1), the major products of reaction now b...

A total synthesis of compound 3 from p-bromophenol is reported and thereby establishing that this, rather than its cyclodehydrated counterpart 1 (as postulated originally), is the correct structure of the natural product myrsinoic acid F. The biological evaluation of compound 3 in a mouse-ear edema assay established that it is a significantly more...

Lactose fatty acid esters are high value-added derivatives of lactose and represent a class of biodegradable, nonionic, low molecular weight surfactants (emulsifiers) that have considerable potential in the food, cosmetic, and pharmaceutical industries. Certain lactose esters have also garnered attention for their biological activities. In this wor...

The structurally and stereoisomerically varied C7N aminocyclitol derivatives 2-4 have been prepared, using a versatile and flexible range of protocols, from the cis-1,2-dihydrocatechols 5 and 6, homochiral metabolites derived from the whole-cell biotransformation of the corresponding halobenzene. Reaction sequences that enable syntheses of the enan...

A total synthesis of the title sesquiterpene 4 is described that starts with the chiral, non-racemic cis-1,2-dihydrocatechol 10 obtained through the whole-cell biotransformation of p-iodotoluene. Compound 10 is elaborated over seven steps, including Negishi cross-coupling and intramolecular Diels-Alder (IMDA) cycloaddition reactions, to ketone 7 th...

The mechanism associated with the base-promoted conversion of alkoxy-substituted and ring-fused gem-dihalocyclopropanes such as 40 into annulated furans has been explored. Treatment of compound 40 with potassium tert-butoxide affords a mixture of furans 23/27 and 41, an outcome that suggests the intermediacy of the slowly interconverting oxonium yl...

Compounds such as 3, the product of a palladium[0]-catalyzed Ullmann cross-coupling of o-iodonitrobenzene and 2-iodocyclohex-2-en-1-one, undergo complementary modes of reductive cyclization depending upon the conditions employed. Thus, on treatment with hydrogen in the presence of palladium on carbon the tetrahydrocarbazole 4 is formed while reacti...

The enzymatically-derived and enantiomerically pure (1S,2S)-3-bromocyclohexa-3,5-diene-1,2-diol (7) has been elaborated over 10 steps into cyclohexenone 8. The latter compound embodies the enantiomeric form of the C-ring associated with the hexacyclic framework of the alkaloid aspidophytine (2). As such, this work sets the stage for effecting the c...

Emulsifiers derived from renewable resources such as sucrose and fatty acids are high volume commodity chemicals and currently produced by traditional chemical synthesis techniques that lack the capacity to form the most desirable mono-esters (of sucrose) in a selective and efficient fashion. The development of new emulsifiers (surfactants) from al...

Cross-coupling reactions, especially those that are catalyzed by palladium, have revolutionized the way in which carbon–carbon bonds can be formed. The most commonly deployed variants of such processes are the Suzuki–Miyaura, Mizoroki–Heck, Stille, and Negishi cross-coupling reactions, and these normally involve the linking of an organohalide or ps...

A range of structural variations on the tricarbocyclic core 2 of the anti-bacterial agent platencin 1, including those represented by compounds 14, 15, and 27, have been prepared and certain of these elaborated, through substrate-controlled enolate alkylation reactions, to analogues of the natural product. Preliminary biological evaluation of these...

The synthesis of the structure, 1, assigned to the anti-inflammatory natural product myrsinoic acid F is reported together with a means for preparing its Z-isomer 21. While neither of these compounds corresponds to the natural product, both of them are anti-inflammatory agents (as determined using a mouse ear edema assay) with congener 1 being nota...

(±)-Crinane embodies the tetracyclic framework associated with some of the most common Amaryllidaceae alkaloids. It has now been prepared in ten steps from 6,6-dibromobicyclo[3.1.0]hexane (2). The initial step involves the thermally-induced electrocyclic ring opening of cyclopropane 3 and capture of the resulting π-allyl cation with benzylamine to...

The palladium-catalyzed Ullmann cross-coupling of β-iodoenones and β-iodoacrylates such as 5 (X = I) with o-halonitroarenes and o-iodobenzonitriles including 2 affords products such as compound 7. These can be engaged in a range of reductive cyclization reactions leading to heterocyclic frameworks such as 3,4-benzomorphan derivative 43.

Sugar fatty acid esters are non-ionic surfactants that are widely exploited in the food and cosmetics industries, as well as in the oral care and medical supply fields. Accordingly, new methods for their selective synthesis and the “tuning” of their emulsifying properties are of considerable interest. Herein we report simple and irreversible enzyma...

Aminocyclitol 2, a recently isolated and notable antifungal agent, was prepared from homochiral γ-hydroxycyclohexenone 4, which is itself available in six steps from l-(+)-tartaric acid (3). The well-defined rigidifying effect arising from the 1,2-diacetal protecting group associated with compound 4 and its derivatives allows for high levels of reg...

The title compounds of the general form 1 can be produced at large scale and in essentially enantiomerically pure form (when X≠H) through the whole cell biotransformation of the corresponding aromatic. The “dense” and varied functionality associated with these metabolites mean that they have become increasingly useful chirons for the total synthesi...

A total synthesis of the marine alkaloid discoipyrrole C (3) is described. In the pivotal step, the 2,3,5-trisubstituted pyrrole 19 was treated with MoOPH in the presence of MeOH, and the resulting methoxylated 1,2-dihydro-3H-pyrrol-3-one 20 subjected to reaction with potassium carbonate in MeOH then trifluoroacetic acid and H2O. This gave a mixtur...

Stereoselective total syntheses of the four stereoisomeric forms of guaiacylglycerol 8-O-4′-coniferyl ether, viz., compounds 1, ent-1, 2, and ent-2, have been established. The key step involves an Evans/Seebach auxiliary-controlled and syn-selective aldol process followed, in the reaction sequences leading to the anti-compounds, by a Mitsunobu reac...

A series of O- and N-linked 1,6-enynes (e.g. 11) has been prepared and each subjected to a palladium-catalyzed intramolecular Alder-ene (IMAE) reaction and thus producing the isomeric and cyclic 1,4-diene (e.g. 12). These processes proceed most effectively when a triethylsilyl group is attached to the alkyne moiety and so generating alkenylsilanes...

A total synthesis of the diastereoisomeric pair of compounds, 4, assigned to the marine alkaloid discoipyrrole D is reported. A series of palladium-catalysed cross-coupling and other reactions was employed to assemble the relevant 1,2,3,4-tetra-substituted pyrrole (16) that was engaged in MoOPH-mediated oxidative cyclization then conjugate addition...

A total synthesis of compound 3 from d-(−)-tartaric acid is reported, thereby establishing that the structure, including relative stereochemistry, originally assigned to the cyclic carbonate-containing natural product aspergillusol B is correct.