ORCID Profile
0000-0002-7297-1303
Current Organisation
University of Melbourne
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Organic Chemistry | Natural Products Chemistry | Organic Chemical Synthesis | Organic Chemical Synthesis | Biological And Medical Chemistry | Biologically Active Molecules | Structural Chemistry | Macromolecular and Materials Chemistry | Synthesis of Materials | Analytical Spectrometry | Characterisation Of Macromolecules | Physical Chemistry (Incl. Structural) | Sociology and Social Studies of Science and Technology
ANZSRC Socio-Economic Objective (SEO)
Chemical sciences | Expanding Knowledge in the Chemical Sciences | Treatments (e.g. chemicals, antibiotics) | Human Pharmaceutical Treatments (e.g. Antibiotics) | Workforce Transition and Employment | Organic Industrial Chemicals (excl. Resins, Rubber and Plastics) | Cancer and Related Disorders |
Related Links
Publications
Studies toward the pharmacophore of salvinorin A, a potent κ opioid receptor agonist
Publisher: American Chemical Society (ACS)
Date: 29-12-2005
DOI: 10.1021/JM049438Q
Total Synthesis of 8-Deshydroxyajudazol B
Publisher: American Chemical Society (ACS)
Date: 16-03-2011
DOI: 10.1021/OL200331U
Abstract: The total synthesis of a stereoisomer of 8-deshydroxyajudazol B (4), the putative biosynthetic intermediate of the ajudazols A (1) and B (2), is described. The key steps in the synthesis included an intramolecular Diels-Alder (IMDA) reaction to secure the isochromanone fragment, a novel selective acylation/O,N-shift to give a hydroxyamide which was cyclized to the oxazole and a high yielding Sonogashira coupling to form the C18-C19 bond. Partial alkyne reduction then afforded the target 4.
Formal Total Synthesis of (+)-Citrafungin A
Publisher: CSIRO Publishing
Date: 2009
DOI: 10.1071/CH09182
Abstract: The formal total synthesis of the fungal GGTase I inhibitor (+)-citrafungin A 1 is described. The key steps include a selective vinyl anion addition of the anion derived from iodide 10 to the lactone 9 and lactonization/selective deprotection of the allylic alcohols 8 and 23 to afford the citrafungin lactone. Esterification with the isocitrate 6 afforded citrafungin A tetra-t-butyl ester 5 which completed the formal total synthesis.
Hetero-Diels–Alder synthesis of the spiroketal fragment of reveromycin A
Publisher: Elsevier BV
Date: 10-2000
Biomimetic synthesis of the novel 1,4-dioxanyloxy fragment of silvestrol and episilvestrol
Publisher: Elsevier BV
Date: 2005
The hetero-Diels–Alder approach to spiroketals
Publisher: Royal Society of Chemistry (RSC)
Date: 2009
DOI: 10.1039/B819966N
Abstract: The hetero-Diels-Alder reaction can provide spiroketal systems with excellent stereoselectivity. This perspective article will briefly outline the scope and limitations of this approach for the production of naturally occurring spiroketals and derivatives.
Enantiospecific Synthesis of the Phospholipase A2 Inhibitor (−)-Cinatrin B
Publisher: American Chemical Society (ACS)
Date: 23-01-2002
DOI: 10.1021/JO016221K
Abstract: The first enantiospecific synthesis of phospholipase A2 (PLA2) inhibitor (-)-cinatrin B (2) from the D-arabinose derivative 9 is described. The spirolactone system was formed by an Ireland-Claisen rearrangement of the allyl ester 8 followed by hydrolysis and stereoselective iodolactonization. The stereoselectivity of the rearrangement was controlled by the asymmetry in the allylic alcohol fragment. Ester (S)-8 gave the desired rearrangement product 7 and the epimer 13 in high yield as a 73:27 ratio, respectively. The final stereocenter at C2 was introduced via a chelation-controlled addition of the Grignard reagent derived from trimethylsilylacetylene to alpha-hydroxy ketone 6. Transformation of the terminal alkyne into the methyl ester 21 followed by acetal hydrolysis and selective lactol oxidation afforded cinatrin B methyl ester (22). Base hydrolysis and acid-induced relactonization then gave (-)-cinatrin B (2).
Total Synthesis of Viridiofungins A and B
Publisher: American Chemical Society (ACS)
Date: 22-04-2021
Resolvin D2 supports MCF-7 cell proliferation via activation of estrogen receptor
Publisher: American Society for Pharmacology & Experimental Therapeutics (ASPET)
Date: 30-07-2014
Abstract: Inflammation has been implicated in tumor initiation, angiogenesis, and metastasis, and linked to the development of more aggressive, therapy-resistant estrogen receptor (ER)-positive breast cancer. Resolvin D2 (RvD2) is a potent anti-inflammatory lipid mediator. As RvD2 may be synthesized within breast tumors by both tumor cells and the surrounding stroma cells and is present in plasma at bioactive concentrations, we sought to characterize the impact of RvD2 on cell processes underlying breast tumor growth and spread. Trypan-blue exclusion, transfection with estrogen response element (ERE) reporter, real-time quantitative polymerase chain reaction, competitive radioligand binding assays, Western blotting, and immunofluorescence were the techniques used. Unexpectedly, whereas RvD2 (10-1000 nM) supported the proliferation of the ER-positive breast tumor (MCF-7) cells, it did not affect the ER-negative MDA-MB-231 cell number. The proliferative effect of RvD2 in MCF-7 cells was attenuated by the ER antagonist ICI 182,780 (7α-[9-[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17β-diol). Furthermore, RvD2 increased ERE transcriptional activity in a number of ER-positive breast and ovarian tumor cell lines. This activation was also inhibited by ICI 182,780. RvD2 altered the expression of a subset of estrogen-responsive genes. Although binding experiments showed that RvD2 did not directly compete with [(3)H]17β-estradiol for ER binding, prior exposure of MCF-7 cells to RvD2 resulted in a significant reduction in the apparent cytosolic ER density. Confocal immunocytochemistry and Western blotting studies showed that RvD2 promoted nuclear localization of ERα. These observations indicate that RvD2 displays significant but indirect estrogenic properties and has the potential to play a role in estrogen-dependent breast cancer progression.
Synthesis of Alkyl Citrates (−)-CJ-13,981, (−)-CJ-13,982, and (−)-L-731,120 via a Cyclobutene Diester
Publisher: American Chemical Society (ACS)
Date: 28-06-2018
DOI: 10.1021/ACS.ORGLETT.8B01665
Abstract: An efficient and step-economic new approach to alkyl citrate natural products from a cyclobutene diester is presented. The key sequence involves a formal [2 + 2]-cycloaddition of a silylketene acetal with dimethylacetylene dicarboxylate to provide the cyclobutene diester 14 with 4.5:1 stereoselectivity. Exposure of diester 14 in acidic methanol effected a hydrolysis, intramolecular oxy-Michael reaction, and cyclobutanone methanolysis cascade to give the triester 15. Iodination and elimination then afforded a key alkyl citrate alkene intermediate, which was converted into the natural products (-)-CJ-13,982 (1), (-)-CJ-13,981 (2), and (-)-L-731,120 (3) via a cross-metathesis and subsequent reduction.
Total Synthesis of (–)-Episilvestrol and (–)-Silvestrol
Publisher: Wiley
Date: 04-10-2007
Frontispiece: The Nargenicin Family of Oxa‐Bridged Macrolide Antibiotics
Publisher: Wiley
Date: 02-03-2020
An unprecedented stereoselective base-induced trimerization of an α-bromovinylsulfone
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7OB01121K
Abstract: A unprecedented base-induced trimerization of bromovinylsulfone 1 afforded the cyclohexene 6 as a single diastereoisomer.
A cis-β-iron(iii ) SALPN catalyst for hydrogen atom transfer reductions and olefin cross couplings
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D3OB01085F
Abstract: An inexpensive Fe( iii ) SALPN catalyst for MHAT reactions such as reductions of α,β-unsaturated carbonyl compounds and olefin cross couplings is reported.
Synthetic studies on the salicylihalamides: macrolactone formation via ring closing metathesis versus macrolactonization
Publisher: Elsevier BV
Date: 10-2000
Synthesis of the C9–C29 fragments of ajudazols A and B
Publisher: Elsevier BV
Date: 08-2007
Total Synthesis of (−)-Reveromycin B
Publisher: American Chemical Society (ACS)
Date: 23-12-1999
DOI: 10.1021/OL991281M
Abstract: [structure: see text] The total synthesis of the epidermal growth factor inhibitor reveromycin B (2) is described. A novel, convergent, and stereoselective reaction sequence was utilized to construct the 5,6-spiroketal system 10 which was converted into the natural product 2 by a 16-step sequence.
Chemistry and Biology of Acyloin Natural Products
Publisher: Georg Thieme Verlag KG
Date: 27-12-2022
DOI: 10.1055/A-2004-1228
Abstract: This review details the isolation, biosynthesis, biological activity, and synthesis of α-hydroxy ketone (acyloin) natural products. The role of these compounds as biosynthetic precursors to complex natural products and synthetic strategies to access the sensitive acyloin moiety and stereochemistry are highlighted. 1 Introduction 1.1 Xenocyloins 1.2 Biological Activity 1.3 Biosynthesis 1.4 Acyloins as Discoipyrrole Biosynthetic Precursors 2 Total Synthesis of Acyloin Natural Products 2.1 Kurasoins A and B 2.2 Soraphinol A and Circumcin B 2.3 4-Hydroxysattabacin and Actinopolymorphol A 2.4 Actinopolymorphol B 2.5 Sattazolins and Sattabacins 2.6 Catalyst Development and Application in Acyloin Synthesis 2.7 Xenocyloins 3 Conclusion
Towards the Synthesis of Dihydrooxepino[4,3-b]pyrrole-Containing Natural Products via Cope Rearrangement of Vinyl Pyrrole Epoxides
Publisher: American Chemical Society (ACS)
Date: 02-12-2015
DOI: 10.1021/ACS.ORGLETT.5B02965
Abstract: An approach to the dihydrooxepino[4,3-b]pyrrole core of diketopiperazine natural products which utilizes a vinyl pyrrole epoxide Cope rearrangement was investigated. It was found that an ester substituent on the epoxide was essential for the [3,3]-rearrangement to occur. Density functional calculations with M06-2X provided explanations for the effects of the pyrrole and ester groups on these rearrangements.
Synthetic approaches to the alkaloids of the ancistrocladaceae: control of the diastereoisomer excess in the synthesis of axially chiral biaryls: a synthesis of (–)-ancistrocladinine
Publisher: Royal Society of Chemistry (RSC)
Date: 1991
DOI: 10.1039/C39910000278
The Mitochondrial Apoptotic Effectors BAX/BAK Activate Caspase-3 and -7 to Trigger NLRP3 Inflammasome and Caspase-8 Driven IL-1β Activation
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.CELREP.2018.10.103
Abstract: Intrinsic apoptosis resulting from BAX/BAK-mediated mitochondrial membrane damage is regarded as immunologically silent. We show here that in macrophages, BAX/BAK activation results in inhibitor of apoptosis (IAP) protein degradation to promote caspase-8-mediated activation of IL-1β. Furthermore, BAX/BAK signaling induces a parallel pathway to NLRP3 inflammasome-mediated caspase-1-dependent IL-1β maturation that requires potassium efflux. Remarkably, following BAX/BAK activation, the apoptotic executioner caspases, caspase-3 and -7, act upstream of both caspase-8 and NLRP3-induced IL-1β maturation and secretion. Conversely, the pyroptotic cell death effectors gasdermin D and gasdermin E are not essential for BAX/BAK-induced IL-1β release. These findings highlight that innate immune cells undergoing BAX/BAK-mediated apoptosis have the capacity to generate pro-inflammatory signals and provide an explanation as to why IL-1β activation is often associated with cellular stress, such as during chemotherapy.
Total Synthesis of (+)-Crocacin D
Publisher: American Chemical Society (ACS)
Date: 22-01-2002
DOI: 10.1021/OL017092X
Abstract: [structure: see text] The first asymmetric synthesis of (+)-crocacin D (4) is described. The key steps in the sequence are the stereoselective assembly of the stereotetrad via a substrate-controlled aldol reaction and anti-selective reduction, formation of the (E,E)-diene by a Stille cross-coupling between the stannane 8 and vinyl iodide 9, and the acylation of (Z)-enecarbamate 6 with the acid chloride derived from polyketide fragment 16 which introduced the (Z)-enamide functionality.
Total synthesis of naphthylisoquinoline alkaloids
Publisher: Elsevier
Date: 1997
Synthesis of Homochiral CoIII– and MnIV–[2.2]Paracyclophane Schiff Base Complexes with Predetermined Chirality at the Metal Centre
Publisher: Wiley
Date: 14-07-2016
Synthetic studies towards the squalestatins and zaragozic acids
Publisher: Elsevier BV
Date: 1994
An effectivecis-β-octahedral Mn(iii ) SALPN catalyst for the Mukaiyama–Isayama hydration of α,β-unsaturated esters
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9CC03921J
Abstract: Two cis -β-Mn III SALPN catalysts were synthesised and tested in the Mukaiyama – Isayama hydration of α,β-unsaturated esters.
Synthesis of myxobacteria metabolites
Publisher: Walter de Gruyter GmbH
Date: 27-04-2012
Abstract: Myxobacteria are an excellent source of novel secondary metabolites with a range of biological activities. This review details the synthesis of several ex les of these natural products. The total synthesis of all the members of the crocacin family is presented where the stereochemistry of the stereotetrad was set via a tin-mediated syn -aldol reaction followed by selective anti -reduction. The other key step in the route to crocacins A, B, and D was the introduction of the enamide functionality by acylation of an enecarbamate. A formal synthesis of apicularen A is also discussed, which involved a base-induced macrolactonization reaction and a transannular oxy-Michael cyclization to secure the tetrahydropyran ring. Finally, the total synthesis of deshydroxyajudazol B is summarized. This route details a modified approach to the 2,4-disubstituted oxazole, and a Diels–Alder reaction followed by aromatization was utilized to form the isochromanone moiety. A highly efficient Sonogashira coupling followed by partial reduction then gave deshydroxyajudazol B.
Biosynthesis and Ether‐Bridge Formation in Nargenicin Macrolides
Publisher: Wiley
Date: 11-02-2019
Total Synthesis of the Proposed Structure of 8-Deshydroxyajudazol A: A Modified Approach to 2,4-Disubstituted Oxazoles
Publisher: American Chemical Society (ACS)
Date: 14-11-2012
DOI: 10.1021/JO302055W
Abstract: The total synthesis of the proposed structure for the minor myxobacterial metabolite 8-deshydroxyajudazol A (3) is described. The isochromanone moiety present in the eastern fragment was constructed by an intramolecular-Diels-Alder (IMDA). Difficulties were encountered with the formation of the 2,4-disubstituted oxazole, so this was synthesized via a modified approach. This involved selective acylation of the diol 7 with acid 8, azide displacement of the secondary alcohol, and subsequent azide reduction in the presence of base which induced an O,N shift to give the hydroxyamide 23. Cyclodehydration then gave the desired oxazole 24 and deprotection followed by mesylation and elimination produced the C15 alkene 5. Sonogashira coupling with the eastern fragment vinyl iodide 6 and partial reduction yielded 8-deshydroxyajudazol A (3).
Total Synthesis of the Epidermal Growth Factor Inhibitor (−)-Reveromycin B
Publisher: American Chemical Society (ACS)
Date: 03-03-2001
DOI: 10.1021/JO001646C
Abstract: The total synthesis of the epidermal growth factor inhibitor reveromycin B (2) in 25 linear steps from chiral methylene pyran 13 is described. The key steps involved an inverse electron demand hetero-Diels-Alder reaction between dienophile 13 and diene 12 to construct the 6,6-spiroketal 11 which upon oxidation with dimethyldioxirane and acid catalyzed rearrangement gave the 5,6-spiroketal aldehyde 9. Lithium acetylide addition followed by oxidation/reduction and protective group manipulation provided the reveromycin B spiroketal core 8 which was converted into the reveromycin A (1) derivative 6 in order to confirm the stereochemistry of the spiroketal segment. Introduction of the C1-C10 side chain began with sequential Wittig reactions to form the C8-C9 and C7-C6 bonds, and a tin mediated asymmetric aldol reaction installed the C4 and C5 stereocenters. The final key steps to the target molecule 2 involved a Stille coupling to introduce the C21-C22 bond, succinoylation, selective deprotection, oxidation, and Wittig condensation to form the final C2-C3 bond. Deprotection was effected by TBAF in DMF to afford reveromycin B (2) in 72% yield.
Total synthesis of alkyl citrate natural products
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C3OB42231C
Abstract: This review highlights the synthesis of members of the alkyl citrate family of natural products. The focus is on the stereoselective construction of the alkyl citrate moiety common to these compounds.
Stereoselective Total Synthesis of (−)‐Spirofungin A by Utilising Hydrogen‐Bond Controlled Spiroketalisation
Publisher: Wiley
Date: 10-12-2010
Abstract: The stereoselective total synthesis of the spiroketal containing Streptomyces metabolite (-)-spirofungin A (1) is described. A key step involved a spiroketalisation controlled by an intramolecular H-bond which favoured the desired spiroketal 4 (13:1 ratio). The presence of the intramolecular H-bond in 4 is possibly due to a 1,5-alkyne-oxygen interaction. Other key steps include an efficient cross-metathesis to form the spiroketal precursor, a tin mediated syn-aldol reaction and a Stille cross-coupling reaction to create the C22C23 bond. A final Wittig extension followed by deprotection gave (-)-spirofungin A (1).
Divinatorins A-C, new neoclerodane diterpenoids from the controlled sage Salvia divinorum
Publisher: American Chemical Society (ACS)
Date: 20-08-2003
DOI: 10.1021/NP030313I
Abstract: Three new neoclerodane diterpenoids, inatorins A-C (7-9), have been isolated from the leaves of Salvia inorum. The compounds were identified by spectroscopic methods as derivatives of the antibiotic (-)-hardwickiic acid (10), which was also isolated, along with four other known terpenoids. Neither the crude extract nor 7-9 displayed antimicrobial activity.
Total Synthesis of the Proposed Structure for Spirofungin B: A Reassignment of the Stereochemistry
Publisher: American Chemical Society (ACS)
Date: 21-02-2004
DOI: 10.1021/OL049873E
Abstract: [structure: see text] The total synthesis of the proposed structure for spirofungin B (2) is described. The data for the synthetic material did not compare with that for the natural product leading to the conclusion that the structure 2 assigned for spirofungin B is incorrect. Analysis of the NMR data reported for spirofungins A and B as well as related spiroketals allowed for the reassignment of the stereochemistry of spirofungin B to be that corresponding to 15-epi-spirofungin A (27).
Characterisation of nickel(II) extraction by 2-hydroxy-5-nonylacetophenone oxime (LIX 84) in a micellar phase
Publisher: Elsevier BV
Date: 10-2003
Formal Synthesis of (-)-O-Methylancistrocladine
Publisher: American Chemical Society (ACS)
Date: 09-1995
DOI: 10.1021/JO00122A067
Formal Total Synthesis of (+)‐Zaragozic Acid C through an Ireland–Claisen Rearrangement
Publisher: Wiley
Date: 19-09-2006
Total synthesis of (+)-rottnestol†
Publisher: Royal Society of Chemistry (RSC)
Date: 1999
DOI: 10.1039/A904379I
The Wittig Reaction of 2-t-Butoxycarbonyl-1-methoxycarbonylethylidenetriphenylphosphorane: A Surrogate for the Stobbe Reaction
Publisher: CSIRO Publishing
Date: 1987
DOI: 10.1071/CH9871737
Abstract: The reaction of 2-t-butoxycarbonyl-l-methoxycarbonylethylidenetriphenylphosphorane (3) with a range of aromatic aldehydes has been explored. The resultant itaconic esters, obtained in high yield, are readily converted into methyl 4-acetoxynaphthalene-2-carboxylates.
The Nargenicin Family of Oxa‐Bridged Macrolide Antibiotics
Publisher: Wiley
Date: 16-12-2020
Abstract: The nargenicin family of antibiotic macrolides comprise a group of bacterial natural products with a rare ether bridged cis ‐decalin moiety and a narrow spectrum of activity. Most family members were identified almost four decades ago and were placed on the shelf due to the numbers of broad‐spectrum compounds available at the time. However, in light of rising rates of antimicrobial resistance, there has been a renewed interest in the use of narrow‐spectrum antimicrobials. Here, we review the history of this family of compounds, including synthetic approaches, and highlight the recently uncovered genetic basis for nargenicin production. Given the renewed pharmaceutical interest in these compounds, we also investigate structure–activity relationships among these molecules, with a view to the future development of members of this unusual antibiotic family.
Synthesis of Biotinylated Episilvestrol: Highly Selective Targeting of the Translation Factors eIF4AI/II
Publisher: American Chemical Society (ACS)
Date: 05-03-2013
DOI: 10.1021/OL400401D
Abstract: Silvestrol (1) and episilvestrol (2) are protein synthesis inhibitors, and the former has shown efficacy in multiple mouse models of cancer however, the selectivity of these potent cytotoxic natural products has not been described. Herein, it is demonstrated that eukaryotic initiation factors eIF4AI/II were the only proteins detected to bind silvestrol (1) and biotinylated episilvestrol (9) by affinity purification. Our study demonstrates the remarkable selectivity of these promising chemotherapeutics.
Synthesis of the core of apicularen A by transannular conjugate addition
Publisher: Elsevier BV
Date: 11-2002
Mulberry Diels−Alder Adducts: Synthesis of Chalcomoracin and Mulberrofuran C Methyl Ethers
Publisher: American Chemical Society (ACS)
Date: 02-03-2010
DOI: 10.1021/OL9026705
Abstract: The synthesis of each of the heptamethyl ethers of the mulberry Diels-Alder adducts chalcomoracin (1) and mulberrofuran J (2) is described. The key steps in each approach involved a biomimetic intermolecular [4+2]-cycloaddition between a dehydroprenylphenol diene derived from an isoprenoid-substituted phenolic compound and an alpha,beta-unsaturated alkene of a chalcone as the dienophile. Critical to the success of the Diels-Alder reaction was the presence of the free phenol in the 2'-hydroxychalcone.
Total Synthesis and Stereochemical Reassignment of Citrafungin A
Publisher: American Chemical Society (ACS)
Date: 14-11-2019
DOI: 10.1021/ACS.ORGLETT.9B03830
Abstract: The stereoselective 12-step total synthesis of the reassigned structure for citrafungin A (
Chemistry and biology of spiroacetals from myxobacteria
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1OB00026H
Abstract: This review details the isolation, biosynthesis, biological activity and synthesis of spiroacetals from the myxobacterium Sorangium cellulosum .
Enantiospecific synthesis of the phospholipase A2inhibitors (−)-cinatrin C1and (+)-cinatrin C3
Publisher: Royal Society of Chemistry (RSC)
Date: 2003
DOI: 10.1039/B308028E
Abstract: The enantiospecific synthesis of (-)cinatrin C1 (3) and (+)-cinatrin C3 (5) from the D-arabinose derivative 9 is described. The stereochemistry at C2 was introduced via a chelation-controlled addition of a carbanion to alpha-hydroxy ketone 8. The best selectivity was achieved by use of the Grignard reagent derived from trimethylsilylacetylene. Transformation of the terminal alkyne into methyl ester 17 followed by acetal hydrolysis and selective lactol oxidation gave cinatrin C1 dimethyl ester (7). Base hydrolysis and acid induced relactonization then gave a 1:1 mixture of cinatrins C1 (3) and C3 (5).
Synthesis of isochromanone containing natural products from myxobacteria
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D2OB01926D
Abstract: This review details the biological activity, biosynthesis and synthesis of isochromanone metabolites isolated from myxobacteria.
Formal Total Synthesis of (−)-Apicularen A via Transannular Conjugate Addition
Publisher: American Chemical Society (ACS)
Date: 19-03-2004
DOI: 10.1021/OL0497943
Abstract: The formal total synthesis of the myxobacteria metabolite (-)-apicularen A (1) is described. The key step involved a novel acid-mediated transannular conjugate addition of the C13 hydroxyl into the alpha,beta-unsaturated ketone in either of the macrolactones 5a or 5b to provide the same trans-pyranone 4. Conversion of 4 into the known apicularen intermediate diol 3 completed the formal synthesis. [reaction: see text]
Enantiospecific total synthesis of the squalene synthase inhibitors (-)-CJ-13,982 and its enantiomer from a common intermediate
Publisher: Springer Science and Business Media LLC
Date: 25-10-2018
DOI: 10.1038/JA.2017.127
Abstract: The total syntheses of both the natural and unnatural enantiomers of the alkyl citrate natural product CJ-13,982 (1) from the common d-ribose-derived acid 6 are described.
Synthetic approaches to the naphthyl-isoquinoline alkaloids. Part 2. The total synthesis of (–)-O-methylancistrocladine and (+)-O-methylhamatine and their enantiomers
Publisher: Royal Society of Chemistry (RSC)
Date: 1991
DOI: 10.1039/P19910000845
A Synthetic Approach to (+)-Dioncophylline C
Publisher: CSIRO Publishing
Date: 1995
DOI: 10.1071/CH9952013
Abstract: In a synthetic approach to (+)-dioncophylline C (1), a coupling between the chiral oxazoline (3) and the Grignard reagent obtained from bromide (4) gave the major biaryl (5) and the minor biaryl (12) in good yield and high diastereoselectivity (yield 70% ratio 91:9). The stereochemistry of the major biaryl (5) was confirmed by X-ray structure analysis of the derived crystalline iodide salt (13).
Synthetic Studies toward the Reveromycins: Asymmetric Synthesis of the Spiroketal Segment of Reveromycin B
Publisher: American Chemical Society (ACS)
Date: 03-1997
DOI: 10.1021/JO962316O
Biosynthesis and Ether-Bridge Formation in Nargenicin Macrolides
Publisher: Wiley
Date: 11-02-2019
Abstract: The nargenicin family of antibiotics are macrolides containing a rare ether-bridged cis-decalin motif. Several of these compounds are highly active against multi-drug resistant organisms. Despite the identification of the first members of this family almost 40 years ago, the genetic basis for the production of these molecules and the enzyme responsible for formation of the oxa bridge, remain unknown. Here, the 85 kb nargenicin biosynthetic gene cluster was identified from a human pathogenic Nocardia arthritidis isolate and this locus is solely responsible for nargenicin production. Further investigation of this locus revealed a putative iron-α-ketoglutarate-dependent dioxygenase, which was found to be responsible for the formation of the ether bridge from the newly identified deoxygenated precursor, 8,13-deoxynargenicin. Uncovering the nargenicin biosynthetic locus provides a molecular basis for the rational bioengineering of these interesting antibiotic macrolides.
Total synthesis of (+)-crocacin C
Publisher: Elsevier BV
Date: 2001
Synthetic approaches to the naphthyl-isoquinoline alkaloids. Part 1. Dehydroancistrocladisine
Publisher: Royal Society of Chemistry (RSC)
Date: 1991
DOI: 10.1039/P19910000841
Enantiospecific Synthesis of the Heparanase Inhibitor (+)-Trachyspic Acid and Stereoisomers from a Common Precursor
Publisher: Royal Society of Chemistry (RSC)
Date: 2007
DOI: 10.1039/B708594J
Abstract: The total synthesis of natural (+)-trachyspic acid and its enantiomer is described starting from a common 2-deoxy-d-ribose derivative. The synthesis of the corresponding C3 epimers from the same starting material is also described. Each stereoisomer was assayed for heparanase inhibition.
Formal Total Synthesis of Spirangien A
Publisher: American Chemical Society (ACS)
Date: 15-01-2013
DOI: 10.1021/OL3033253
Abstract: A formal total synthesis of the spiroketal containing cytotoxic myxobacteria metabolite spirangien A (1) is described. The approach utilizes a late introduction of the C20 alcohol that mirrors the biosynthesis of this compound. The key steps involved a high yielding cross metathesis reaction between enone 6 and alkene 7 to give E-enone 4 and a Mn-catalyzed conjugate reduction α-oxidation reaction to introduce the C20 hydroxyl group. Acid treatment of the α-hydroxyketone 4 gave spiroketal 19 which was converted into known spirangien A (1) advanced intermediate spiroketal 3.
Total synthesis of the endogenous inflammation resolving lipid resolvin D2 using a common lynchpin
Publisher: Beilstein Institut
Date: 03-12-2013
DOI: 10.3762/BJOC.9.310
Abstract: The total synthesis of the endogenous inflammation resolving eicosanoid resolvin D2 ( 1 ) is described. The key steps involved a Wittig reaction between aldehyde 5 and the ylide derived from phosphonium salt 6 to give enyne 17 and condensation of the same ylide with aldehyde 7 to afford enyne 11 . Desilylation of 11 followed by hydrozirconation and iodination gave the vinyl iodide 4 and Sonogashira coupling between this compound and enyne 3 provided alkyne 18 . Acetonide deprotection, partial reduction and ester hydrolysis then gave resolvin D2 ( 1 ).
Synthetic studies towards the mulberry Diels–Alder adducts: H-bond accelerated cycloadditions of chalcones
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2OB25115A
Abstract: The methyl ether derivatives 2, 4 and 6 of the mulberry Diels-Alder adducts chalcomoracin (1) and mulberrofuran C (3) and kuwanon J (5) respectively have been synthesized by a thermal [4 + 2]-cycloaddition reaction between a chalcone and dehydroprenyl diene. A H-bonded ortho OH substituent on the chalcone was found to be essential for Diels-Alder reactivity. Density functional theory calculations show that the OH group lowers the barrier for the Diels-Alder reaction by 2-3 kcal mol(-1) compared with OMe. The acceleration by the OH group is traced to two transition-state effects: a stronger diene-chalcone interaction and better planarity of the aryl-diene unit.
A four step synthesis of violaceic acid
Publisher: Elsevier BV
Date: 03-2018
Enantiospecific synthesis of (–)-trachyspic acid
Publisher: Royal Society of Chemistry (RSC)
Date: 2005
DOI: 10.1039/B504258E
Abstract: The enantiospecific synthesis of (-)-trachyspic acid () is presented. This has allowed for the assignment of the absolute configuration of natural (+)-trachyspic acid as 3S,4S,6S.
Synthesis and biological evaluation of a potent salicylihalamide A lactam analogue
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2OB26649K
Abstract: The first synthesis of a lactam analogue of salicylihalamide A (1) is reported. A key step in the approach was a photochemical acylation coupling between amine 10 and dioxinone 9 to form the amide 19. Acetylation followed by RCM with Grubbs 1st generation catalyst gave the desired E-lactam 23 (E : Z ratio 87 : 13) as the major compound. Conversion of macrolactam 23 into the vinyl iodide 26 followed by Cu catalysed cross coupling with the diene amide 7 gave aza-salicylihalamide analogue 3 in good yield. This compound demonstrated potent activity against several human leukaemia cell lines.
Macrolactam analogues of macrolide natural products
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6OB02149B
Abstract: The chemical modification of macrolide natural products into aza- or lactam analogues is a strategy employed to improve their metabolic stability and biological activity.
Synthetic approaches to the alkaloids of the ancistrocladaceae: (–)-O-methylancistrocladine and (+)-O-methylhamatine
Publisher: Royal Society of Chemistry (RSC)
Date: 1990
DOI: 10.1039/C39900000894
The Synthesis of Stypandrol, a Toxic Binaphthalenetetrol Isolated From Stypandra imbricata : New Syntheses of Dianellidin and Stypandrone
Publisher: CSIRO Publishing
Date: 1988
DOI: 10.1071/CH9881087
Abstract: New syntheses of the naphthalenoid natural products dianellidin [1- (1,8-dihydroxy-3-methylnaphthalen-2-yl) ethanone ] (2) and stypandrone [6-acetyl-5-hydroxy-7-methylnaphthalenel-1,4-dione] (20), which rely on the Fries rearrangement, are described. This methodology is then applied to the synthesis of stypandrol [1,1′-(1,1′,8,8′-tetrahydroxy- 6,6′-dimethyl-2,2′-binaphthalene-7,7′-diyl) bisethanone ] (1), a toxic naphthalenetetrol isolated from Stypandra imbricata R.Br. ('blind grass').
Total Synthesis of the Potent Anticancer Aglaia Metabolites (−)-Silvestrol and (−)-Episilvestrol and the Active Analogue (−)-4′-Desmethoxyepisilvestrol
Publisher: American Chemical Society (ACS)
Date: 13-01-2009
DOI: 10.1021/JA808402E
Abstract: Total synthesis of the anticancer 1,4-dioxane containing natural products silvestrol (1) and episilvestrol (2) is described by an approach based on the proposed biosynthesis of these novel compounds. The key steps included an oxidative rearrangement of the protected d-glucose derivative 11 to afford the 1,4-dioxane 12, which could be elaborated to the coupling partner 5 and a photochemical [3 + 2]-cycloadditon between the 3-hydroxyflavone 27 and methyl cinnamate followed by base-induced alpha-ketol rearrangement and reduction to give the cyclopentabenzofuran core 33. The core (-)-6 and 1,4-dioxane fragment 5 were united by a highly stereoselective Mitsunobu coupling with the modified azodicarboxylate DMEAD to afford the axial coupled product 36. Deprotection then gave episilvestrol (2). Silvestrol (1) was synthesized by a coupling between core (-)-6 and the dioxane 44 followed by deprotection. Compound 1 was also synthesized from episilvestrol (2) by a Mitsunobu inversion. In addition, the analogue 4'-desmethoxyepisilvestrol (46) was synthesized via the same route. It was found that 46 and episilvestrol 2 displayed an unexpected concentration-dependent chemical shift variation for the nonexchangeable dioxane protons. Synthetic compounds 1, 2, 38, 46, and 54 were tested against cancer cells lines, and it was found that the stereochemistry of the core was critical for activity. Synthetic analogue 4'-desmethoxyepisilvestrol (46) was also active against lung and colon cancer cell lines.
Salvinorins D-F, new neoclerodane diterpenoids from Salvia divinorum, and an improved method for the isolation of salvinorin A
Publisher: American Chemical Society (ACS)
Date: 18-04-2003
DOI: 10.1021/NP0205699
Abstract: Three new neoclerodane diterpenoids, salvinorins D-F (4-6), have been isolated from the leaves of Salvia inorum. The structures were elucidated by chemical and spectroscopic methods, particularly 1D and 2D NMR. A simplified isolation method using chromatography on activated carbon also gave improved yields of the controlled substance salvinorin A (1) and of salvinorin C (3).
Total Synthesis of 2‴,5‴-Diepisilvestrol and Its C1‴ Epimer: Key Structure Activity Relationships at C1‴ and C2‴
Publisher: American Chemical Society (ACS)
Date: 20-07-2012
DOI: 10.1021/NP300376F
Abstract: The first total synthesis of the low-abundance natural product 2''',5'''-diepisilvestrol (4) is described. The key step involved a Mitsunobu coupling between cyclopenta[b]benzofuran phenol 7 and dioxane lactol 6. Deprotection then gave a 1:2.6 ratio of natural product 2''',5'''-diepisilvestrol (4) and its C1 epimer 1''',2''',5'''-triepisilvestrol (15) in 50% overall yield. An in vitro protein translation inhibition assay showed that 2''',5'''-diepisilvestrol (4) was considerably less active than episilvestrol (2), while the unnatural isomer 1''',2''',5'''-triepisilvestrol (15) was essentially inactive, showing that the configuration at C1''' and C2''' has a large effect on the biological activity.
Autoxidation of salvinorin A under basic conditions
Publisher: American Chemical Society (ACS)
Date: 11-2005
DOI: 10.1021/JO051813E
Convergent Synthesis of Naphthylisoquinoline Alkaloids: Total Synthesis of (+)-O-Methylancistrocline
Publisher: American Chemical Society (ACS)
Date: 1996
DOI: 10.1021/JO9607119
Abstract: A highly convergent synthesis of the methyl ether derivative 2a of the naphthylisoquinoline alkaloid ancistrocline (2) is described. The key step involves a stereoselective biaryl coupling between the chiral oxazoline 3 and the Grignard reagent 4 derived from the optically active tetrahydroisoquinoline 8. The atropisomeric mixture was then converted to the separable acetamides 11 and 12, which were obtained in a ratio of 16:84 and an overall yield of 32% for the three steps. The major atropisomer 12 was then converted into O-methylancistrocline (2a), which was identical to a semisynthetic s le derived from the related alkaloid ancistrocladinine (14).
Synthesis of acyloin natural products by Mukaiyama hydration
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D2OB00651K
Abstract: The preparation of Co( ii ) and Co( iii ) SALPN type catalysts for the Mukaiyama hydration of enones, and their application to the synthesis of acyloin natural products is described. An acyloin rearrangement was key to the success of this approach.
Total synthesis of a biotinylated rocaglate: Selective targeting of the translation factors eIF4AI/II
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.BMCL.2015.12.045
Abstract: The total synthesis of a biotinylated derivative of methyl rocaglate is described. This compound was accessed from synthetic methyl rocaglate (2) via formation of the propargyl amide and subsequent click reaction with a biotin azide. Affinity purification revealed that biotinylated rocaglate (8) and methyl rocaglate (2) bind with high specificity to translation factors eIF4AI/II. This remarkable selectivity is in line with that found for the more complex rocaglate silvestrol (3).
Formal total synthesis of the myxobacteria metabolite apicularen A via a transannular oxy-Michael addition
Publisher: Elsevier BV
Date: 07-2011
Asymmetric total synthesis of the myxobacteria metabolites crocacins A–D
Publisher: Elsevier BV
Date: 05-2008
Flow-Assisted Synthesis of Alkyl Citrate Natural Products
Publisher: No publisher found
Date: 2021
Formal Total Synthesis of Salicylihalamides A and B
Publisher: American Chemical Society (ACS)
Date: 13-02-2003
DOI: 10.1021/JO026798H
Abstract: An efficient synthesis of the macrolactone 3 of the salicylihalamides in 10 linear steps from alkene 6 is described. The key steps involved a Stille coupling between the chiral stannane 5 and benzyl bromide 4, which produced alkene 15 in good yield, and subsequent base-induced macrolactonization then gave compound 3. Macrolactone 3 was then converted into the known salicylihalamide A intermediate 18 in a three-step sequence. Compound 3 was also converted into another known salicylihalamide A and B intermediate 23 in a five-step sequence.
Synthesis of Novel Oligosaccharides Based on 1,4-Dioxanyloxy 3-Oxasugars
Publisher: The Japan Institute of Heterocyclic Chemistry
Date: 2012
Synthesis of 2,2-Disubstituted Furanoid Natural Products: Total Synthesis of Sphydrofuran
Publisher: American Chemical Society (ACS)
Date: 27-10-1998
DOI: 10.1021/JO9813336
Total Synthesis of (+)-Trachyspic Acid 19-n-Butyl Ester
Publisher: American Chemical Society (ACS)
Date: 17-02-2020
Total Synthesis of (+)-Crocacin A
Publisher: CSIRO Publishing
Date: 2003
DOI: 10.1071/CH03026
Abstract: The first asymmetric total synthesis of the electron-transport inhibitor crocacin A (1) is described. The key step involved acylation of the anion derived from dienecarbamate (6) with the acid chloride (5) to afford the enamide (14). Desilylation, oxidation, and N-deprotection gave acid (17), which was coupled with glycine methyl ester to afford (1).
Total synthesis of the marine sponge metabolites (+)-rottnestol, (+)-raspailol A and (+)-raspailol BTaken in part from the PhD thesis of I. R. Czuba, The University of Melbourne, 2002.
Publisher: Royal Society of Chemistry (RSC)
Date: 2003
DOI: 10.1039/B302460A
Abstract: The asymmetric syntheses of (+)-rottnestol (1) and the related marine sponge metabolites (+)-raspailols A (5) and B (6) are described. The key step in each of these sequences was a Stille coupling to form the C9-C10 sp2-sp2 bond and connect the polyene sidechains to the appropriate optically active tetrahydropyran core. For rottnestol (1), both C12 epimers were synthesised by a coupling between stannane 7 and (R)- or (S)-8 followed by acid hydrolysis which allowed for the assignment of the absolute configuration at the remote C12 stereocentre as R upon comparison of chiroptical data of the synthetic material with that reported for the natural product. In accord with this, (12R)-raspailol A (5) was synthesised from stannane 7 and sidechain 9 and this compound also compared well with the data for natural material including sign and absolute value of the specific rotation. Finally, the same C12 epimer of raspailol B (6) was secured via a union between stannane 10 and iodide 9 and this also possessed a similar rotation to that described for the natural product. Thus, all three compounds appear to possess the (12R) configuration, while that of the core tetrahydropyran ring is the same as proposed originally.
Synthesis of the C-1 sidechain of the squalestatins and zaragozic acid A
Publisher: Elsevier BV
Date: 10-1994
Total Synthesis of (−)-Reveromycin A
Publisher: American Chemical Society (ACS)
Date: 22-07-2004
DOI: 10.1021/OL048811L
Abstract: The asymmetric total synthesis of (-)-reveromycin A is described. The key steps involved a Lewis acid catalyzed inverse electron demand hetero-Diels-Alder reaction followed by hydroboration/oxidation to afford the spiroketal core 4 in a highly stereoselective manner and introduction of the C18 hemisuccinate by high-pressure acylation.
A novel, complex systems approach to modelling risk of psychological distress in young adolescents
Publisher: Springer Science and Business Media LLC
Date: 03-05-2021
DOI: 10.1038/S41598-021-88932-Y
Abstract: Adolescence is a period of significant anatomical and functional brain changes, and complex interactions occur between mental health risk factors. The Longitudinal Adolescent Brain Study commenced in 2018, to monitor environmental and psychosocial factors influencing mental health in 500 adolescents, for 5 years. Participants are recruited at age 12 from the community in Australia’s Sunshine Coast region. In this baseline, cross-sectional study of N = 64 participants, we draw on the network perspective, conceptualising mental disorders as causal systems of interacting entities, to propose a Bayesian network (BN) model of lifestyle and psychosocial variables influencing chances of in iduals being psychologically well or experiencing psychological distress. Sensitivity analysis of network priors revealed that psychological distress (Kessler-10) was most affected by eating behaviour. Unhealthy eating increased the chance of moderate psychological distress by 600%. Low social connectedness increased the chance of severe psychological disorder by 200%. Certainty for psychological wellness required 33% decrease in unhealthy eating behaviours, 11% decrease in low social connectedness, and 9% reduction in less physical activity. BN can augment clinician judgement in mental disorders as probabilistic decision support systems. The full potential of BN methodology in a complex systems approach to psychopathology has yet to be realised.
Convergent synthesis of polyether ionophore antibiotics: synthesis of the spiroketal and tricyclic glycal segments of monensin
Publisher: American Chemical Society (ACS)
Date: 08-1993
DOI: 10.1021/JA00069A013
Convergent synthesis of polyether ionophore antibiotics: protective manipulation and synthesis of monensin A
Publisher: American Chemical Society (ACS)
Date: 08-1993
DOI: 10.1021/JA00069A014
Synthetic approaches to the alkaloids of the ancistrocladacea: dehydroancistrocladisine
Publisher: Royal Society of Chemistry (RSC)
Date: 1989
DOI: 10.1039/C39890000301
The Stereoisomers of 5-Bromo-6,8-dimethoxy-1,2,3-trimethyl-1,2,3,4-tetrahydroisoquinoline. X-Ray Crystal-Structure of the trans Isomer
Publisher: CSIRO Publishing
Date: 1990
DOI: 10.1071/CH9900079
Abstract: Henry reaction between 3,5-dimethoxybenzaldehyde (2) and nitroethane gave (E)-2-(3,5-dimethoxyphenyl)-1-methyl-1-nitroethene (3). Under mild conditions the erythro and threo nitro aldols intermediate in this reaction could be isolated as their acetates. The threo isomer was obtained in diastereoisomeric excess. The nitrostyrene (3) was converted in several steps into cis-(20) and trans-5-bromo-6,8-dimethoxy-1,2,3-trimethyl-1,2,3,4-tetrahydroisoquinoline (18). The single-crystal X-ray structure of compound (18) is reported.
Synthesis of the C1–C18 Fragment of Rhizopodin: Late-State Introduction of the Oxazole
Publisher: American Chemical Society (ACS)
Date: 13-02-2014
DOI: 10.1021/OL500261N
Abstract: The synthesis of the C1-C18 fragment of the myxobacteria metabolite rhizopodin is described. Initial attempts at installing the E,E-diene via cross coupling with an oxazole fragment gave poor results. An alternative approach, in which the diene was formed prior and the oxazole introduced by an acylation/O,N-shift protocol, gave the C1-C18 fragment 2 of rhizopodin (1).
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