Organic compounds -- part of the class 532-570 series – Organic compounds – Cyclopentanohydrophenanthrene ring system containing
Reexamination Certificate
1999-08-10
2002-05-21
Carr, Deborah (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Cyclopentanohydrophenanthrene ring system containing
C552S540000, C552S544000, C554S012000, C554S016000
Reexamination Certificate
active
06392070
ABSTRACT:
BACKGROUND OF THE INVENTION
Birch bark is a low-value waste product in the forest industry today. Ekman, R.,
Holzforschung,
(1983) 37, 205. Approximately 230,000 tons of birch bark are generated per year. For example, a single paper mill can generate 70 tons of birch bark per day. Thus, vast quantities of birch bark and its chemical components are available.
Birch bark is a potential source of a variety of organic chemicals. Several triterpenoids have been identified in birch bark extracts. For example, lupeol, betulin, betulinic aldehyde, betulinic acid, methyl betulinate, lupenone, betulonic aldehyde, betulonic acid, &bgr;-amyrin, erythrodiol, oleanolic aldehyde, oleanolic acid, methyl leanolate and acetyl oleanolic acid are all present in the outer bark of
Betula verrucosa.
Eckerman, C., (1985)
Paperi ja Puu,
No. 3, 100. In addition, several suberinic acids isolated from birch bark, as well as several triterpenoids, have been identified in the bark of
Betula verrucosa.
Ekman, R.,
Holzforschng,
(1983) 37, 205.
The chemical constituents of birch bark are useful in pharmaceutical and industrial applications. For example, U.S. Pat. No. 5,750,578 discloses that betulin possesses antiviral properties and is useful to treat herpesvirus. Betulin also possesses antifeedant activity against boll weevils, and anti-inflammatory activity (Miles, D. H., 1994,
J. Agric. Food. Chem.,
42, 1561-1562 and Recio, M.,
Planta Med.,
1995, 61, 9-12. In addition, betulin showed cough suppressant and expectorant effects. Jinuhua, W.,
Zhongguo Yaoxue Zazhi,
(1994), 29(5), 268-71. Betulin is also a useful starting material for preparing alobetulin and derivatives thereof, which posses useful pharmacological properties.
Betulin can be converted to betulinic acid, which is useful as a therapeutic agent. For example, Pisha, E. et al., (1995)
J. M. Nature Medicine,
1, 1046-1051 discloses that betulinic acid has antitumor activity against human melanoma, e.g., MEL-1, MEL-2 and MEL-4. In addition, Fujioka, T. et al.,
J. Nat. Prod.,
(1994) 57, 243-247 discloses that betulinic acid has anti-HIV activity in H9 lymphocytic cells.
Ambrettolide (cis-hexadec-7-enolide), a naturally occurring compound, is used to induce musk fragrance in perfumes. Ambrettolide is found in the vegetable oil of ambrette seeds. The synthesis of ambrettolide is accomplished from 9,10,18-trihydroxyoctadecanoic acid via a high-yielding multi-step synthesis. Seoane, E.,
J. Chem. Soc. Perkin Trans.
(1982), 1837-1839. Therefore, 9,10,18-trihydroxyoctadecanoic acid, which is present in birch bark, is a useful precursor for the synthesis of ambrettolide.
9,10-Epoxy-1 8-hydroxyoctadecanoic acid is also present in birch bark. 9,10-Epoxy-18-hydroxyoctadecanoic acid is an environmentally-friendly spoilage deterrent and a rot-resistant additive for wood composites. Sweitzer, P., et al., Induction of Resistance in Barley Against
Erysiphe graminis
by Free Cutin Monomers,
Physiol. Mol. Plant Pathol,
(1996) 49(2) 103-120.
Suberin is another major component of birch bark. Suberin is an insoluble polymeric material that is attached to the cell walls of periderms. Kola, P. E. et al.,
Ann. Rev. Plant. Physiol.,
(1981), 32: 539-67. Suberin is generally an ester of fatty acids and polyphenolic polymers. Suberin of birch bark is typically a biopolyester of primary hydroxy, epoxy and dicarboxylic acids. Ekman,
Holzforschung,
(1983) 37, 205-211.
Suberin posseses several industrial applications. See, e.g., Taylor and Francis,
Forests Products Biotechnology,
A. Bruce and J. W. Palfreyman (editors), 167, 179-181 (199); Peter E. Laks and Peggy A. McKaig,
Flavonoid Biocides: Wood Preservatives Based on Condensed Tannins, Horzfschung,
42, 299-306 (1988); Etherington & Roberts, Dictionary—birch(bark), http://sul-server2.stanford.edu/don/dt/dt0328.html, 1, Jun. 23, 1999; P. E. Kolattukudy, Structure, Biosynthesis, and Biodegradation of Cutin and Suberin,
Ann. Rev. Plant Physiol.,
32, 539-67 (1981); and N. Cordeiro, M. N. Belgasem, A. J. D. Silvestre, C. Pascol Neto, A. Gandini, Cork Suberin as a new source of chemicals,
Int. Journal of Biological Materials,
22, 71080 (1998). Suberin is useful as a dispersant in many industrial applications (e.g., carbon black slurries, clay products, dyes, cement, oil drilling muds, and asphalt emulsifiers). Suberin is also useful in binders for animal pellets, conditioners for boiling water, anti-oxidants and additives to lead-storage battery plate expanders. McGraw-Hill Concise Encyclopedia of Science & Technology, Fourth Edition, 1998.
Polyphenolic polymers are also present in birch bark as a constituent of suberin. Polyphenolic polymers may be classified as soluble polyphenolic polymers or non-soluble polyphenolic polymers. Soluble polyphenolic polymers are the portion of polymers which are soluble in water under both acidic and basic conditions. The non-soluble polyphenolic polymers are non-soluble in water at a pH below about 4.0, but soluble in acetone, alcohols and other polar solvents. The non-soluble polyphenolic polymers may have a different formulation from the soluble polyphenolic polymers. However, the non-soluble polyphenolic polymers may be used in the same industrial applications as the soluble polyphenolic polymers.
Polyphenolic polymers are non-toxic and biodegradable and may be formulated for numerous purposes (e.g., as anti-oxidant reagents, anti-fungal materials, coating materials, co-polymers, wood preservatives, tire cord adhesives, foundry cord binders, rigid and floral foams, ion exchange resins, industrial water purification flocculants, textile dyes, food additives and pharmaceuticals). Pizzi,
Wood Bark Extracts as Adhesives and Preservatives,
167-181, Taylor & Frances,
Forest Products Biotechnology,
Bruce and Palfreyman (editors), 1998.
Current methods for isolating the chemical constituents of birch bark are deficient in several ways. For example, betulin has been extracted from the bark of white-barked birches in amounts up to 30%, based on the dry weight of the bark. Elkman, R., (1983)
Holzforsch,
37, 205; Ohara, S., et al., (1986)
Mokuza Gakkaishi,
32, 266. In addition, Betulin has been isolated from outer birch bark waste of
Betula verrucosa
by liquid extraction employing boiling organic solvents and subsequent recrystallization. Eckerman, C., (1985)
Paperi ja Puu,
No. 3, 100. While current processes afford acceptable yields of betulin (e.g., 11-30%), these processes suffer from several major drawbacks. For example, the use of a boiling organic solvent, at standard pressure, in the extraction of betulin may destroy other useful compounds present in the bark. A need therefore exists for a method that can be used to extract betulin without damaging other compounds remaining in the birch bark.
Another drawback with the current extraction processes is that the organic solvents employed are hazardous, difficult to handle or difficult to dispose of. The typical organic solvents, which include methylene chloride and chloroform, are hazardous to humans (i.e., they are toxic or carcinogenic) and are hazardous to the environment. Considering the industrial scale on which the extraction processes would need to be performed in order to provide industrial quantities (e.g., tons) of betulin, large quantities of organic solvents would be required. The high cost of disposing the organic solvents is an additional disadvantage of the current extraction procedures.
Several methods have been devised for isolating polyphenolic polymers from birch trees. Some isolation methods are based on acid treatments in which the carbohydrate components (cellulose and hemicelluloses) are hydrolyzed to water-soluble materials. However, with such procedures, serious doubts exist as to whether the isolated polyphenolic polymer is representative of the “native” polyphenolic polymer. In addition, extraction conditions can cause undesirable rearrangements and other transformations of the polyphenolic structure that lead to a loss of useful properties. It is therefore desirable to have polyph
Carlson Robert M.
Krasutsky Pavel A.
Nesterenko Vitaliy V.
Carr Deborah
Regents of the University of Minnesota
Schwegman Lundberg Woessner & Kluth P.A.
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