Tazettine type alkaloids

Tazettine (CLXXIV R = OCH3, Ri = H, R2 = OH) is one of the more abundant of the Amaryllidaceae alkaloids, and structural studies on the base began more than thirty years ago (143). The degradative evidence cited in Volume VI for the structure of tazettine referred frequently to personal communications. Many of these data have been 

The configuration of the hydroxyl group at C-6a in CLXXIV is defined by the nature of the B D ring junction. Chemical evidence 

Macronine (mp 203°-205° [a] -j-413° in CHCI3) was isolated from Crinum macrantherum. Preliminary characterization indicated that the 

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Tazettine-type alkaloids derived from the [2]benzopyrano[3,4c]indole. 

Although tazettine (59) is one of the most widely distributed alkaloids in the Amaryllidaceae family, it was found to be an extraction artifact of pretazettine (61) (209). The presence of an A/-methyl group (2.4-2.5 ppm) in tazettine type alkaloids inmediately distinguishes them from the haemanthamine type, from which they proceed biosynthetically. Moreover the H NMR spectrum always shows the signal corresponding to the methylenedioxy group. 

The biosynthesis of lycorenine- and tazettine-type alkaloids cannot be accommodated within the concept of the phenyl-phenyl oxidative... 

Tazettine (62) is a widely reported alkaloid in the Amaryllidaceae family, particularly in Narcissus (see Tables VIII and IX), although it is known to be an extraction artifact of pretazettine (64) (75). All the alkaloids of the tazettine type that are isolated from Narcissus species show the typical methylenedioxy group between the C-8 and C-9 positions. Obesine (67) is an exceptional tazettine-type alkaloid with a seven-membered ring 76). 

Alkaloids of this type are the first example of the dinitrogenous-type Amaryllidaceae alkaloids, where the oxygen atom at the C6 in the tazettine-type alkaloids is replaced by a nitrogen atom, substituted with a pendant... 

The majority of the alkaloids that had affinity to the serotonin transporter (SERT) were crinine-type alkaloids. However, cherylline 4, tazettine 8 and 1-0-acetyllycorine 53 are the only alkaloids that showed affinity to SERT among the cheiylline-, tazettine- and lycorine-type alkaloids, respectively (80). The activity of the crinine-type alkaloids was attributed to the presence of a 1,3-dioxole moiety in common with the chnically used SSRI paroxetin (79). 

The alkaloids derived from 5,10b-ethanophenanthridine (crinine and haemanthamine types), 2-benzopyrano[3,4c]indole (tazettine type), phenanthridine (narciclasine type) and 5,11b-methanomorphanthridine (montanine type) originate from a para-para oxidative phenolic coupling (Fig. 9). 

It is well established that profiles of alkaloids vary with time, location, and developmental stage. In many instances, the site of biosynthesis is restricted to a single organ, but accumulation of the corresponding products can be detected in several other plant tissues. Long-distance transport must take place in these instances. There are only a few data on the ontogenic variations and distribution of alkaloids in species of the Amaryllidaceae family, and some results have been obtained in Narcissus species, such as N. assoanus (with only lycorine-type alkaloids) or N. confusus (with alkaloids of the homolycorine, hemanthamine, tazettine, and galanthamine types) 84,87). 

On the basis of recent phytochemistry investigation about Amaryllidaceae alkaloids, anew 12-type classificatimi, including (1) norbelladine type, (2) lycorine type, (3) homolycorine type, (4) crinine and haemanthamine types, (5) tazettine type, (6) montanine type, (7) pUcamine type, (8) graciline type, (9) galanthindole type, (10) galanthamine type, (11) phenanthridone and phenanthridine types, and (12) other minor species populations, are deduced according to their ring systems. Representative structures for each type of Amaryllidaceae alkaloids are shown in Tables 17.2-17.13. 

The photochemical reaction of tertiary amines with C6o can be used to synthesize alkaloid-C6o derivatives [269], Irradiation of alkaloids bearing a tertiary amino group such as tazettine, gramine, scandine, or 10-hydroxyscandine with C6o led to the isolation of alkaloid-C6o adducts. Use of tazettine and gramine in the reaction yielded the expected [6,6] adduct. In addition to the pyrrolidinofullerene 94a-b, a new type of monoadduct 95a-b with a bis-[6,6] closed structure characterized by UV-vis, FT-IR, II-NMR, 13C-NMR, II- II-COSY, ROESY, HMQC, and HMBC spectroscopy was obtained from the reaction with scandine 93a and its 10-hydroxy derivative 93b (Scheme 38). 

Details have appeared of the earlier very interesting report which showed that tazettine (3 R = OMe, = H) is an artifact produced from pretazettine (2 R = OMe, R = H) during isolation. This type of rearrangement can be carried out with basic reagents also and applies with identical implications to the criwelline (3 R = H, R = OMe) -precriwelline (2 R = H,R = OMe) relationship. The interconversion of alkaloids possessing a 5,10h-ethano-phenanthridine nucleus (4) with those of the aforementioned [2]benzopyrano-[3,4-c]indole type (3) has been reported. Carefully executed experiments show that variation in temperature, solvent, or pH is sufficient to alter the ring systems... 

Two examples for the formation of spirocycUc structures are presented in Scheme 24. The first one is a key step in the enantioselective total synthesis of the alkaloid (+)-tazettine.f The second is the result of a domino process with two subsequent carbopalla-dation steps numerous examples of this type of donfino process are found in the literature and are discussed in other sections of this compendium. 

The large number of structurally diverse Amaryllidaceae alkaloids are classified mainly into nine skeleton types, for which the representative alkaloids are norbelladine, lycorine, homolycorine, crinine, hemanthamine, narciclasine, tazettine, montanine, and galanthamine (Fig. 1). With the aim of unifying the numbering system of the different skeleton types, Ghosal s model will be used in this review (20). 

Skeleton types LY, lycorine FIL, homolycorine HT, hemanthamine TZ, tazettine NC, narcielasine MN, montanine GA, galanthamine OA, other alkaloids. Alkaloid names see Tables I-VII. 

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