4747-98-2

Usage

Uses

Used in Pharmaceutical Industry:
(S)-(-)-Tetrahydropapaverine is used as a key intermediate in the enantioselective synthesis of various alkaloids and pharmaceuticals, such as (+)-(S)-Laudanosine (L178525) and (-)-(S)-Xylopinine. Its unique stereochemistry allows for the development of enantiomerically pure compounds, which are essential for the production of effective and safe medications.
Used in Enantioselective Synthesis:
(S)-(-)-Tetrahydropapaverine is used as a chiral building block in the enantioselective synthesis of biologically active compounds. Its presence in the synthesis process ensures that the desired enantiomer is selectively produced, leading to more effective and targeted therapeutic agents.

Upstream product

• 13074-31-2 Tetrahydropapaverine 
• 21852-32-4 4-bromomethyl-1,2-dimethoxybenzene 
• 90482-03-4 6,7-dimethoxy-1,2,3,4-tetrahydro-2-[(1-tert-butoxy-3-methyl)-2-butyliminomethyl]isoquinoline 
• 97157-25-0 2-Benzoyl-1-<(3,4-dimethoxyphenyl)methyl>-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 
• 57651-56-6 (S)-1-<(3,4-Dimethoxyphenyl)methyl>-2-formyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 
• 114105-61-2 (S)-1-(3,4-Dimethoxy-benzyl)-6,7-dimethoxy-2-((R)-1-phenyl-ethyl)-1,2,3,4-tetrahydro-isoquinoline 
• 121443-94-5 (S)-2-[(S)-1-(2-Chloro-phenyl)-ethyl]-1-(3,4-dimethoxy-benzyl)-6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline 
• 121443-98-9 1-(3,4-Dimethoxybenzyl)-2-<(1S)-1-(2,6-dichlorophenyl)ethyl>-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 
• 860-23-1 (S)-2-Acetyl-1-<(3,4-dimethoxyphenyl)methyl>-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 
• 154013-16-8 (S)-2-(p-Bromobenzoyl)-1-<(3,4-dimethoxyphenyl)methyl>-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 
• 102922-34-9 2-[(4S)-4,5-dihydro-4-(1-methylethyl)-2-oxazolyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 
• 7306-46-9 4-chloromethyl-1,2-dimethoxy-benzene 
• 178422-15-6 (S)-2-[(S)-1-(3,4-Dimethoxy-benzyl)-6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl]-2-phenyl-ethanol 
• 6957-27-3 3,4-dihydropapaverine 

Downstream Products

• 64229-38-5 (RS)/meso-N,N'-4,7-dioxa-3,8-dioxodecylene-1,10-diyl-bis-tetrahydropapaverine 
• 2688-77-9 (S)-laudanosine 
• 523-02-4 (S)-(-)-norcoralydine 
• 145487-46-3 (+)-N,N'-4,11-dimethyl-4,11-diaza-3,12-dioxotetramethylene-1,14-diyl-bis(S)-tertahydropapaverine 
• 57651-56-6 (S)-1-<(3,4-Dimethoxyphenyl)methyl>-2-formyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 
• 1344118-31-5 (S)-(+)-1-(2-bromo-4,5-dimethoxybenzyl)-2-formyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 
• 4829-34-9 (S)-(+)-1-(2-bromo-4,5-dimethoxybenzyl)-2-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 
• 50720-57-5 (S)-(-)-norlaudanosine (-)-N-acetyl-L-leucine 
• 64493-09-0 (RS)/meso-N,N'-4,10-dioxa-3,11-dioxotridecylene-1,13-diyl-bis-tetrahydropapaverine 
• 64229-34-1 N,N'-4,7-dioxa-3,8-dioxodecylene-1,10-diyl-bis-(S)-(+)-tetrahydropapaverine 

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.

Biosynthesis of plant tetrahydroisoquinoline alkaloids through an imine reductase route

Herein, we report a biocatalytic approach to synthesize plant tetrahydroisoquinoline alkaloids (THIQAs) from dihydroisoquinoline (DHIQ) precursors using imine reductases and N-methyltransferase (NMT). The imine reductase IR45 was engineered to significant

Synthesis of Tetrahydroisoquinoline Alkaloids and Related Compounds through the Alkylation of Anodically Prepared α-Amino Nitriles

α-Amino nitrile 2a was conveniently prepared in two individual steps from chiral hexafluorophosphate salt isoquinolinium (-)-8b including anodic cyanation as an efficient means to activate the sp3 C1-H bond of the THIQ nucleus. The lithiation o

Efficient and Practical Syntheses of Enantiomerically Pure (S)-(-)-Norcryptostyline I, (S)-(-)-Norcryptostyline II, (R)-(+)-Salsolidine and (S)-(-)-Norlaudanosine via a Resolution-Racemization Method

Four racemic tetrahydroisoquinolines (RS)-(±)-1-4 were prepared from homoveratrylamine via amidation, Bischler-Napieralski reaction and the subsequent reduction. The enantiomerically pure tetrahydroisoquinolines (S)- (-)-norcryptostyline I [(S)-(-)-1], (S)-(-)-norcryptostyline II [(S)-(-)-2], (R)-(+)-salsolidine [(R)-(+)-3] and (S)-(-)-norlaudanosine [(S)-(-)-4] were then obtained in 45%, 40%, 41% and 38% yields, respectively, via resolution of the racemic compounds (RS)-(±)-1-4 with half equivalent of chiral acids. In addition, the enantiomerically enriched compounds (R)-(+)-1, (R)-(+)-2, (S)-(-)-3 and (R)-(+)-4 from the mother liquors were efficiently racemized via a one-pot redox method in almost quantitative yields.

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.

Asymmetric synthesis of (S)-(-)-xylopinine. Use of the sulfinyl group as an ipso director in aromatic SE

Optically pure (S)-(-)-xylopinine 2 was prepared in three steps in 52% overall yield. Thus, condensation of the carbanion derived from (S)-4 with the (S)-(E)-sulfinylimine 5 gave a 2:1 mixture of tetrahydroisoquinolines 6a and 6b, differing only in configuration at sulfur. N-Desulfinylation of this mixture gave the diastereomeric sulfoxides which, without separation, were converted into (S)-(-)-xylopinine (2) with loss of the sulfinyl moieties under Pictet-Spengler conditions. This unprecedented ipso electrophilic substitution of a sulfinyl group may have synthetic implications beyond that described in this work.

Synthesis of (-)-(S)-norlaudanosine, (+)-(R)-O,O-dimethylcoclaurine, and (+)-(R)-salsolidine by alkylation of an α-aminonitrile

A short asymmetric synthesis of 1-substituted 1,2,3,4- tetrahydroisoquinoline alkaloids by deprotonation of an unprotected α-aminonitrile and alkylation of the resulting carbanion followed by spontaneous elimination of HCN and asymmetric reduction is described. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.

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.

Asymmetric reduction of prochiral cyclic imines to alkaloid derivatives by novel asymmetric reducing reagent in THF or under solid-state conditions

Asymmetric reductions of prochiral cyclic imines were studied using chiral nonracemic sodium acyloxy borohydride 2. The chiral nonracemic reducing agent 2 has been easily prepared by the reaction of NaBH4 with N,N- phthaloyl amino acid 1 in THF

Enantioselective catalytic reduction of dihydroisoquinoline derivatives

Thiazazincolidine complexes, 2, were shown to be excellent catalysts for enantioselective reduction of dihydroisoquinolines 1 with BH3 · THF to the corresponding amines in good ee.