- PHARMACEUTICAL COMPOSITION FOR USE IN MEDICAL AND VETERINARY OPHTHALMOLOGY
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The invention relates to pharmaceutics, medicine, in particular to manufacturing and use of pharmaceutical compositions of medicines (ophthalmic preparations) comprising mitochondria-addressed antioxidant and a set of auxiliary substances providing effective treatment for ophtalmological diseases in humans and animals.
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- A practical and scaleable total synthesis of the jaborandi alkaloid (+)-pilocarpine
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The total synthesis of (+)-pilocarpine (as its nitrate salt) has been achieved in nine steps and 30% overall yield starting from racemic 2-(2′,2′-dimethoxyethyl)propane-1,3-diol, which was desymmetrised via an enzymatic protocol. A high yielding synthesis of a key α-ethylidene lactone precursor has been developed, which involves the palladium-catalysed decarboxylation/carbonylation of a 1,3-dioxan-2-one for formation of the γ-butyrolactone ring. Subsequent hydrogenation of the α-ethylidene lactone introduces the C(3)-stereochemistry to give a 72:28 mixture of (+)-pilocarpine and (+)-isopilocarpine, which are readily separable via recrystallisation of the (+)-pilocarpine nitrate salt.
- Davies, Stephen G.,Roberts, Paul M.,Stephenson, Peter T.,Storr, Helen R.,Thomson, James E.
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experimental part
p. 8283 - 8296
(2009/12/28)
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- Synthesis of optically active lactones from L-aspartic acid and intermediates thereof
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Optically active lactones are described, such as an intermediate lactone having the formula STR1 where R and R2 are each independently alkyl with 1 to 6 carbon atoms, cycloalkyl with 6 to 10 carbon atoms, aryl with 6 to 10 carbon atoms, or arylalkyl with 7 to 19 carbon atoms, R4 is H or C1-6 alkyl, and Ar is a homo- or heteroaromatic ring with 5 or 6 ring atoms being optionally substituted by C1-6 alkyl or alkoxy groups, halogen atoms, cyano or nitro groups. Such optically active, intermediate lactones are prepared from L-aspartic acid, and can be readily converted to (+)-pilocarpine and its analogues by hydrolysis, reduction, and hydrogenation, such as to an optically active lactone having the formula STR2 which is (+)-pilocarpine when R is ethyl, R4 is H, and Ar is 1-methylimidazol-5-yl.
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- An Effective Chirospecific Synthesis of (+)-Pilocarpine from L-Aspartic Acid
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A short and efficient synthesis of (+)-pilocarpine (1) has been accomplished in 10 steps and 51percent overall yield from L-aspartic acid.The synthesis features a diastereoselective alkylation of a protected aspartic acid diester derivative and a selective hydrolysis of the α-methyl ester to give the corresponding amino acid.Subsequent replacement of the amino group with bromo, esterification, and a modified Reformatsky reaction with 1-methylimidazole-5-carboxaldehyde (8) afforded imidazole-substituted lactone 28.Details concerning this novel lactone synthesis are also described.Finally, hydrogenolysis of the lactone carbon-oxygen bond and selective reduction of the resulting monoester afforded pure (+)-pilocarpine (1).
- Dener, Jeffrey M.,Zhang, Lin-Hua,Rapoport, Henry
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p. 1159 - 1166
(2007/10/02)
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- Sustained-release formulation containing an amino acid polymer with a lower alkyl (C1 -C4) polar solvent
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A sustained-release polymeric hydrogel dosage form useful for topical, systemic or transdermal administration of a medicinal agent comprising a cross-linked, polymerized hydrophilic polymer, an amino acid polymer, a cross-linking agent, and an optional hydrophobic monomer and/or a chain regulator in conjunction with a lower alkyl (C1 -C4), polar solvent and said medicinal agent in a therapeutically effective amount.
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