Alkaloids tetrahydroquinoline

The [4+2] intramolecular cyclization of or/ o-substituted chloromethylanilides has led to the synthesis of the tetrahydroquinoline alkaloid virantmycin (Scheme 68) <2006EJ04916>. 

The spectrum of the tetrahydroquinoline alkaloid calycanthine has been discussed in connection with the investigation of some indoline alkaloids.80... 

Root cultures of Menispermum dauricum DC. have yielded several chlorinated alkaloids, the most recent of which are dauricumine (108) and dauricumidine (109) [94,95]. The tetrahydroquinoline alkaloid virantmycin (110) is produced by Strepto-myces nitrosporeus [96,97], as is benzastatin C (111) [98]. 

Virantmycin is a tetrahydroquinoline alkaloid that has inhibitory activity against DNA and RNA viruses. A total synthesis of virantmycin making use of a key type II aziridine has elucidated the absolute stereochemistry at C-2 and C-3 <1996T10609>. An intramolecular photocyclization of an azide onto a Z-alkene produces type II aziridine 351 in excellent yield. A three-step reduction/selective reoxidation procees yields key aziridine alcohol 352 in 76% overall yield (Scheme 71). The alcohol is methylated and the ester hydrolyzed without harm to the azirdine. A TFA-induced ring opening of the aziridine by chloride provides the natural product virantmycin in good yield. This entire process was also carried out with the -alkene to produce /)(-virantmycin, thus proving the stereochemistry at C-2 and C-3. 

These couplings are of major importance in the alkaloid area, where they may be biomimetic, and there has been a considerable quantity of work on the 1-benzyl- and 1-phenylethyl-tetrahydroquinoline alkaloids, which has been reviewed. ... 

Scheme 10.17 Asymmetric synthesis of tetrahydroquinoline alkaloids and drug.

Asymmetric hydrogenation of quinolines activated by chloroformates also pro vided a convenient route to synthesize optically active tetrahydroquinoline alkaloids (Scheme 10.23). They also applied this methodology to total synthesis of some alkaloids [31]. For instance, reduction ofhydrogenation products with LiA]H4 in Et2O gives the N methylation products in high yields, which are the naturally occurring tetrahydroquinoline alkaloids. 

The benzastatin family and virantmycin are a novel class of indoline and tet-rahydroquinoline alkaloids isolated from Streptomyces nitrosporeous. Benzastatins show inhibitory activity against glutamate toxicity and lipid peroxidation in rat liver microsomes that can be used to prevent brain ischemia injury, and consists of indoline alkaloids such as benzastatin E, and tetrahydroquinoline alkaloids such as benzastatin C that are structurally related to virantmycin. (—)-Virantmycin, a... 

The Fustero group recently also applied this strategy for the enantioselective total synthesis of (-i-)-angustureine (308) 289). (Scheme 70) Angustureine (308) is a tetrahydroquinoline alkaloid isolated from the bark of the Venezuelan shrubby tree Galipea officinalis 291). Carrying out the iminium-catalyzed intramolecular... 

Scheme 96 Chiral phosphoric acid-catalyzed transfer hydrogenation in the syntheses of different biologically active tetrahydroquinoline alkaloids...

Jacquemond-Collet I, Hannedouche S, Fabre N, Fouraste I, Moulis C (1999) Two Tetrahydroquinoline Alkaloids from Galipea officinalis. Phytochemistry 51 1167... 

A volatile tetrahydroquinoline alkaloid named fabianine (Fig. 5.1) was identified from the aerial part of Fabiana imbricata Ruiz Pav. (Edwards and Elmore 1962). This base is a congener of bicychc, cadinene/norcadinene type sesquiterpenes (see Sect. 7.3.1). Fabianine seems to share a common precursor with a monocyclic (A-free) diketonorcadinene type metabolite. Thus, it may be assumed that the structure of fabianine is characterized by a sesquiterpenoid skeleton (Schmeda-Hirschmann and Papastergiou 1994). 

Biologically active tetrahydroquinoline alkaloids 15 were prepared by simple N-methylation of intermediates 14 to lead the desired natural products in good overall yields and high enantioselectivities (for examples of dual catalysis, see [80,81], for more recent examples, see [82-84]). 

Scheme 4 Syntheses of biologically active tetrahydroquinoline alkaloids 15...

Quinoline-4-carbaldehyde derivatives also occur in higher plants (Table Vlll). For example, 8-hydroxyquinoline-4-carbaldehyde oxime (J.3.1 Scheme 9) was isolated from Broussonetia zeylanica (Moraceae) (151-153). (+)-Tuberosine B (J.1.2), an unprecedented tetrahydroquinoline alkaloid, has been reported in the inaccessible Chinese literature as a new metabolite of Allium tuberosum (Alliaceae) (157). Eichhornia crassipes (Pontederiaceae) is an invasive plant and often jams rivers and lakes with uncounted thousands of tons of floating plant matter. It has yielded 1,4-dimethylquinolinium iodide (J.4) (142). 

SCHEME 30.45. Ir-catalyzed asymmetric hydrogenation of quinoline-heterocycle in the s3mthesis of tetrahydroquinoline alkaloids. 

Discovered in 1991 in the species Clavdina lepadiformis harvested near the island of Helgoland (North Sea), lep-adin A is the first example of ds-tetrahydroquinoline alkaloid isolated from a marine organism (Steffan,... 

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