Galantamine chemical structure Scheme 1. Trost 2005 Galanthamine total synthesis:a bromine, sodium acetate, acetic acid, iron, rt b potassium carbonate, 2days c  Troc-Cl, DMAP, Pyridine, dichloromethane d palladium,Trost ligand, triethylamine, dichloromethane e 1.5 mol % TsOH, CH(OMe)3, methanol f DIBAL-H, toluene, -78 °C, 1 hr g  triphenylphosphine, acetonecyanohydrin, DIAD, diethyl ether h 2.20 mol % TsOH, THF, water i  15 mol % Palladium(II) acetate, 15 mol% dppp, 3 eq. Ag2CO3, toluene, 107 °C j selenium dioxide  disodium hydrogen phosphate dioxane, 150 °C 3 hrs k  methylamine ,methanol l 4 eq. DIBAL-H, m aqueous NaH2PO4 n NaCNBH3
Find information on thousands of medical conditions and prescription drugs.

Galantamine

Galantamine (trade name Razadyne®, Reminyl®) is a medication used in the treatment of Alzheimer's disease. more...

Home
Diseases
Medicines
A
B
C
D
E
F
G
Gabapentin
Gabitril
Galantamine
Gamma-hydroxybutyrate
Ganciclovir
Garamycin
Gaviscon
Gemcitabine
Gemfibrozil
Gemhexal
Gemzar
Generlac
Gentamicin
Geodon
Gleevec
Gliadel
Gliadel Wafer
Glibenclamide
Glimepiride
Glipizide
Glucagon
Glucobay
Glucohexal
Glucophage
Glucosamine
Glucotrol
Glutethimide
Golytely
Gonadorelin
Goserelin
Gramicidin
Gramicidin S
Granisetron
Grifulvin V
Griseofulvin
Guaifenesin
H
I
J
K
L
M
N
O
P
Q
R
S
T
U
V
W
X
Y
Z

Galantamine is mostly used as hydrobromide salt. It is a centrally acting reversible cholinesterase inhibitor in the same class as donepezil. Galantamine has a much shorter half life than donepezil (there is a newer prolonged release version available in 2004) and it also has more nicotinic receptor activity and is potentially more stimulating but also probably because of this activity tends to cause worse gastrointestinal side effects.

Total synthesis

The natural source of galantamine are certain species of daffodil and because these species are scarce and because the isolation of galanthamine from daffodil is expensive (a 1996 figure specifies 50,000 US dollar per kilogram) alternative synthetic sources are under development by means of total synthesis. One recent publication details the enantioselective organic synthesis of galanthamine and also that of morphine from a single precursor .

The total synthesis of galanthamine (Trost 2005) is described as follows (see scheme 1): the sequence starts by bromination by electrophilic aromatic substitution of isovanillin 1 to bromophenol 2, then by synthesis of the second intermediate 5 by reacting dialdehyde 3 in a coupled aldol reaction and Horner-Wadsworth-Emmons reaction with trimethyl phosphonoacetate 4. The hydroxyl group is activated as a leaving group by acetylation with trichloroethyl carbonate (Troc) to 6. Next an enantioselective Trost AAA reaction takes place between bromophenol 2 and carbonate 6 to the allyl ether 7. Next the aldehyde group is protected as an acetal in 8 and this step enables the to organic reduction of the ester group to the alcohol 9 with DIBAH and subsequent conversion of this alcohol to a nitrile by nucleophilic displacement to 10 followed by aldehyde deprotection to 11. The intramolecular Heck reaction to 12 creates the dihydrofuran ring. Allylic oxidation by selenium dioxide provides allylic alcohol 13 with the correct stereochemistry. The aldehyde reacts with methylamine to the imine 14 and reduction of the imine and nitrile by DIBAL-H leading to ring-closure to the hemi-aminal 15 (not isolated) followed by acid quenching gives the alcohol 16. In the final step this alcohol group is reduced to give Galanthamine 17 together with 6% of the epi isomer 18.

Read more at Wikipedia.org


[List your site here Free!]


Use of benzodiazepines and fractures in older persons
From American Family Physician, 5/15/05 by Karl E. Miller

Benzodiazepines are the 13th leading prescription medication in the United States. This drug class has had an annual growth rate of 3 percent despite concerns about the adverse effects of these medications. One main concern is the increased risk for hip fractures in older patients receiving benzodiazepines. Findings from studies of this issue are inconsistent, with some suggesting that long-acting benzodiazepines carry a greater risk for falls and hip fractures in older persons. Other studies have found that the highest risk for falls in older patients is during the first two weeks of benzodiazepine use, but follow-up after the first two weeks was inconsistent in establishing risk of falls. Because this class of medication provides benefits in the treatment of anxiety and agitation, physicians need to know the risk of falls and hip fracture in older patients before initiating these medications. Wagner and colleagues assessed the risk for hip fracture and benzodiazepine use in older patients.

The study was performed using the database from New Jersey's Medicaid program. All persons enrolled in the program between January 1987 and June 1990 were included in the study if they were 65 years or older. Data were collected on these persons until they were admitted to the hospital for hip fracture or withdrawn because of death or loss of Medicaid eligibility. The study duration was 42 months. Information on medication use was collected from the same database. The benzodiazepine use was categorized into long-acting, short-acting, low-potency, and high-potency. All dosages of benzodiazepines were converted to the diazepam milligram equivalent based on a previously validated equivalency study. In addition, information concerning previous and current medication dispensing and diagnosis information was included in the database. The diagnosis of hip fracture was established based on hospital claims with the primary discharge diagnosis of hip fracture.

There were 125,203 persons (194,071 person-years) included in the data analysis. In that group, 2,312 hip fractures met the inclusion criteria. When controlling for multiple factors in the analysis, hip fractures were significantly higher in patients exposed to benzodiazepines compared with those who had no such exposure. The patients receiving short-acting, high-potency benzodiazepines had a risk for hip fractures similar to that of patients receiving long-acting benzodiazepines. The risk for hip fracture was highest during the first two weeks of benzodiazepine use and declined over time.

The authors conclude that the incidence of hip fracture in older patients seems to be related to the use of benzodiazepines. The risk for hip fracture is no different when comparing short-acting with long-acting benzodiazepines. The highest risk for hip fracture is within the first two weeks of exposure to benzodiazepines.

Wagner AK, et al. Benzodiazepine use and hip fractures in the elderly. Who is at greatest risk? Arch Intern Med July 26, 2004;164:1567-72.

COPYRIGHT 2005 American Academy of Family Physicians
COPYRIGHT 2005 Gale Group

Return to Galantamine
Home Contact Resources Exchange Links ebay