1) The document describes the total synthesis of the natural product 10-hydroxyasimicin, which contains a bis-THF motif in its central core.
2) A key step was the development of a template approach to link two alkenol building blocks and induce stereocontrol during ring-closing metathesis to generate the bis-THF framework.
3) The synthesis involved coupling the building blocks, ring-closing metathesis, asymmetric dihydroxylation, macrocycle opening and elaboration to install side chains, and final coupling and deprotection to yield the target natural product.
My Doctoral Thesis, titled "Advanced Oxidation Processes applied to mineralize Paracetamol, Chloroxylenol, Ibuprofen and Diclofenac in aqueous medium".
My Doctoral Thesis, titled "Advanced Oxidation Processes applied to mineralize Paracetamol, Chloroxylenol, Ibuprofen and Diclofenac in aqueous medium".
THE SOLID PHASE PEPTIDE SYNTHESIS IS SLIGHTLY DIFFRENT FROM PEPTIDE SYNTHESIS WHICH IS DISCUSSED HERE, ITS SYNTHESIS WITH STRUCTURE ANS BASICS ARE DISCUSSED WHICH WILL BE VERY USEFUL FOR READERS.
synthesis and spectral studies on cardanol based polyurethanesINFOGAIN PUBLICATION
Cardanol is a renewable organic resource obtained as a byproduct from the cashew industry. The present study has been carried out with an aim to manufacture rigid polyurethanes from natural and eco – friendly sources due to the rising prices of petrochemicals and also as an environmental concern. Vegetable oil based polyurethanes promising a new generation polymers which are low cost materials in the family of polyurethanes. Cardanol based phenolic resin has been synthesized by condensing cardanol with furfural in a particular mole ratio using phthalic acid as catalyst. The progress of the reaction was monitored by determining the free furfural and free phenol content. The resin was cured by using the curing agent 4, 41 - methylene bis(cyclohexyl isocyanate) and the catalyst dibutyltin dilaurate to produce polyurethane. Polyurethanes are an important class of polymers that have found place in many applications. The physico chemical and spectral properties of resin and polyurethane have also been studied.
Gelatin-grafted N- proflavine acryl amide was synthesized through two steps; firstly the Gelatin was grafted with
acrylic acid free radically using Ammonium per-sulfate at 60℃, Then it was modified to its corresponding acyl
chloride derivation, second step included the substitution with amino group of proflavine, in this research Gelatin
was used as a natural nontoxic, water soluble polymer as a drug carrier.
The prepared pro drug polymer was characterized by FTIR and 1H-NMR spectroscopies, Controlled drug release
was studied in different pH values at 37℃. Many advantages were obtained comparing with other known
methods.
Hypervalent refers to the main group elements that breaks the octet rule and firmly has more than right electrons in it's valence shell. These are non - metallic oxidation reagents.
International Journal of Pharmaceutical Science Invention (IJPSI)inventionjournals
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online
SDOA – Service Design and Organizational Activation. Enhanced lecture course Gatech 2012, Industrial Design. This presentation is part of the "breadth" part of the lecture series - designed to give service design students an understanding of business-relevant tools and concepts.
Elliot felix creating value with design strategyElliot Felix
Presentation / discussion prompt for Parsons Design Think Lab, introducing business models, value propositions, scenario planning, and Osterwalder's' Business Model Canvas
THE SOLID PHASE PEPTIDE SYNTHESIS IS SLIGHTLY DIFFRENT FROM PEPTIDE SYNTHESIS WHICH IS DISCUSSED HERE, ITS SYNTHESIS WITH STRUCTURE ANS BASICS ARE DISCUSSED WHICH WILL BE VERY USEFUL FOR READERS.
synthesis and spectral studies on cardanol based polyurethanesINFOGAIN PUBLICATION
Cardanol is a renewable organic resource obtained as a byproduct from the cashew industry. The present study has been carried out with an aim to manufacture rigid polyurethanes from natural and eco – friendly sources due to the rising prices of petrochemicals and also as an environmental concern. Vegetable oil based polyurethanes promising a new generation polymers which are low cost materials in the family of polyurethanes. Cardanol based phenolic resin has been synthesized by condensing cardanol with furfural in a particular mole ratio using phthalic acid as catalyst. The progress of the reaction was monitored by determining the free furfural and free phenol content. The resin was cured by using the curing agent 4, 41 - methylene bis(cyclohexyl isocyanate) and the catalyst dibutyltin dilaurate to produce polyurethane. Polyurethanes are an important class of polymers that have found place in many applications. The physico chemical and spectral properties of resin and polyurethane have also been studied.
Gelatin-grafted N- proflavine acryl amide was synthesized through two steps; firstly the Gelatin was grafted with
acrylic acid free radically using Ammonium per-sulfate at 60℃, Then it was modified to its corresponding acyl
chloride derivation, second step included the substitution with amino group of proflavine, in this research Gelatin
was used as a natural nontoxic, water soluble polymer as a drug carrier.
The prepared pro drug polymer was characterized by FTIR and 1H-NMR spectroscopies, Controlled drug release
was studied in different pH values at 37℃. Many advantages were obtained comparing with other known
methods.
Hypervalent refers to the main group elements that breaks the octet rule and firmly has more than right electrons in it's valence shell. These are non - metallic oxidation reagents.
International Journal of Pharmaceutical Science Invention (IJPSI)inventionjournals
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online
SDOA – Service Design and Organizational Activation. Enhanced lecture course Gatech 2012, Industrial Design. This presentation is part of the "breadth" part of the lecture series - designed to give service design students an understanding of business-relevant tools and concepts.
Elliot felix creating value with design strategyElliot Felix
Presentation / discussion prompt for Parsons Design Think Lab, introducing business models, value propositions, scenario planning, and Osterwalder's' Business Model Canvas
SDOA 3.2 The Language of Design and Corporate StakeholdersFlorian Vollmer
SDOA – Service Design and Organizational Activation. Enhanced lecture course Gatech 2012, Industrial Design. This presentation is part of the "breadth" part of the lecture series - designed to give service design students an understanding of business-relevant tools and concepts. Includes references to materials from DMI 2011.
How to create Design Strategy for a brandbala murugan
Method of creating Design Strategy with pictorial example
- factors to be consider
- analyze them with the right person
- Creativity Vs Research
- Who is the expert?
- The selling factor
- What is design strategy and what it includes?
A talk given at Adaptive Path's MX Conference in March 2010. Don't bother downloading or viewing the slides--they don't make sense without the audio. You have to do the Slidecast. C'mon, it's only 5 minutes!
Unfortunately, you can't hear the gasp from the audience when we got to slide 12.
Best Practices in Social Media for NGO's [Report]Social Samosa
As an NGO, your social media activities should aim at creating awareness, generating interest, encouraging sharing, and enlisting support and participationfor your initiatives.
Design Strategy: How information Can Drive Your Designs Decisions To SuccessSara Cannon
In this talk, seasoned creative director Sara Cannon will dive into the intersection of strategy and creativity through discussing how knowledge can inform design decisions. She will be looking at how different methods of research, data-collection, and strategical thinking can play into the creativity behind designs. And how at the end of the design process, you can measure success.
Facile Syntheses of Substituted, Conformationally-Constrained Benzoxazocines ...JamesSahn
A multicomponent assembly process (MCAP) was utilized to prepare versatile intermediates that are suitably functionalized for subsequent cyclizations via Ullmann and Heck reactions to efficiently construct substituted 2,6-methanobenzo[b][1,5]oxazocines and 1,6-methanobenzo[c]azocines, respectively. The intramolecular Ullmann cyclization was conducted in tandem with an intermolecular arylation that enabled the rapid syntheses of a number of O-functionalized methanobenzoxazocines.
Source: Tetrahedron Lett. 2011 December 21; 52(51): 6855–6858.
APPLICATIONS OF MULTICOMPONENT ASSEMBLY PROCESSES TO THE FACILE SYNTHESES OF ...JamesSahn
Several multicomponent assembly processes have been developed for the synthesis of intermediates that may be elaborated by a variety of cyclizations to generate a diverse array of highly functionalized heterocycles from readily-available starting materials. The overall approach enables the efficient preparation of libraries of small molecules derived from fused, privileged scaffolds. Source: Heterocycles 84:2 2012 pg 1089-1112
Novel coumarin isoxazoline derivatives: Synthesis and study of antibacterial ...Ratnakaram Venkata Nadh
A highly efficient and mild protocol for the syntheses of ethyl-3-
[7-benzyloxy-4-methyl-2-oxo-2H-8-chromenyl]-5-aryl-4,5-dihydro-4-
isoxazole carboxylates and ethyl-3-[7-benzyloxy-3-chloro-4-methyl-2-
oxo-2H-8-chromenyl]-5-aryl-4,5-dihydro-4-isoxazole carboxylates in
good yields via [3 þ 2] cycloaddition of in situ–generated nitrile
oxides from 7-benzyloxy-4-methyl-coumarin hydroxymoylchlorides
and 7-benzyloxy-3-chloro-4-methyl-coumarin hydroxymoylchlorides
respectively with ethyl-3-aryl prop-2-enoate has been developed.
The new compounds are screened for antibacterial activity.
A convenient new and efficient commercial synthetic route for dasatinib (Spry...Ratnakaram Venkata Nadh
A new and efficient synthetic route for dual-Src/Abl kinase inhibitor
dasatinib (Sprycel®), an anticancer drug, is described. This commercially
viable process yields dasatinib monohydrate free of potential impurities
with consistent yield of 68% in route A and 61% in route B with HPLC
purity >99.80% over four stages.
Similar to ACG-221-Synthesis-Asimicin-GSK-Novartis-Pfizer-Ley-cambridge university-uk-2005 (20)
This is a lecture by Dr. Jerry McLaughlin about his research into extracts of pawpaw plants, annonaceous acetogenins, in vitro, in vivo, mechanism of action, and toxicity in mice.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
Contact us if you are interested:
Email / Skype : kefaya1771@gmail.com
Threema: PXHY5PDH
New BATCH Ku !!! MUCH IN DEMAND FAST SALE EVERY BATCH HAPPY GOOD EFFECT BIG BATCH !
Contact me on Threema or skype to start big business!!
Hot-sale products:
NEW HOT EUTYLONE WHITE CRYSTAL!!
5cl-adba precursor (semi finished )
5cl-adba raw materials
ADBB precursor (semi finished )
ADBB raw materials
APVP powder
5fadb/4f-adb
Jwh018 / Jwh210
Eutylone crystal
Protonitazene (hydrochloride) CAS: 119276-01-6
Flubrotizolam CAS: 57801-95-3
Metonitazene CAS: 14680-51-4
Payment terms: Western Union,MoneyGram,Bitcoin or USDT.
Deliver Time: Usually 7-15days
Shipping method: FedEx, TNT, DHL,UPS etc.Our deliveries are 100% safe, fast, reliable and discreet.
Samples will be sent for your evaluation!If you are interested in, please contact me, let's talk details.
We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
1. Communications
Natural Products Synthesis
The Total Synthesis of the Annonaceous
Acetogenin 10-Hydroxyasimicin**
Gillian L. Nattrass, Elena Díez,
Matthew M. McLachlan, Darren J. Dixon, and
tether that could temporarily link two BDA-protected
Steven V. Ley*
alkenol building blocks 2 (BDA = 2,3-butanediacetal) of, in
principle, any desired stereochemical arrangement.[12] The
The annonaceous acetogenins comprise a class of almost 400 tether could then induce stereocontrol during the critical ring-
natural products that exhibit a remarkably broad spectrum of closing metathesis (RCM) to give compound 3.[13] Subsequent
biological activity. They function as insecticides, fungicides, Sharpless asymmetric dihydroxylation and chemoselective
herbicides, and, perhaps most importantly, in vivo antitumor cleavage of the tether would afford 4.[14] Intramolecular
agents and have been shown to overcome resistance in displacement by the unmasked hydroxy groups of the
multidrug-resistant tumors.[1] Structurally, the acetogenins are desymmetrized bistosylate 4 would yield the bis-THF unit 5.
characterized by a long lipophilic tail, a central polyoxy- Late-stage Sonogashira coupling of the terminal alkyne 6 and
genated core, and a terminal a,b-unsaturated g-lactone. The the butenolide 7 (constructed through a hetero-Diels–Alder
structural diversity in this family arises principally from (HDA) reaction to install the 1,5-stereochemical relationship
variations in the stereochemistry and connectivity of the and mask the butenolide double bond simultaneously, as
polyoxygenated central core, which can consist of one or more reported in our synthesis of muricatetrocin C)[10] would
tetrahydrofuranyl (THF) rings or, occasionally, a tetra-
hydropyranyl (THP) ring with various patterns of
hydroxylation. These variations and the stereochemical
consequences give rise to an impressive molecular
diversity within the family. Owing to their biological
activity and limited availability from natural sources,
these compounds have attracted worldwide attention
and have become the targets for total synthesis for a
number of research groups,[2–9] including our own.[10]
The majority of publications to date have focused on
the synthesis of individual members of the family that
suit a particular reaction type or stereochemical out-
come. Motivated by the bioactivity of the annonaceous
acetogenins, we embarked on a project to develop a
more general route that utilizes an orthogonal and
modular templating approach to provide access to many
members in the series. Herein we describe the first
successful synthesis of 10-hydroxyasimicin (1),[11] which
contains a bis-THF motif in the central core.
The crucial component in the synthesis of any of
these natural products is the stereoselective preparation
of the polyoxygenated central fragment. 10-Hydroxya-
simicin bears adjacent bis-THF rings flanked by two
hydroxy groups with a threo,trans,threo,trans,threo ster-
eochemistry. Our synthetic strategy to this oxygenated Scheme 1. Proposed synthetic route to 10-hydroxyasimicin (1). Ts = p-toluene-
arrangements (Scheme 1) hinged upon the design of a sulfonyl, MOM = methoxymethyl.
[*] G. L. Nattrass, E. Díez, M. M. McLachlan, D. J. Dixon,
Prof. Dr. S. V. Ley complete the carbon skeleton. Finally, selective hydrogena-
Department of Chemistry tion and global deprotection would furnish the natural
University of Cambridge product 1 (Scheme 1).
Lensfield Road, Cambridge, CB2 1EW (UK) Synthesis of fragment 2 began from (S,S)-dimethyl-d-
Fax: (+ 44) 1223-336-442
tartrate, which was readily converted into the monoprotected
E-mail: svl1000@cam.ac.uk
diol 8 in three steps according to a previously established
[**] We thank the Commonwealth Scholarship Commission in the
procedure (Scheme 2).[12] Subsequent tosylation of 8 and
United Kingdom for funding (G.L.N.), the EU for a Marie Curie
Fellowship (E.D.), GlaxoSmithKline (M.M.M.), Novartis for a treatment of the corresponding tosyl derivative with allyl-
research fellowship (S.V.L.), and Pfizer Global Research and magnesium bromide in the presence of CuBr afforded 2 in
Development for unrestricted funding towards the work. multigram quantities after deprotection with TBAF.
580 2005 Wiley-VCH Verlag GmbH Co. KGaA, Weinheim DOI: 10.1002/anie.200462264 Angew. Chem. Int. Ed. 2005, 44, 580 –584
2. Angewandte
Chemie
tion with phosphonate 15, which afforded an
E,E diene exclusively.[20] Exhaustive reduction of the
E,E diene with the Pearlman catalyst then afforded
saturated ester 12 in 94 % yield (Scheme 4). To
generate the last stereocenter, further chain extension
Scheme 2. Synthesis of alkenol 2. a) Reference [12]; b) NEt3, TsCl, DMAP,
CH2Cl2, 1.5 h, room temperature, 99 %; c) allylMgBr, CuBr, Et2O, 8 h, 0 8C, to propargylic ketone 13 was required. To this end
84 %; d) TBAF, THF, 5 h, 0 8C, 100 %. DMAP = 4-(dimethylamino)pyridine, ketone 13 was obtained by conversion of the saturated
TBAF = tetrabutylammonium fluoride. ester into the Weinreb amide,[21] which was then
The next step in the synthesis involved the development
of a suitable template to link the two alkenol molecules
together in order to proceed with an intramolecular meta-
thesis reaction. As mentioned earlier, we required a tether-
ing unit that could adjust the conformation of the macro-
cycle to control the stereoselectivity during the RCM
reaction.[13] The chosen tethering template should behave as
a “molecular workbench” and help orientate the olefin so
that one face is preferentially available for attack during a
syn-stereoselective dihydroxylation reaction.[14] Further-
more, the tether would play the role of a protecting group
upon cleavage of the macrocycle to enable desymmetriza-
tion of the core. Hence the unit had to be dissymmetric to
allow orthogonal cleavage upon completion of the dihy-
droxylation. On top of this, a dissymmetric tethering unit
would enable us to attach different BDA-protected alkenol
units sequentially to produce acetogenins with alternative
stereochemistries at the core.[15] To put these concepts into
effect, a differentiated arene with orthogonal substituents
was chosen, as we could fine-tune the macrocycle ring size
simply by varying the substitution pattern of the aryl
system. 4-Bromomethylbenzoyl chloride was found to give
the best results and was used in all subsequent investiga-
tions.[16]
Scheme 3. Synthesis of bis-THF framework 5. a) KHMDS, THF, 5 h, À78!0 8C,
Coupling of alkenol 2 with 4-bromomethylbenzoyl 69 %; b) second-generation Grubbs catalyst, CH2Cl2, 1 h, reflux, 99 %; c) AD-mix-a,
chloride in the presence of KHMDS gave the doubly MeSO2NH2, NaHCO3, tBuOH/H2O (1/1), 96 h, 0 8C!RT, 96 % (S,S/R,R 16:1);
loaded para-linked diene 9 in 69 % yield. Subsequent d) TsCl, pyridine, 20 h, 0 8C!RT, 90 %; e) NaOMe, MeOH, 44 h, room temperature,
treatment of 9 with a second-generation Grubbs catalyst[17] 93 %; f) DMSO, (COCl)2, CH2Cl2, À78 8C; NEt3, À78 8C!RT, 98 %;
in dichloromethane at reflux delivered the intramolecular g) CH3(CH2)8PPh3Br, nBuLi, THF, 7 h, À78!0 8C, 69 %; h) TFA/H2O (2:1), 5 min
metathesis product in excellent yield, exclusively as the (repeat twice), room temperature; i) K2CO3, MeOH, 3.5 h, reflux, 80 % over two
steps; j) MOMCl, Hünig base, DMAP, CH2Cl2, 18 h, 0 8C!RT, 78 %; k) Pd/C,
E adduct. Sharpless asymmetric dihydroxylation of the
HCO2ÀNH4+, MeOH, 2 h, reflux, 79 %. HMDS = hexamethyldisilazide,
olefin with AD-mix-a afforded the diol in a diastereomeric DMSO = dimethyl sulfoxide, TFA = trifluoroacetic acid.
ratio of 16:1 favoring the desired S,S product (Scheme 3).[18]
Treatment of the diol with TsCl in pyridine afforded the
ditosylated compound 10 in 90 % yield. treated with the lithium derivative of trimethylsilylacetylene
The macrocycle was opened by treatment of 10 with followed by desilylation with TBAF to give 13 in 60 % yield
sodium methoxide in methanol at room temperature to afford over the two steps.[22] Diastereoselective oxazaborolidine-
the primary alcohol.[19] Swern oxidation and a subsequent catalyzed (CBS)[23] reduction gave 6 in 78 % yield, with an
Wittig reaction installed the nine-membered carbon side- excellent ratio favoring the desired isomer (44:1).
chain terminus as the Z olefin 4. Removal of the BDA groups With the synthesis of fragment 6 completed, we now
followed by an intramolecular Williamson cyclization with turned our attention to the synthesis of butenolide 7 in
potassium carbonate as the base led to the formation of the preparation for the final coupling reaction. Diene 17 was
bis-THF core 11 in 80 % yield over the two steps. Finally, synthesized in seven steps from 1,4-butanediol according to a
protection of the free secondary alcohols with MOMCl, previously established procedure (Scheme 5).[10] As in our
followed by parallel reduction of the double bond and synthesis of muricatetrocin C, the 1,5-stereochemical rela-
debenzylation under transfer-hydrogenation conditions com- tionship in the butenolide moiety was installed through the
pleted the synthesis of fragment 5 (Scheme 3). HDA reaction with nitrosobenzene at 0 8C which afforded an
Fragment 5 was further elaborated by Dess–Martin inseparable 7:3 mixture of regioisomers favoring the desired
oxidation, followed by Horner–Wadsworth–Emmons olefina- adduct 18.[24] The NÀO bond was cleaved by using freshly
Angew. Chem. Int. Ed. 2005, 44, 580 –584 www.angewandte.org 2005 Wiley-VCH Verlag GmbH Co. KGaA, Weinheim 581
3. Communications
man catalyst afforded the free alcohol. Oxidation of
the released primary alcohol with TPAP,[26] fol-
lowed by one-carbon homologation, according to
the Takai procedure,[27] provided the vinyl iodide 20
as a mixture of isomers (3.7:1 ratio favoring the
E geometry) in 59 % yield over two steps. Subse-
quent elimination of the trifluoroacetamide group
in the presence of DBU in acetonitrile at 0 8C
afforded fragment 7 without epimerization of the
butenolide methyl substituent (Scheme 5).
Sonogashira cross-coupling of vinyl iodide 7
with the propargylic alcohol 6 proceeded smoothly
to produce the skeleton 14 in 86 % yield
(Scheme 4).[28] The enyne functional group was
reduced selectively over the butenolide double
bond by using the Wilkinson catalyst to afford the
protected acetogenin in 74 % yield. Final global
deprotection with BF3·Et2O in methyl sulfide
afforded 1 as a colorless wax in 68 % yield. The
spectroscopic data for synthetic 1 (1H NMR,
13
C NMR, IR, MS, and specific rotation)[29] were
Scheme 4. Synthesis of 10-hydroxyasimicin (1). a) DMP, NaHCO3, CH2Cl2, 1 h, 0 8C!RT, in excellent agreement with those reported for
95 %; b) 15, NaHMDS, THF, 18 h, À78 8C!RT, 81 %; c) Pd(OH)2/C, H2, THF, 1 h, room naturally occurring 10-hydroxyasimicin (1).[11]
temperature, 94 %; d) Me(MeO)NH·HCl, iPrMgCl, THF, 1.5 h, À10 8C, 82 %; e) trimethylsilyl- In conclusion, the successful synthesis of 10-
acetylene, nBuLi, THF, 1 h, À78!0 8C; f) TBAF, THF, 20 min, À20 8C, 60 % over two steps;
hydroxyasimicin (1) demonstrates the potential of
g) (S)-16, BH3·Me2S, THF, 1 h, À35 8C, 78 % (S/R 44:1); h) [Pd(PPh3)2Cl2], CuI, NEt3, 45 min,
room temperature, 86 %; i) [Rh(PPh3)3Cl], H2, benzene/EtOH (1:1), 23 h, room temperature,
the template approach to the oxygenated core of
74 %; j) BF3·OEt2, Me2S, 20 min, room temperature, 68 %. DMP = Dess–Martin periodinane. the acetogenins in an efficient and easily adapted
manner. This route provides an efficient method for
the construction of the bis-THF moiety incorporat-
prepared [Mo(CO)3(MeCN)3] in the presence of water at ing a tether that enhances the stereochemical outcome of the
room temperature.[25] Protection of the resultant secondary RCM step and enables desymmetrization of the central
hydroxy group as a MOM ether enabled the separation of the fragment for further chain extension. The TBS-protected diol
regio- and stereoisomers through flash-column chromatog- building block 8, arising from (R,R,S,S)-2,3-BDA-protected
raphy, thus avoiding the need for the laborious preparative (S,S)-dimethyl-d-tartrate, and the highly diastereoselective
HPLC separation required in the previous synthesis of HDA approach to the butenolide unit are usefully employed
muricatetrocin C. Subsequent hydrogenation over catalytic in this new synthesis of an acetogenin natural product.
palladium and protection of the amine as the trifluoroaceta- Further applications of these general approaches will be
mide afforded compound 19. Debenzylation with the Pearl- employed in the preparation of other members of the
acetogenin series in due course.
Received: October 11, 2004
Published online: December 13, 2004
.
Keywords: metathesis · natural products · templating effect ·
total synthesis
[1] a) F. Q. Alali, X.-X. Liu, J. L. McLaughlin, J. Nat. Prod. 1999, 62,
504; b) N. H. Oberlies, V. L. Croy, M. L. Harrison, J. L.
McLaughlin, Cancer Lett. 1997, 15, 73; c) L. Zeng, Q. Ye, N. H.
Oberlies, G. Shi, Z. Gu, K. He, J. L. McLaughlin, Nat. Prod. Rep.
1996, 13, 275, and references therein.
Scheme 5. Synthesis of butenolide 7. a) Reference [10]; b) [Mo(CO)6], MeCN, 4 h, [2] For recent reviews, see: a) G. Cassiraghi, F. Zanardi, L.
reflux; then 18, H2O, 15 min, room temperature; c) MOMCl, Hünig base, DMAP, Battistini, G. Rassu, G. Appendino, Chemtracts: Org. Chem.
CH2Cl2, 16 h, 0 8C!RT, 20 % over three steps, including HDA; d) Pd/C, H2, THF, 1998, 11, 803; b) J. A. Marshall, K. W. Hinkle, C. E. Hagedorn,
2 h, room temperature, 100 %; e) TFAA, Hünig base, CH2Cl2, 30 min, 0 8C, 74 %; Isr. J. Chem. 1997, 37, 97; c) R. Hoppe, H. D. Scharf, Synthesis
f) Pd(OH)2/C, H2, MeOH, 30 min, room temperature, 99 %; g) TPAP, NMO, NEt3, 1995, 1447; d) B. Figad›re, Acc. Chem. Res. 1995, 28, 359, and
CH2Cl2, 2 h, room temperature, 84 %; h) CrCl2, CHI3, THF, 17 h, 0 8C!RT, 70 % references therein.
(E/Z 3.7:1); i) DBU, CH3CN, 6 h, À15!À5 8C (60 %). TFAA = trifluoroacetic [3] For syntheses from 1998, see: a) P. Neogi, T. Doundoulakis, A.
anhydride, TPAP = tetrapropylammonium perruthenate, DBU = 1,8-diazo- Yazbak, S. C. Sinha, E. Keinan, J. Am. Chem. Soc. 1998, 120,
bicyclo[5.4.0]undec-7-ene. 11 279; b) S. C. Sinha, A. Sinha, E. Keinan, J. Am. Chem. Soc.
582 2005 Wiley-VCH Verlag GmbH Co. KGaA, Weinheim www.angewandte.org Angew. Chem. Int. Ed. 2005, 44, 580 –584
4. Angewandte
Chemie
1998, 120, 4017; c) S. Sasaki, K. Maruta, H. Naito, R. Maemura, W. R. Lin, H. F. Chiu, Y. C. Wu, K. S. Wang, M. J. Wu,
E. Kawahara, M. Maeda, Chem. Pharm. Bull. 1998, 46, 154; Tetrahedron Lett. 2003, 44, 7833; l) S. R. V. Kandula, P. Kumar,
d) J. A. Marshall, H. J. Jiang, J. Org. Chem. 1998, 63, 7066; e) A. Tetrahedron Lett. 2003, 44, 6149.
Yazbak, S. C. Sinha, E. Keinan, J. Org. Chem. 1998, 63, 5863; [9] For syntheses from 2004, see: a) N. Maezaki, H. Tominaga, N.
f) S. E. Schaus, J. Branalt, E. N. Jacobsen, J. Org. Chem. 1998, 63, Kojima, M. Yanai, D. Urabe, T. Tanaka, Chem. Commun. 2004,
4876; g) S. Hanessian, T. A. Grillo, J. Org. Chem. 1998, 63, 1049; 406; b) H. N. Han, M. K. Sinha, L. J. DSouza, E. Keinan, S. C.
h) H. Makabe, A. Tanaka, T. Oritani, Tetrahedron 1998, 54, 6329; Sinha, Chem. Eur. J. 2004, 10, 2149; c) Q. S. Zhang, H. J. Lu, C.
i) J. A. Marshall, H. J. Jiang, Tetrahedron Lett. 1998, 39, 1493; Richard, D. P. Curran, J. Am. Chem. Soc. 2004, 126, 36; d) A. R.
j) J. A. Marshall, K. W. Hinkle, Tetrahedron Lett. 1998, 39, 1303. Cecil, Y. L. Hu, M. J. Vicent, R. Duncan, R. C. D. Brown, J. Org.
[4] For syntheses from 1999, see: a) S. Bäurle, S. Hoppen, U. Koert, Chem. 2004, 69, 3368; e) L. Zhu, D. R. Mootoo, J. Org. Chem.
Angew. Chem. 1999, 111, 1341; Angew. Chem. Int. Ed. 1999, 38, 2004, 69, 3154; f) T. Yoshimitsu, T. Makino, H. Nagaoka, J. Org.
1263; b) W. Kuruyama, K. Ishigami, T. Kitahara, Heterocycles Chem. 2004, 69, 1993; g) H. Makabe, A. Miyawaki, R. Takaha-
1999, 50, 981; c) J. A. Marshall, H. J. Jiang, J. Nat. Prod. 1999, 62, shi, Y. Hattori, M. Abe, H. Miyoshi, Tetrahedron Lett. 2004, 45,
1123; d) S. C. Sinha, E. Keinan, J. Org. Chem. 1999, 64, 7067; 973.
e) Q. Yu, Z. J. Yao, X. G. Chen, Y. L. Wu, J. Org. Chem. 1999, 64, [10] a) D. J. Dixon, S. V. Ley, D. J. Reynolds, Angew. Chem. 2000,
2440; f) A. Sinha, S. C. Sinha, E. Keinan, J. Org. Chem. 1999, 64, 112, 3768; Angew. Chem. Int. Ed. 2000, 39, 3622; b) D. J. Dixon,
2381; g) J. A. Marshall, H. J. Jiang, J. Org. Chem. 1999, 64, 971; S. V. Ley, D. J. Reynolds, Chem. Eur. J. 2002, 8, 1621.
h) S. Takahashi, K. Maeda, S. Hirota, T. Nakata, Org. Lett. 1999, [11] K. He, G. Shi, G.-X. Zhao, L. Zeng, Q. Ye, J. T. Schwedler, K. V.
1, 2025; i) T. S. Hu, Q. Lin, Y. L. Wu, Y. K. Wu, Org. Lett. 1999, 1, Wood, J. L. McLaughlin, J. Nat. Prod. 1996, 59, 1029.
399; j) Q. Yu, Y. K. Wu, H. Ding, Y. L. Wu, J. Chem. Soc. Perkin [12] S. V. Ley, D. K. Baeschlin, D. J. Dixon, A. C. Foster, S. J. Ince,
Trans. 1 1999, 1183; k) Z. M. Wang, S. K. Tian, M. Shi, H. W. M. Priepke, D. J. Reynolds, Chem. Rev. 2001, 101, 53; and
Tetrahedron: Asymmetry 1999, 10, 667; l) W. Q. Yang, T. references therein.
Kitahara, Tetrahedron Lett. 1999, 40, 7827; m) U. Emde, U. [13] a) Y. Sakamoto, M. Okazaki, K. Miyamoto, T. Nakata, Tetrahe-
Koert, Tetrahedron Lett. 1999, 40, 5979; n) Z. M. Wang, S. K. dron Lett. 2001, 42, 7633; b) E. C. Hansen, D. Lee, J. Am. Chem.
Tian, M. Shi, Tetrahedron Lett. 1999, 40, 977; o) S. Takahashi, T. Soc. 2003, 125, 9582; c) P. A. Evans, J. Cui, G. P. Buffone, Angew.
Nakata, Tetrahedron Lett. 1999, 40, 727; p) Z. M. Ruan, D. R. Chem. 2003, 115, 1776 – 1779; Angew. Chem. Int. Ed. 2003, 42,
Mootoo, Tetrahedron Lett. 1999, 40, 49. 1734, and references therein.
[5] For syntheses from 2000, see: a) S. Hoppen, S. Bäurle, U. Koert, [14] a) J. Mulzer, K. Schein, J. W. Bats, J. Buschmann, P. Luger,
Chem. Eur. J. 2000, 6, 2382; b) S. Bäurle, U. Peters, T. Friedrich, Angew. Chem. 1998, 110, 1625; Angew. Chem. Int. Ed. 1998, 37,
U. Koert, Eur. J. Org. Chem. 2000, 2207; c) U. Emde, U. Koert, 1566; b) J. Mulzer, I. Böhm, J. W. Bats, Tetrahedron Lett. 1998,
Eur. J. Org. Chem. 2000, 1889; d) Z. M. Wang, S. K. Tian, M. Shi, 39, 9643.
Eur. J. Org. Chem. 2000, 349; e) Z. M. Wang, S. K. Tian, M. Shi, [15] In this particular synthesis, the two alkenol units are the same,
Chirality 2000, 12, 581; f) M. Szlosek, J. F. Peyrat, C. Chaboche, but any absolute configurational arrangement can, in principle,
X. Franck, R. Hocquemiller, B. Figad›re, New J. Chem. 2000, 24, be loaded onto the orthogonal 4-bromomethylbenzyl chloride
337; g) W. Q. Yang, T. Kitahara, Tetrahedron 2000, 56, 1451; template by making use of the greater reactivity of the acyl
h) T.-S. Hu, Y.-L. Wu, Y. Wu, Org. Lett. 2000, 2, 887. chloride relative to the alkyl bromide substituent.
[6] For syntheses from 2001, see: a) C. Harken, R. Bruckner, New J. [16] A noticeable improvement in stereocontrol was observed in
Chem. 2001, 25, 40; b) T.-S. Hu, Q. Yu, Y.-L. Wu, Y. Wu, J. Org. going from ortho to meta and finally to para substitution. The
Chem. 2001, 66, 853; c) N. Maezaki, N. Kojima, A. Sakamoto, C. results of these investigations will be published in a full paper at
Iwata, T. Tanaka, Org. Lett. 2001, 3, 429; d) S. D. Burke, L. Jiang, a later date.
Org. Lett. 2001, 3, 1953. [17] M. Scholl, S. Ding, C. W. Lee, R. H. Grubbs, Org. Lett. 1999, 1,
[7] For syntheses from 2002, see: a) S. Takahashi, A. Kubota, T. 953.
Nakata, Angew. Chem. 2002, 114, 4945; Angew. Chem. Int. Ed. [18] Comparable diastereoselectivity was obtained in the Sharpless
2002, 41, 4751; b) S. Takahashi, T. Nakata, J. Org. Chem. 2002, asymmetric dihydroxylation reaction when performed on the
67, 5739; c) S. Jiang, Z.-H. Liu, G. Sheng, B.-B. Zeng, X.-G. open chain hydroxy ester, obtained from the transesterfiction
Cheng, Y.-L. Wu, Z.-J. Yao, J. Org. Chem. 2002, 67, 3404; reaction on the alkene formed immediately after the RCM
d) A. R. L. Cecil, R. C. D. Brown, Org. Lett. 2002, 4, 3715; e) H. reaction.
Makabe, Y. Hattori, A. Tanoka, T. Oritani, Org. Lett. 2002, 4, [19] Orthogonal macrocycle opening was achieved under transfer-
1083; f) E. Keinan, S. C. Sinha, Pure Appl. Chem. 2002, 74, 93; hydrogenation conditions and will be communicated in a full
g) S. Takahashi, A. Kubota, T. Nakata, Tetrahedron Lett. 2002, paper at a later date.
43, 8661. [20] a) D. B. Dess, J. C. Martin, J. Org. Chem. 1983, 48, 4155; b) D. B.
[8] For syntheses from 2003, see: a) N. Maezaki, N. Kojima, A. Dess, J. C. Martin, J. Am. Chem. Soc. 1991, 113, 7277.
Sakamoto, H. Tominaga, C. Iwata, T. Tanaka, M. Monden, B. [21] J. M. Williams, R. B. Jobson, N. Yasuda, G. Marchesini, U.-H.
Damdinswen, S. Nakamori, Chem. Eur. J. 2003, 9, 390; b) B.-B. Dolling, E. J. J. Grabowski, Tetrahedron Lett. 1995, 36, 5461.
Zeng, Y. Wu, S. Jiang, Q. Yu, Z.-J. Yao, Z.-H. Liu, H.-Y. Li, Y. Li, [22] M. Muller, A. Mann, M. Taddei, Tetrahedron Lett. 1993, 34, 3289.
X.-G. Chen, Y.-L. Wu, Chem. Eur. J. 2003, 9, 282; c) P. A. Evans, [23] E. J. Corey, R. K. Bakshi, S. J. Shibata, J. Am. Chem. Soc. 1987,
J. Cui, S. J. Gharpure, A. Polosukhi, H. R. Zhang, J. Am. Chem. 109, 5551.
Soc. 2003, 125, 14 072; d) J. A. Marshall, A. Piettre, M. A. Paige, [24] Investigations into using alternative nitrosodienophiles to
F. Valeriate, J. Org. Chem. 2003, 68, 8290; e) J. A. Marshall, A. improve the regioselectivity of the desired HDA reaction
Piettre, M. A. Paige, F. Valeriate, J. Org. Chem. 2003, 68, 1780; indicated that nitrosobenzene gives the most favorable results
f) J. A. Marshall, A. Piettre, M. A. Paige, F. Valeriate, J. Org. and could not be improved on. These results will be communi-
Chem. 2003, 68, 1771; g) L. Zhu, D. R. Mootoo, Org. Lett. 2003, cated in a full paper at a later date.
5, 3475; h) S. Takahashi, A. Kubota, T. Nakata, Org. Lett. 2003, 5, [25] a) M. Nitta, T. Kobayashi, J. Chem. Soc. Perkin Trans. 1 1985,
1353; i) R. V. A. Orru, B. Groenendaal, J. van Heyst, M. Hunt- 1401; b) S. Cicchi, A. Goti, A. Brondi, A. Guarna, F. De Sarlo,
ing, C. Wesseling, R. F. Schmitz, S. F. Mayer, K. Faber, Pure Tetrahedron Lett. 1990, 31, 3351.
Appl. Chem. 2003, 75, 259; j) S. Takahashi, A. Kubota, T. Nakata, [26] S. V. Ley, J. Norman, W. P. Griffith, S. P. Marsden, Synthesis
Tetrahedron 2003, 59, 1627; k) J. L. Lee, C. F. Lin, L. Y. Hsieh, 1994, 639.
Angew. Chem. Int. Ed. 2005, 44, 580 –584 www.angewandte.org 2005 Wiley-VCH Verlag GmbH Co. KGaA, Weinheim 583
5. Communications
[27] K. Takai, K. Nitta, K. Utimoto, J. Am. Chem. Soc. 1986, 108,
7408.
[28] a) T. R. Hoye, P. R. Hanson, A. C. Kovelesky, T. D. Ocain, Z. P.
Zhuang, J. Am. Chem. Soc. 1991, 113, 9369; b) K. Sonogashira,
Y. Thoda, N. Magihara, Tetrahedron Lett. 1975, 4467.
[29] Spectroscopic data for synthetic 1, a colorless wax: [a]25 = + 16
D
(c = 0.25 in CHCl3, lit. [11] [a]22 = + 17.3 in CHCl3); 1H NMR
D
(400 MHz; CDCl3): d = 7.18 (d, J = 1.3 Hz, 1 H; 35-H), 5.05 (qd,
J = 6.8, 1.4 Hz, 1 H; 36-H), 3.86 (m, 5 H; 16-H, 19-H, 20-H, 23-
H), 3.60 (m, 1 H; 10-H), 3.41–3.38 (m, 2 H; 15-H, 24-H), 2.53
(dddd, J = 15.2, 3.2, 1.5, 1.5 Hz, 1 H; 3a-H), 2.40 (dddd, J = 15.1,
8.3, 1.2, 1.2 Hz, 1 H; H-3b), 1.97 (m, 8 H; 17-H, 18-H, 21-H, 22-
H), 1.70–1.26 (m, 36 H; 5–9-H, 1–14-H, 25–33-H), 1.43 (d, J =
6.7 Hz, 3 H; 37-H), 0.88 ppm (t, J = 6.7 Hz, 3 H; 34-H); 13C NMR
(125 MHz; CDCl3): d = 174.6 (C1), 151.8 (C35), 131.2 (C2), 83.2,
83.1 (C16, C23), 81.81, 81.75 (C19, C20), 78.0 (C36), 74.1, 74.0
(C15, C24), 71.7 (C10), 69.9 (C4), 37.34 (C5), 37.3 (C11), 37.2
(C9), 33.41, 33.36, 33.32 (C3, C14, C25), 31.9 (C32), 29.71, 29.61,
29.60, 29.59, 29.47, 29.32 (C6–C8, C12, C13, C26–C31), 29.0
(C21, C18), 28.3 (C17, C22), 25.64, 25.62, 25.5 (C6–C8, C12, C13,
C26–C31), 22.7 (C33), 19.1 (C37), 14.1 ppm (C34); IR (thin
film): nmax = 3404 br (OH), 2924, 2853 (CH), 1753 (C=O) cmÀ1;
˜
HRMS: calcd for C37H66O8Na [M+Na]+: 661.4650; found:
661.4651.
584 2005 Wiley-VCH Verlag GmbH Co. KGaA, Weinheim www.angewandte.org Angew. Chem. Int. Ed. 2005, 44, 580 –584