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Showing posts with label total synthesis. Show all posts
Showing posts with label total synthesis. Show all posts

Thursday, 19 June 2014

Longifolene total synthesis by Corey

File:Longifolene total synthesis by Corey.svg

Longifolene is the common (or trivial) chemical name of a naturally occurring, oily liquid hydrocarbon found primarily in the high-boiling fraction of certain pine resins. The name is derived from that of a pine species from which the compound was isolated,[1] Pinus longifolia (obsolete name for Pinus roxburghii Sarg.)[2]
Chemically, longifolene is a tricyclic sesquiterpene. This molecule is chiral, and the enantiomer commonly found in pines and other higher plants exhibits a positive optical rotation of +42.73°. The other enantiomer (optical rotation −42.73°) is found in small amounts in certain fungi and liverworts.
Longifolene is used in organic synthesis for the preparation of dilongifolylborane,[3] a chiral hydroborating agent.
Longifolene is also one of two most abundant aroma constituents of lapsang souchong tea, because the tea is smoked over pine Due to the compact tricyclic structure and lack of functional groups, Longifolene is an attractive target for research groups highlighting new synthetic methodologies. Notable syntheses are by Corey,[5][6] McMurray,[7] Johnson,[8] Oppolzer,[9] and Schultz.[10]
Chemical structure of Longifolene

Longifolene total synthesis by Corey


Author Elias J. Corey
Publication year 1961
Synthesis type Total synthesis
Number of steps 14 (linear)



 Total synthesis of Longifolene:

Reference:Corey, E. J.; Ohno, M.; Mitra, R. B.; Vatakencherry, P. A. J. Am. Chem. Soc. 1964, 86, 478. DOI
Keywords: Ketone → Ketal • CompE+-Ketone/Ketone+glycol • O-H → O-SO2R • Ketone → Ketal(thio) • Ketone → Alkyl-OH • Alkyl-OH → Ketone • Li-Me+Ketone • Ketone+Li-Alkyl • Dehydration → Ene • Wittig-alkyl+Ketone • Alkene → Diol-1,2 • CompNu-Alcohol/Alcohol+RSO2Cl • Pinacol • ConjAdd Enolate • Ketone enolate+Enone • Hydrogenolysis C-S • Ketone → CH2
Reagents:Wieland-Miescher • Glycol • TsOH • PPh3=CH-Me • OsO4 • TsCl, Py • LiClO4 • Carbonate, calcium • HCl, H2O • NEt3 • NaCPh3 • MeI • Thiol, (CH2)2-SH • BF3·OEt2 • AlH4-Li+ • Hydrazine • CrO3 • MeLi • SOCl2


The biosynthesis of longifolene begins with farnesyl diphosphate (1) (also called farnesyl pyrophosphate) by means of a cationic polycyclization cascade. Loss of the pyrophosphate group and cyclization by the distal alkene gives intermediate 3, which by means of a 1,3-hydride shift gives intermediate 4. After two additional cyclizations, intermediate 6 produces longifolene by a 1,2-alkyl migration.

CAS number 475-20-7 Yes
ChemSpider 1406720 Yes
Jmol-3D images Image 1
Molecular formula C15H24
Molar mass 204.36 g/mol
Density 0.928 g/cm3
Boiling point 254 °C (706 mm Hg)

 1,4-Methanoazulene, Junipen, (+)-Longifolene, 475-20-7, 3,3,7-trimethyl-8-methylenetricyclo[,9]undecane, Kuromatsuen, Kuromatsuene 
Molecular Formula: C15H24   Molecular Weight: 204.35106
The borane derivative dilongifolylborane is used in organic synthesis as a chiral hydroborating agent.[12]
  1. Naffa, P.; Ourisson, G. Bulletin de la Société chimique de France, 1954, 1410.
  2. Simonsen, J. L. J. Chem. Soc. 1920, 117, 570.
  3. Jadhav, P. K.; Brown, H. C. J. Org. Chem. 1981, 46, 2988.
  4. Shan-Shan Yao; Wen-Fei Guo; YI Lu; Yuan-Xun Jiang, "Flavor Characteristics of Lapsang Souchong and Smoked Lapsang Souchong,a Special Chinese Black Tea with Pine Smoking Process", Journal of Agricultural and Food Chemistry, Vol. 53, No.22, (2005)
  5. Corey, E. J. et al. J. Am. Chem. Soc. 1961, 83, 1251.
  6. Corey, E. J. et al. J. Am. Chem. Soc. 1964, 86, 478.
  7. McMurray, J. E.; Isser, S. J. J. Am. Chem. Soc. 1972, 94, 7132.
  8. Volkermann, R. A.; Andrews, G. C.; Johnson, W. S. J. Am. Chem. Soc. 1975, 97, 4777-4779.
  9. Oppolzer, W.; Godel, T. J. Am. Chem. Soc. 1978, 100, 2583.
  10. Schultz, A. G. et al. J. Org. Chem. 1985, 50, 915.
  11. Ho, Gregory J. Org. Chem. 2005, 70, 5139 -5143.
  12. Dev, Sukh (1981). "Aspects of longifolene chemistry. An example of another facet of natural products chemistry". Accounts of Chemical Research 14 (3): 82–88. doi:10.1021/ar00063a004.

Friday, 2 August 2013


A chemist in the 1950s using column chromatography. The Erlenmeyer receptacles are on the floor.
Column chromatography in chemistry is a method used to purify individual chemical compounds from mixtures of compounds. It is often used for preparative applications on scales from micrograms up to kilograms. The main advantage of column chromatography is the relatively low cost and disposability of the stationary phase used in the process. The latter prevents cross-contamination and stationary phase degradation due to recycling.
The classical preparative chromatography column, is a glass tube with a diameter from 5 mm to 50 mm and a height of 5 cm to 1 m with a tap and some kind of a filter (a glass frit or glass wool plug – to prevent the loss of the stationary phase) at the bottom. Two methods are generally used to prepare a column: the dry method, and the wet method.
  • For the dry method, the column is first filled with dry stationary phase powder, followed by the addition of mobile phase, which is flushed through the column until it is completely wet, and from this point is never allowed to run dry.
  • For the wet method, a slurry is prepared of the eluent with the stationary phase powder and then carefully poured into the column. Care must be taken to avoid air bubbles. A solution of the organic material is pipetted on top of the stationary phase. This layer is usually topped with a small layer of sand or with cotton or glass wool to protect the shape of the organic layer from the velocity of newly added eluent. Eluent is slowly passed through the column to advance the organic material. Often a spherical eluent reservoir or an eluent-filled and stoppered separating funnel is put on top of the column.
The individual components are retained by the stationary phase differently and separate from each other while they are running at different speeds through the column with the eluent. At the end of the column they elute one at a time. During the entire chromatography process the eluent is collected in a series of fractions. Fractions can be collected automatically by means of fraction collectors. The productivity of chromatography can be increased by running several columns at a time. In this case multi stream collectors are used. The composition of the eluent flow can be monitored and each fraction is analyzed for dissolved compounds, e.g. by analytical chromatography, UV absorption, or fluorescence. Colored compounds (or fluorescent compounds with the aid of an UV lamp) can be seen through the glass wall as moving bands.


    Stationary phase

    The stationary phase or adsorbent in column chromatography is a solid. The most common stationary phase for column chromatography is silica gel, followed by aluminaCellulosepowder has often been used in the past. Also possible are ion exchange chromatographyreversed-phase chromatography(RP), affinity chromatography or expanded bed adsorption(EBA). The stationary phases are usually finely ground powders or gels and/or are microporous for an increased surface, though in EBA a fluidized bed is used. There is an important ratio between the stationary phase weight and the dry weight of the analyte mixture that can be applied onto the column. For silica column chromatography, this ratio lies within 20:1 to 100:1, depending on how close to each other the analyte components are being eluted.

    Mobile phase (eluent)

    The mobile phase or eluent is either a pure solvent or a mixture of different solvents. It is chosen so that the retention factor value of the compound of interest is roughly around 0.2 - 0.3 in order to minimize the time and the amount of eluent to run the chromatography. The eluent has also been chosen so that the different compounds can be separated effectively. The eluent is optimized in small scale pretests, often using thin layer chromatography (TLC) with the same stationary phase.
    There is an optimum flow rate for each particular separation. A faster flow rate of the eluent minimizes the time required to run a column and thereby minimizes diffusion, resulting in a better separation. However, the maximum flow rate is limited because a finite time is required for analyte to equilibrate between stationary phase and mobile phase, see Van Deemter's equation. A simple laboratory column runs by gravity flow. The flow rate of such a column can be increased by extending the fresh eluent filled column above the top of the stationary phase or decreased by the tap controls. Faster flow rates can be achieved by using a pump or by using compressed gas (e.g. air,nitrogen, or argon) to push the solvent through the column (flash column chromatography).
    The particle size of the stationary phase is generally finer in flash column chromatography than in gravity column chromatography. For example, one of the most widely used silica gel grades in the former technique is mesh 230 – 400 (40 – 63 µm), while the latter technique typically requires mesh 70 – 230 (63 – 200 µm) silica gel.

    A spreadsheet that assists in the successful development of flash columns has been developed. The spreadsheet estimates the retention volume and band volume of analytes, the fraction numbers expected to contain each analyte, and the resolution between adjacent peaks. This information allows users to select optimal parameters for preparative-scale separations before the flash column itself is attempted.

    An automated ion chromatography system.

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    Typical set up for manual column chromatography





    Tuesday, 23 July 2013

    Nano-Technoloogy Makes Medicine Greener

    The ultra small nanoreactors have walls made of lipids. During their fusion events volumes of one billionth of a billionth of a liter were transferred between nanoreactors allowing their cargos to mix and react chemically. We typically carried out a million of individual chemical reactions per cm2 in not more than a few minutes. (Credit: Image courtesy of University of Copenhagen)http://www.sciencedaily.com/releases/2011/11/111103132357.htm
     Researchers at the University of Copenhagen are behind the development of a new method that will make it possible to develop drugs faster and greener. Their work promises cheaper medicine for consumers.
    Over the last 5 years the Bionano Group at the Nano-Science Center and the Department of Neuroscience and Pharmacology at the University of Copenhagen has been working hard to characterise and test how molecules react, combine together and form larger molecules, which can be used in the development of new medicine.http://www.sciencedaily.com/releases/2011/11/111103132357.htm

    Sunday, 21 July 2013

    The first total synthesis of fuscain

    First total synthesis of fuscain

    First total synthesis of fuscain

    Fuscain is a new furanolactam isolated from the sponge Phacellis fusca from the South China Sea. Furan analogues isolated from marine organisms have valuable medicinal properties. The first total synthesis of fuscain is reported in Journal of Chemical Research December issue. The key step in the synthesis is the formation of seven-membered lactam by acylation of a furan ring using the mild Lewis acid CuSO4•5H2O.
    Fuscain, a new furanolactam which was originally isolated from the sponge Phacellis fusca collected in South China Sea, showed a moderate cytotoxicity toward P388 and L1210 cell lines. The same sponge yielded three pyrrololactam alkaloids: saldisin, 2-bromoaldisin and debromohymenialdisin.2 Recently, furan analogues isolated from marine organisms have shown anticancer,3–5 antibacterial,6 anticoagulant, antifungal, antimalarial,  antiplatelet, antituberculosis and antiviral activities11. Aldisin-based derivatives can be easily synthesised. However, it is still a challenge to synthesise fuscain. Hence the biological effects of fuscain and its derivatives on cell cycle progression and antitumour activities have rarely been reported. The synthetic route to fuscain is shown below.
    The key step is an intramolecular Friedel–Crafts cyclisation to form the seven-membered ring. Various Lewis acids (polyphosphoric acid, POCl3, polyphosphoric acid–acetic acid, POCl3–P2O5, TFA or MSA) have been reported for Friedel– Crafts cyclisation.13,14. Initially, we selected PPA and P2O5 as catalysts but no product was obtained. Because of the structural difference between Alidisin and fuscain, the aromaticity of furan ring is less than a pyrrole ring, and a furan ring usually polymerised under acidic conditions, we selected a relatively mild Lewis acid CuSO4•5H2O to complete the intramolecular cyclisation to form fuscain.

    Source: Journal of Chemical Research, Volume 36, Number 12, December 2012 , pp. 736-737(2)
    doi: 10.3184/174751912X13528167435099
    Yuan-wei Liang, Xiao-jian Liao, Chang-jun Wang, Jin-zhi Guo, Shuo Li and Shi-hai Xu*
    Department of Chemistry, Jinan University, Guangzhou 510632, P. R. China