130791-77-4

Basic information

• Product Name: (+)-huperzine A
• Synonyms: (+)-huperzine A
• CAS NO: 130791-77-4
• Molecular Weight: 242.321
• Mol File: 130791-77-4.mol

Chemical Properties

• CAS DataBase Reference: (+)-huperzine A(CAS DataBase Reference)
• NIST Chemistry Reference: (+)-huperzine A(130791-77-4)
• EPA Substance Registry System: (+)-huperzine A(130791-77-4)

Safety Data

• Hazardous Substances Data: 130791-77-4(Hazardous Substances Data)

Upstream product

• 120686-04-6 (1S,9S)-13-Eth-(E)-ylidene-5-methoxy-11-methyl-6-aza-tricyclo[7.3.1.0^2,7]trideca-2⁽⁷⁾,3,5,10-tetraene-1-carboxylic acid 
• 185741-46-2 methyl ((5S,E)-11-ethylidene-2-methoxy-7-methyl-5,6,9,10-tetrahydro-5,9-methanocycloocta[b]pyridin-5-yl)carbamate 
• 185741-42-8 (1S,9R)-10-Methanesulfonyloxy-5-methoxy-11-methyl-13-oxo-6-aza-tricyclo[7.3.1.0^2,7]trideca-2⁽⁷⁾,3,5-triene-1-carboxylic acid methyl ester 
• 955117-18-7 (5R,9R,11E)-5-(3-phenylprop-2-en-1-ylideneamino)-11-ethylidene-5,6,9,10-tetrahydro-7-methyl-5,9-methanocycloocta[b]pyridin-2(1H)-one 
• 120786-18-7 (+/-)-huperzine 
• 4746-97-8 cyclohexanedione monoethylene ketal 
• 52506-21-5 8-oxo-1,4-dioxa-spiro[4.5]decane-7-carboxylic acid methyl ester 
• 120686-05-7 (E)-(+/-)-(11-ethylidene-9,10-dihydro-2-methoxy-7-methyl-5,9-methanocyclooctapyridin-5(6H)-yl)carbamic acid methyl ester 
• 120786-17-6 (E)-(+/-)-11-ethylidene-9,10-dihydro-2-methoxy-7-methyl-5,9-methanocyclooctapyridine-5(6H)-carboxylic acid methyl ester 
• 123436-02-2 [(1R,9R)-13-Eth-(E)-ylidene-5-methoxy-11-methyl-6-aza-tricyclo[7.3.1.0^2,7]trideca-2⁽⁷⁾,3,5,10-tetraen-1-yl]-carbamic acid ethyl ester 

Downstream Products

• 3279-76-3 6-methyl-2(1H)-pyridone 
• 957115-16-1 O,N-bis(phenoxycarbonyl)huperzine A 
• 64407-57-4 N,N-dicyclohexylurea 
• 923272-87-1 (5R,9R,11E)-5-(4-hydroxy-3-methoxyphenylmethylidenylamino)-11-ethylidene-5,6,9,10-tetrahydro-7-methyl-5,9-methanocycloocta[b]pyridin-2(1H)-one 
• 955117-18-7 (5R,9R,11E)-5-(3-phenylprop-2-en-1-ylideneamino)-11-ethylidene-5,6,9,10-tetrahydro-7-methyl-5,9-methanocycloocta[b]pyridin-2(1H)-one 
• 956291-33-1 C₂₄H₂₆N₂O₃ 
• 956291-35-3 C₂₄H₂₆N₂O₃ 
• 923272-94-0 (5R,9R,11E)-5-(4-methoxyphenylmethylidenylamino)-11-ethylidene-5,6,9,10-tetrahydro-7-methyl-5,9-methanocycloocta[b]pyridin-2(1H)-one 
• 1004513-05-6 (5R,9R,11E)-5-(2-methyl-3-phenylprop-2-en-1-ylideneamino)-11-ethylidene-5,6,9,10-tetrahydro-7-methyl-5,9-methanocycloocta[b]pyridin-2(1H)-one 
• 953425-69-9 C₂₈H₃₂N₂O₇ 
• 956291-37-5 C₂₃H₂₁N₃O 
• 956291-32-0 C₂₄H₂₇N₃O 
• 956291-36-4 C₂₄H₂₆N₂O₃ 
• 1004513-26-1 C₂₆H₂₉N₃O 

Relevant articles and documents

Synthetic method of huperzine A

The invention belongs to the technical field of medicine synthesis and particularly relates to a synthetic method of huperzine A. The method includes twelve steps of reactions, 1,4-dioxaspiro[4.5]decan-8-one being a raw material, so that the chemical synthesis of the huperzine A is completed at a high total yield. The method is fewer in reaction steps, is simple in operations, has high yield, is stable in intermediates and gentle in reaction conditions, and is easy to control in reactions.

METHODS OF RESOLVING RACEMIC MIXTURE TO OBTAIN (-)-HUPERZINE A

A method of resolving a racemic mixture of (±) Huperzine A to (-)-Huperzine A includes: separating the (-)-Huperzine A from the racemic mixture of (±) Huperzine A by chiral high performance liquid chromatography (HPLC), the chiral HPLC being performed utilizing a mobile phase including a solution including an alcohol and one selected from dichloromethane, trichloromethane, and a mixture thereof, and the chiral HPLC being performed utilizing a chiral stationary phase including a polysaccharide derivative.

PREPARATION OF (-)-HUPERZINE A

The present invention relates to a method for preparing (?)-huperzine A. The method involves: allowing a mixture of (±)-huperzine A obtained from chemical synthesis and a chiral acid to form (±)-huperzine A chiral acid salt under suitable conditions; recrystallizing the chiral acid salt from an organic solvent and basifying with an alkali to obtain optically pure (?)-huperzine A. The method is convenient to operate and suitable for industrial production. The chemical purity and optical purity of (?)-huperzine A obtained by the method are each greater than 99.5%, satisfying the requirement for raw pharmaceutical purity in the pharmaceutical industry.

Cyclobutane Synthesis and Fragmentation. A Cascade Route to the Lycopodium Alkaloid (-)-Huperzine A

An asymmetric total synthesis of the nootropic alkaloid (-)-huperzine A was completed using a cascade sequence initiated by an intramolecular aza-Prins reaction and terminated by a stereoelectronically guided fragmentation of a cyclobutylcarbinyl cation as the key step in assembling the bicyclo[3.3.1]nonene core of the natural product. Intramolecular [2 + 2]-photocycloaddition of the crotyl ether of (S)-4-hydroxycyclohex-2-enone afforded a bicyclo[4.2.0]octanone containing an embedded tetrahydrofuran in which the cyclohexanone moiety was converted to a triisopropylsilyl enol ether and functionalized as an allylic azide. The derived primary amine was acylated with α-phenylselenylacrylic acid, and the resulting amide was reacted with trimethylaluminum to give a [2 + 2]-cycloadduct, which underwent retroaldol fission to produce a fused α-phenylselenyl δ-lactam. Periodate oxidation of this lactam led directly to an α-pyridone, which was converted to a fused 2-methoxypyridine. Reductive cleavage of the activated "pyridylic" C-O bond in this tetracycle and elaboration of the resultant hydroxy ketone to a diketone was followed by chemoselective conversion of the methyl ketone in this structure to an endo isopropenyl group. Condensation of the remaining ketone with methyl carbamate in the presence of acid initiated the programmed cascade sequence and furnished a known synthetic precursor to huperzine A. Subsequent demethylation of the carbamate and the methoxypyridine, accompanied by in situ decarboxylation of the intermediate carbamic acid, gave (-)-huperzine A.

An efficient total synthesis of (-)-huperzine A

The total synthesis of Lycopodium alkaloid (-)-huperzine A has been accomplished in 10 steps with 17% overall yield from commercially abundant (R)-pulegone. The synthetic route features an efficient synthesis of 4 via a Buchwald-Hartwig coupling reaction,

(--)- HUPERZINE A PROCESSES AND RELATED COMPOSITIONS AND METHODS OF TREATMENT

The invention provides (1) processes for making substantially-pure (-) huperzine A and substantially-pure (-) huperzine A derivatives; (2) compositions useful in making substantially-pure (-) huperzine A and substantially-pure (-) huperzine A derivatives; and (3) methods of treating or preventing neurological disorders using substantially-pure (-) huperzine A and substantially-pure (-) huperzine A derivatives.

DERIVATIVES OF 5,9-METHANOCYCLOOCTA[B]PYRIDIN-2-(1H)-ONE, THEIR PREPARATION AND USE AS ANALGESICS

A compound of Formula I, a pharmaceutically-acceptable salt or a hydrate thereof, wherein R1 is H, or C1-4 alkyl; R2 is H, halogen, or C1, alkyl; R3 is H, halogen, or C1-4 alkyl, and R4 is C1-6 alkyl, aryl; or ═CR3R4 is cyclopentylidene, cyclohexylidene, 1-methylpiperidin-4-ylidene, or inden-1-ylidene; R5 is independently at each occurrence F, Cl, Br, CF3, R9, OR9, NR9R10, NO2, CN, COOR9, O2CR9, CONR9R10, NR9C(O)R10, heterocyclic group, aryl, or a group of Formula II; R6 is H, halogen, or C1-4 alkyl; R7 is H, halogen, or C1-4 alkyl; R8 is H, C1, alkyl group; R9 is H, or C1-6 alkyl; R10 is H, or C1-6 alkyl; R11 is H, or C1-4 alkyl; R12 is H, or C1-4 alkyl; m is 0, 1, or 2; when R5 is F, Cl, Br, CF3, R9, OR9, NR9R10, NO2, CN, COOR9, O2CR9, CONR9R10, NR9C(O)R10, heterocyclic group, or aryl, n is 1, 2, 3, or 4; when R5 is the group of Formula II, n is 0, 1, 2, 3, or 4; x is 0, 1, 2, 3, or 4.

Total synthesis of (-)-huperzine A

The total synthesis of (-)-huperzine A was accomplished in 23 steps from a commercially available anhydride. Our synthetic route features a facile construction of the bicyclo[3.3.1] skeleton equipped with proper functionalities to introduce the remaining substructures.

METHOD OF PREPARING HUPERZINE A AND DERIVATIVES THEREOF

The present invention is related to the synthesis of huperzine A. The synthesis includes a variety of process steps that increase productivity, reduce safety concerns, and allow for increasing production of compounds of desired optical isomer. The inventive methods may encompass a single improved reaction step that may be incorporated into a known reaction process for synthesizing huperzine A or a derivative thereof to improve the overall reaction. The inventive methods also encompass complete synthesis methods for preparing huperzine A or a derivative thereof.

Racemic huperzine A

The present invention relates to racemic huperzine A, a pharmaceutical composition comprising huperzine A, its use as a medicament and for the manufacture of a medicament for the inhibition of the cholesterase enzymes in a mammal.