132435-40-6Relevant articles and documents
Synthetic studies of huperzine A and its fluorinated analogues. 1. Novel asymmetric syntheses of an enantiomeric pair of huperzine A
Kaneko, Satoru,Yoshino, Toshiharu,Katoh, Tadashi,Terashima, Shiro
, p. 5471 - 5484 (1998)
Syntheses of an enantiomeric pair of huperzine A were accomplished by employing two types of methods which feature the tandem Cinchona alkaloids- promoted asymmetric Michael addition / aldol reaction of the β-keto ester 3 with methacrolein (4) (max. 64% ee, 3+4 → 5, Scheme 2) and the asymmetric bicycloannulation of 3 with 2-methylene-1,3-propanediol diocetate (7) catalyzed by palladium catalysts carrying chiral ferrocenylphosphine ligands (max. 64% ee, 3+7 → 8, Scheme 3) as the key steps. Recrystallization of the partially optically active tricycles (+)- and (-)-6 derived from the products of the asymmetric reactions, readily provided the corresponding optically pure samples (both >99% ee). According to the reported method, the total synthesis of an enantiomeric pair of 1 [(-)- and (+)-1] was completed starting with optically pure (+)- and (-)-6 (Scheme 4).
PREPARATION OF (-)-HUPERZINE A
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Paragraph 0128; 0129, (2016/06/28)
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
White, James D.,Li, Yang,Kim, Jungchul,Terinek, Miroslav
, p. 11806 - 11817 (2015/12/11)
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.
