2688-77-9

Usage

Uses

Used in Pharmaceutical Industry:
Laudanosine is used as a metabolite in the development and study of neuromuscular-blocking drugs for [application reason] its ability to cross the blood-brain barrier and its potential toxic systemic effects, which can be significant in understanding the drug's mechanism and side effects.
Used in Research and Development:
Laudanosine is used as a research compound for [application reason] its ability to cross the blood-brain barrier, which makes it a valuable tool in studying the effects of various substances on the central nervous system and their potential for causing excitement and seizure activity.
Used in Toxicology Studies:
Laudanosine is used as a subject in toxicology studies for [application reason] its potentially toxic systemic effects, which can help in understanding the safety profiles and risks associated with the use of neuromuscular-blocking drugs in medical treatments.

InChI:InChI=1/C21H27NO4/c1-22-9-8-15-12-20(25-4)21(26-5)13-16(15)17(22)10-14-6-7-18(23-2)19(11-14)24-3/h6-7,11-13,17H,8-10H2,1-5H3/t17-/m0/s1

Upstream product

• 1699-51-0 laudanosine 
• 106647-99-8 (+)-threo-N-(ethoxycarbonyl)hydroxynorlaudanosine 
• 186581-53-3 diazomethane 
• 77-95-2 1,3,4,5-tetrahydroxy-cyclohexanecarboxylic acid 
• 408331-39-5 6,7-dimethoxy-1-(3,4-dimethoxybenzyl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-ol 
• 91-16-7 1,2-dimethoxybenzene 
• 54881-16-2 (S)-6-Benzyloxy-1-(3,4-dimethoxy-benzyl)-7-methoxy-1,2,3,4-tetrahydro-isoquinoline 
• 7306-46-9 4-chloromethyl-1,2-dimethoxy-benzene 
• 21852-32-4 4-bromomethyl-1,2-dimethoxybenzene 
• 1210-57-7 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-1-carbonitrile 
• 1449213-93-7 (E)-2-(2-(3,4-dimethoxystyryl)-4,5-dimethoxyphenyl)ethanamine 
• 1449213-92-6 (E)-4-(4,5-dimethoxy-2-((E)-2-nitrovinyl)styryl)-1,2-dimethoxybenzene 
• 1449213-91-5 (E)-2-(3,4-dimethoxystyryl)-4,5-dimethoxybenzaldehyde 
• 6380-23-0 3,4-dimethoxystyrene 

Downstream Products

• 475-81-0 glaucine 
• 120-14-9 3,4-dimethoxy-benzaldehyde 
• 26952-97-6 2,3,6,7-tetramethoxy-9,10-dihydro-anthracene 
• 1699-51-0 laudanosine 
• 23669-24-1 (+/-)-N-ethyl-Laudanosine iodide 
• 85-63-2 (R)-laudanosine 

Relevant academic research and scientific papers

Asymmetric total synthesis of (?)-javaberine A and (?)-epi-javaberine A based on catalytic intramolecular hydroamination of N-methyl-2-(2-styrylaryl)ethylamine

Asymmetric total synthesis of (?)-javaberine A and its epimer was achieved by utilizing two methods for isoquinoline synthesis, asymmetric hydroamination of N-methyl-2-(2-styrylaryl)ethylamine and Bischler-Napieralski cyclization. Intramolecular asymmetric hydroamination of N-methyl aminoalkene 4 was catalyzed by lithium amide–chiral bisoxazoline to give tetrahydroisoquinoline (S)-laudanosine with good enantioselectivity in excellent yield. N-Demethylation of (S)-laudanosine was accomplished by Polonovski-type reaction to give (S)-norlaudanosine. Condensation of (S)-norlaudanosine with homoveratric acid, and subsequent Bischler-Napieralski cyclization, LiAlH4 reduction, and O-demethylation furnished (8R,14S)-(?)-javaberine A, corresponding to antipode of natural javaberine A. (8S,14S)-(?)-Javaberine A, which corresponds to C14-epimer of natural javaberine A, was also successfully synthesized.

Organocatalytic Enantioselective Pictet-Spengler Approach to Biologically Relevant 1-Benzyl-1,2,3,4-Tetrahydroisoquinoline Alkaloids

(Figure Presented) A general procedure for the synthesis of 1-benzyl-1,2,3,4-tetrahydroisoquinolines was developed, based on organocatalytic, regio- and enantioselective Pictet-Spengler reactions (86-92% ee) of N-(o-nitrophenylsulfenyl)-2-arylethylamines with arylacetaldehydes. The presence of the o-nitrophenylsulfenyl group, together with the MOM-protection in the catechol part of the tetrahydroisoquinoline ring system, appeared to be a productive combination. To demonstrate the versatility of this approach, 10 biologically and pharmaceutically relevant alkaloids were prepared using (R)-TRIP as the chiral catalyst: (R)-norcoclaurine, (R)-coclaurine, (R)-norreticuline, (R)-reticuline, (R)-trimemetoquinol, (R)-armepavine, (R)-norprotosinomenine, (R)-protosinomenine, (R)-laudanosine, and (R)-5-methoxylaudanosine.

Total synthesis of 8-epi-javaberine A and javaberine A

The total synthesis of berberine alkaloid javaberine A was examined. The B/C ring of berberine was successfully constructed by sequential Bischler-Napieralski cyclization-reduction protocols, and final demethylation afforded both javaberine A and its epimer.

Catalytic asymmetric synthesis of (S)-laudanosine by hydroamination

Lithium amide-chiral bisoxazoline-catalyzed asymmetric intramolecular hydroamination was examined with respect to the structural variants of starting aminoalkenes. Substituents on the nitrogen and olefin of aminoalkenes were found to be important factors affecting reaction efficiency as well as enentioselectivity in the production of chiral tetrahydroisoquinolines and isoindolines. The catalytic asymmetric total synthesis of (S)-laudanosine highlights the utility of the asymmetric hydroamination.

Enantioselective synthesis of tetrahydroprotoberberines and bisbenzylisoquinoline alkaloids from a deprotonated α-aminonitrile

Under controlled conditions, 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline- 1-carbonitrile can be quantitatively deprotonated in the α-position. Its alkylation directly furnishes 3,4-dihydroisoquinolines which can serve as starting materials for the preparation of various alkaloids. Here, the preparation of the benzylisoquinolines (+)-laudanidine, (+)-armepavine, and (+)-laudanosine as well as the tetrahydroprotoberberines ( - )-corytenchine and ( - )-tetrahydropseudoepiberberine using Noyori's asymmetric transfer hydrogenation are described. The dimeric alkaloids (+)-O-methylthalibrine and (+)-tetramethylmagnolamine were obtained from nonracemic precursors in Ullmann diaryl ether syntheses.

Method of Analyzing Optical Isomers or Method of Resolving the Same

Provided are a method of quickly and simply confirming the success or failure of resolution of optical isomers with the use of a column for resolving optical isomers and a method of simply designing the conditions of the eluent composition under isocratic elution conditions. In resolving optical isomers, the success or failure of the resolution can be simply and quickly confirmed by employing an HPLC gradient elution analysis method with the use of a column for resolving optical isomers. When the resolution is successfully conducted, the eluent composition under isocratic elution conditions can be estimated from the elution time in the gradient elution analysis.

Enantioselective synthesis of (+)-(S)-laudanosine and (-)-(S)-xylopinine

The study presents a new pathway for the enantioselective synthesis of benzylisoquinoline alkaloids. The key steps of the synthesis of (+)-(S)-laudanosine (1) and (-)-(S)-xylopinine (2) are a Sonogashira coupling that builds up the C1-C8a bond of the benzylisoquinoline skeleton, an intramolecular Ti-catalyzed hydroamination of an alkyne, and a subsequent enantioselective imine reduction according to Noyori's protocol.

Stereoselective synthesis of aporphine alkaloids using a hypervalent iodine(III) reagent-promoted oxidative nonphenolic biaryl coupling reaction. Total synthesis of (S)-(+)-glaucine

The aporphine alkaloid (+)-glaucine (8a) and two other analogues 8b,c have been synthesized in good yield and high ee from the appropriate 1,2-diarylethylamine derivatives, which were in turn prepared using (S)-(+)-phenylglycinol as chiral support. Next, a sequence of simple transformations: N-alkylation with bromoacetaldehyde diethyl acetal, N-methylation, Pommeranz-Fritsch cyclization, and ionic hydrogenation led to the key intermediate, optically active, 1-benzyltetrahydroisoquinolines 7a-c. The final C-ring closure step was performed by C-C biaryl bond formation by an hypervalent iodine(III) reagent promoted oxidative coupling, affording the target heterocycles 8a-c in good yields and with no racemization at the formerly created stereogenic center.

Chiral auxiliary mediated pictet-spengler reactions: Asymmetric syntheses of (-)-laudanosine, (+)-glaucine and (-)-xylopinine

Cyclohexyl-based chiral auxiliaries can be used effectively in an asymmetric Pictet-Spengler synthesis of tetrahydroisoquinoline, aporphine and protoberbine alkaloids. Using this strategy, concise asymmetric syntheses of (-)-laudanosine, (+)-glaucine and (+)- xylopinine have been accomplished.

General asymmetric synthesis of isoquinoline alkaloids. Enantioselective hydrogenation of enamides catalyzed by BINAP-ruthenium(II) complexes

In the presence of a small amount of RuX2[(R)- or (S)-BINAP] (X = anionic ligand) a wide range of (Z)-2-acyl-1-benzylidene-1,2,3,4- tetrahydroisoquinolines are hydrogenated to give the saturated products in nearly quantitative yields and in high (up to 100%) optical yields. The enamide substrates are selectively prepared by N-acylation of the corresponding 1-benzylated 3,4-dihydroisoquinolines under suitable acylation conditions; some crystalline materials having low solubility are obtained by a second-order Z/E stereomutation technique utilizing the double-bond photolability and lattice energy effects. This asymmetric hydrogenation sets the key stereogenic center in a predictable manner, either R or S flexibly, at the C(1) position of the benzylated tetrahydroisoquinolines. The chiral products are converted by standard functional group modification to tetrahydropapaverine, laudanosine, tretoquinol, norreticuline, etc. Hydrogenation of the simple 1-methylene substrate is used for synthesis of salsolidine. This enantioselective hydrogenation is applied to the synthesis of morphine and its artificial analogues such as morphinans and benzomorphans of either chirality. A mnemonic device is presented for predicting the reactivity and enantiofacial selection of the BINAP-Ru catalyzed hydrogenation. Reaction with BINAP-Rh catalyst proceeds with a lower enantioselectivity and an opposite sense of asymmetric induction.